Home Medicine Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
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Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells

  • Shengyou Song , Lunwei Tai , Lei Zhou , Junling Jiang and Junfeng Zhao EMAIL logo
Published/Copyright: February 4, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Objective

To investigate how lathyrol affects aggressive behaviors and related proteins of the androgen receptor (AR) 786-O cells.

Methods

786-O cells were cultured in vitro and divided into these groups at random: the dimethylsulfoxide (DMSO) control group (A group), negative control group (B group), and experimental group (C group). Cells in A group were grown in DMSO working medium (contained RPMI 1640 medium and 1% DMSO), B group cells were cultured in nilutamide working medium (contained DMSO working medium and 325 μg/mL nilutamide), while those in C group were cultured in lathyrol working medium (contained DMSO working medium and 300 μg/mL lathyrol). Cell proliferation was measured via CCK-8 assays, and cell apoptosis was examined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Scratch tests and Transwell invasion tests were used to evaluate cell movement and penetration. The expression information about p-AR, AR, p-Akt, ki67, caspase3, cleaved-caspase3, Bcl-2, Bax, caspase9, cleaved-caspase9, and GAPDH proteins was investigated through western blotting. Immunocytochemistry was used to identify the 786-O cells’ secretion level of matrix metalloproteinase 2 (MMP2), MMP9, and prostate-specific antigen (PSA) proteins.

Results

The negative control and experimental groups’ cells exhibited reduced proliferation, migration, and invasion and increased apoptosis after 24 h treatment. Furthermore, these two group cells exhibited a notable reduction in the status of Ki67, Bcl-2, MMP2, MMP9, and p-Akt (P < 0.05) and significantly increased the expressions of AR, p-AR, Bax, cleaved-caspase3, and cleaved-caspase9 (P < 0.05). There was no statistical distance in PSA, caspase3, and caspase9 expressions among the three groups (P > 0.05).

Conclusion

In vitro, lathyrol and nilutamide exert notable anticancer effects by effectively suppressing the proliferation, migration, and invasion of 786-O cells while also inducing apoptosis.

Keywords: lathyrol; renal cell cancer; androgen receptor; malignant behavior of tumor cells

1 Introduction

Renal cell carcinoma (RCC) is a prevalent form of tumor in the urinary tract that comprises approximately 3% of the malignant tumors in adults [1]. RCC is the second most common urological tumor. Despite having a lower occurrence than prostate cancer (PCa), RCC exhibits the undesirable fatality rate among malignant neoplasm diseases that impact the urinary system and the prognosis of RCC patients is more severe than that of PCa patients and bladder cancer patients [2,3]. In view of this, it is urgent to find more effective targeted therapies for RCC.

In recent years, the androgen receptor (AR) has become a crucial focus for the cancer therapy. AR is a crucial focus not just in urological cancers, but also in the management of various other types of tumors [4–6]. Most primary and metastatic PCa tumors show AR expression, which is closely linked to PCa advancement [7,8] and tumorigenesis [9]. Due to the grim prognosis and survival rate of RCC patients [10,11], there is an imperative necessity to explore innovative diagnostic and therapeutic approaches for these patients. Research on immune-targeted strategies acquires growing focus in the RCC diagnosis and treatment [12–15]. Traditional Chinese medicines (TCM) offer more cost-effective advantages and less adverse reactions compared to conventional clinical medications. The TCM has the ability to both eliminate tumor cells and prevent cancer by boosting the immune system and health conditions of patients [16–18]. Latterly, the compatibility between TCM and clinical anticancer drugs has been recognized, leading to more effective cancer cell killing and improvements in clinical cancer diagnosis, treatment, postoperative recovery, and prognosis [19–21]. Meanwhile, we found that the lathyrol exhibits tumor suppressive activity against a variety of tumor types by acting on multiple target proteins and several mechanisms. This finding provides a more effective and feasible alternative treatment option for patients with tumors that cannot be treated via surgery operations. Currently, whether lathyrol can affect the biological function of human RCC cells-786-O via affecting AR-related proteins expression is unknown and has not been researched. Hence, we investigated the influences of lathyrol on the malignant activity of 786-O cells through the modulation of AR and prostate-specific antigen (PSA) expression, thereby revealing the antitumor mechanism of lathyrol.

2 Materials and methods

2.1 Major materials

The following reagents and materials were used in this study: 786-O human RCC cell line authenticated by RTS (Short Tandem Repeat) authentication and mycoplasma tests (Procell Life Science & Technology Co., CL-0010); lathyrol (Weikeqi-Biotech, Sichuan, China, Wakq-00424); nilutamide (AR blocker; Abmole Biotechnology Co., Ltd); fetal bovine serum (FBS; Absin Bioscience); CCK-8 reagent and phosphate buffer saline (PBS) buffer (Biosharp); 1640 basal medium, trypsin-ethylene diamine tetraacetic acid (0.25%) digestion solution, cell culture-grade dimethylsulfoxide (DMSO), tissue and cell radio-immunoprecipitation assay (RIPA) lysis buffer, phenylmethanesulfonyl fluoride, goat serum, hydrogen peroxide (H2O2), Mayer’s hematoxylin staining solution, crystal violet staining solution, and neutral balsam (Solarbio); enhanced chemiluminescence (ECL) developing solution, horse radish peroxidase (HRP)-labeled sheep anti-rabbit secondary antibody for immunohistochemistry, and diaminobenzidine (DAB) chromogenic kit (Servicebio); bicinchoninic acid assay (BCA) protein quantification kit, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) cell apoptosis detection kit (green fluorescence), Triton X-100 (cell permeabilization agent), 4′,6-diamidino-2-phenylindole nuclear stain, mounting medium with anti-fluorescence quenching reagent, and HRP-labeled goat anti-rabbit secondary antibody (Beyotime Biotechnology); 6-well Transwell plates and Matrigel (Corning Biotechnology); rabbit polyclonal anti-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antibody (internal control; Hangzhou Xianzhi Biotechnology); rabbit polyclonal anti-Ki67 antibody (Bioss Biotechnology); 4% paraformaldehyde fixative solution and anti-phosphorylated adrenergic receptor (p-AR) antibody (phosphorylation site, S650; Absin Biotechnology); protein marker (10–180 kD), anti-phosphorylated Akt (p-Akt) antibody (phosphorylation site, Ser473), rabbit polyclonal anti-Bax antibody, anti-Bcl-2 antibody, anti-matrix metalloproteinase 2 (MMP2) antibody, anti-MMP9 antibody, and anti-cleaved-caspase3 & caspase3 antibody (Wuhan Sanying Biotechnology); rabbit polyclonal anti-AR antibody and rabbit monoclonal anti-cleaved-caspase9 & caspase9 antibody (Affinity Biotechnology); and rabbit monoclonal anti-PSA antibody (STARTER Biotechnology).

2.2 Methods

2.2.1 Cell culture

786-O cells were regularly grown at constant-temperature cell incubator (with 37°C, 5% CO2, and 95% humidity) in cell culture medium (contained RPMI 1640 medium, 10% FBS, and 1% penicillin and streptomycin). When the cells reached about 85% confluence on the culture flask surface, the cells in the logarithmic phase of growth were digested and utilized in the subsequent experiments.

2.2.2 Experimental grouping

First, we added 1% DMSO to the medium and performed a contrast experiment. The results showed that the effect of DMSO on the cell viability of 786-O cells cultured in normal medium was not significantly different from that of 786-O cells cultured in normal medium. Therefore, we used this group as the DMSO control group. Moreover, an experimental plan was developed to precisely determine the minimum drug concentration required for nilutamide and lathyrol to exert the maximum anticancer effect, and this concentration was used as the standard concentration for subsequent experiments to further explore the anticancer efficacy of these two drugs. Therefore, based on the results of preliminary experiments (Figure 1a and b), 786-O cells were divided into three groups at random: the DMSO control group (A group), negative control group (B group), and experimental group (C group), and the appropriate drug concentration for each group was determined. Cells in A group were grown in DMSO working medium (contained RPMI 1640 medium and 1% DMSO), B group cells were cultured in nilutamide working medium (contained DMSO working medium and corresponding nilutamide drug concentrations), while those in C group were cultured in lathyrol working medium (contained DMSO working medium and corresponding lathyrol drug concentrations).

Figure 1 CCK-8 assay was utilized to figure out the diverse drug concentrations used for subsequent experiments. (a) Concentrations of lathyrol used for subsequent experiments and (b) nilutamide concentrations used for the same purpose. The model group cells, which were not treated, were cultured in cell culture medium. For the remaining groups, the drugs were added to the medium at specific concentrations such that the DMSO level did not exceed 1%. The results obtained for the model group compete with the DMSO control group, and the results obtained for the remaining drug concentrations treatment group were compared with A group. According to above CCK8 results, the concentration gradient function was established, and the IC75, IC50, and IC25 values of lathyrol against 786-O cells were 340.86, 293.72, and 202.66 μg/mL. The IC75, IC50, and IC25 values of nilutamide against 786-O cells were 282.54, 293.72, and 47.10 μg/mL.
Figure 1

CCK-8 assay was utilized to figure out the diverse drug concentrations used for subsequent experiments. (a) Concentrations of lathyrol used for subsequent experiments and (b) nilutamide concentrations used for the same purpose. The model group cells, which were not treated, were cultured in cell culture medium. For the remaining groups, the drugs were added to the medium at specific concentrations such that the DMSO level did not exceed 1%. The results obtained for the model group compete with the DMSO control group, and the results obtained for the remaining drug concentrations treatment group were compared with A group. According to above CCK8 results, the concentration gradient function was established, and the IC75, IC50, and IC25 values of lathyrol against 786-O cells were 340.86, 293.72, and 202.66 μg/mL. The IC75, IC50, and IC25 values of nilutamide against 786-O cells were 282.54, 293.72, and 47.10 μg/mL.

2.2.3 Assessment of cell proliferation ability by the CCK8 assay

786-O cells in the exponential phase of growth were plated in 96-well culture plates at a concentration of 8 × 103 cells/mL (100 μL per well). After cell attachment, 100 μL of 1640 medium with the appropriate drug concentration was added and cultured for 24 h. At specified intervals, 10 μL of CCK-8 reagent was uniformly mixed into the medium in each well, and the cells were further incubated at 37°C for an additional 3.5 h in an incubator saturated with 5% CO2. Using a microplate reader to measure the absorbance at 450 nm, the culture medium served as a blank control for determining cell viability. The percentage of cell viability (%) = [(AS − Ab)/(Ac − Ab)] × 100%.

2.2.4 TUNEL staining detect cell apoptosis

The cells were immersed in 75% alcohol for 20 min, washed three times with 1× PBS, and placed in 6-well plates, with three replicates for each group. 786-O cells were placed in 6-well culture plates at a seeding density of 1 × 105 cells/mL. Three replicates of each group were included. Once the cells had adhered and reached 80% confluence in the 6-well culture dishes, the media was supplemented with RPMI 1640 medium containing the appropriate drugs for 24 h. 786-O cell apoptosis was evaluated strictly following the guidelines provided with the TUNEL apoptosis detection kit. Nuclei and/or cell debris of apoptotic cells emitted green fluorescence, and nuclei of nonapoptotic cells emitted blue fluorescence. The changes in the fluorescence of 786-O cell nuclei were observed under a fluorescence microscope. The average value was calculated by randomly selecting three high-power fields for each group. The apoptosis fluorescence intensity (AFI) was quantitatively analyzed using ImageJ as follows: AFI = (area of apoptosis green fluorescence in the field of view/area of the nucleus in the field of view).

2.2.5 Scratch assay for the assessment of the cell migration ability

786-O were plated in 6-well culture plates at a density of 1 × 105 cells/mL (with three replicates of each group). Once the cells had adhered and reached 90% confluence in the 6-well culture plate, the old 1640 medium was replaced with fresh medium, and the cells were incubated for 12 h. A sterile 10 μL pipette tip was used to vertically scratch the cell monolayer, after which the medium was removed, and the scratched cells were washed with 1× PBS. 1640 medium with a suitable drug concentration was added to each well. The cells were placed in an incubator with a temperature of 37°C and 5% CO2 for a duration of 24 h. Subsequently, the width of the scratch was carefully examined and captured using a high-powered magnifying lens. Cell migration index (%) was calculated at follows: cell migration distance at 24 h/cell migration distance at 0 h × 100%.

2.2.6 Detection of cell invasion ability using a Transwell chamber

The same drug treatment was applied to the cells as described for the scratch assay. After treatment for 24 h, the cells were digested via trypsin and subsequently transferred to Transwell plates. Prior to cell addition, the 6-well plate and Transwell chamber were immersed in 1× PBS for 5 min to moisten the chamber. Subsequently, 80 µL of Matrigel was introduced into the chamber, and the chamber was incubated at 37°C for 30 min to allow the gel to solidify. 786-O cells were subsequently diluted in serum-free 1640 medium to a concentration of 4 × 104 cells/mL. For each group, triplicate wells were established by adding 2 mL cell culture medium (contained RPMI 1640 medium and 10% FBS) to the lower chamber after cell seeding (1 mL of cell suspension) in the upper chamber. The cells were incubated at 37°C for 24 h. After the 24 h culture period, the cells located on the upper chamber surface (specifically, cells that had not penetrated into the lower chamber) were delicately eliminated using a cotton swab. After fixation in 4% paraformaldehyde for 15 min, the cells that had entered the lower chamber were stained with 0.25% crystal violet for 30 min and then observed using a microscope. ImageJ software was used to count the number of cells that invaded the lower chamber in randomly selected low-power and high-power fields, which included the central and peripheral membranes.

2.2.7 Western blot analysis of the expression of Ki67, Bcl-2, Bax, caspase9, cleaved-caspase9, caspase3, cleaved-caspase3, AR, p-AR, and p-Akt in cells

After 24 h of the same treatments used for the scratch assay, the cells were enzymatically digested with trypsin and subsequently transferred to a 1.5 mL centrifuge tube. The tube was then centrifuged at a speed of 12,000 rpm for 10 min. Proteins were extracted by lysing the cells in ice-cold RIPA lysis buffer. BCA assay was used to determine the concentration of the proteins. Following SDS‒PAGE, the proteins were transferred to polyvinylidene fluoride membranes, and the membranes were subsequently blocked using tris buffered saline tween (TBST) (including 5% skim milk powder) and incubated overnight at 4°C on a shaker with primary antibodies diluted in TBST (including 5% skim milk powder). The dilutions used for the AR, proliferation and apoptosis related protein antibodies are shown in Table 1. Afterward, the membranes were placed on a shaker and incubated with TBST (containing 5% skim milk powder) diluted with HRP-labeled secondary antibodies at room temperature for 2.5 h. Subsequently, the membranes were incubated with ECL reagent. The bands were scanned, and the gray values of the bands were quantitatively analyzed by ImageJ software.

Table 1

Primary antibody dilutions for WB

Primary antibody Dilution ratio
AR 1:1,000
p-AR 1:1000
Ki67 1:1,000
Bax 1:5,000
Bcl-2 1:5000
p-Akt 1:5,000
Caspase3 1:1,000
Caspase9 1:1,000
GAPDH (internal reference) 1:1,000

2.2.8 Evaluation of the expression of MMP2, MMP9, and PSA in cells by immunocytochemistry (ICC)

Coverslips (20 mm) were soaked in 75% alcohol for 20 min, washed three times with 1× PBS, and placed in 6-well plates. The cells were distributed at a concentration of 1 × 105 cells/mL in 6-well culture plates, with three replicates for each group. The treatments used were the same as those used in the scratch assay. After 24 h, the medium containing the drug was removed, and the cells were rinsed twice with 1× PBS and then immersed in 1 mL of 4% paraformaldehyde for 15 min. Subsequently, the coverslips were carefully placed onto glass slides using tweezers. Following permeabilization using %Triton X-100 (diluted in 1× PBS) for 5 min at ambient temperature, 3% H2O2 was gradually introduced into the cells to inhibit their natural peroxidase activity. Subsequently, the cells were maintained at room temperature for 30 min. To block nonspecific binding, goat serum working solution was subsequently added dropwise to the cells, and the cells were then incubated for 30 min at room temperature. After dilution of the primary antibodies (the dilution ratios are shown in Table 2), the cells were incubated in a wet box at 4°C overnight, and the antibodies were then added dropwise. The cells were subsequently subjected to three 3 min washes with PBS and then dried with absorbent paper. Next, a goat anti-rabbit secondary antibody conjugated to HRP (at a dilution ratio of 1:300) was added, and the samples were incubated at room temperature for 30 min. Freshly prepared DAB chromogenic solution was added dropwise, and nuclear counterstaining was performed with Mayer hematoxylin. The slides were mounted using neutral balsam, and the average optical density (AOD) was quantified using ImageJ software.

Table 2

Primary antibody dilutions for immunocytochemistry

Primary antibody Dilution ratio
MMP2 1:100
MMP9 1:100
PSA 1:200

2.3 Statistical analysis

Cells are divided into three groups. A group is the DMSO control group, B group is the negative control group, and C group is the experimental group. The data were analyzed using IBM SPSS 26.0, and the figures were generated using GraphPad Prism 9.5. All cell experiments were proceeded with triplicated independent biological replicates. A difference was considered statistically significant if P < 0.05, *P < 0.05, **P < 0.01, or ***P < 0.001; alternatively, a difference is considered not significant if P > 0.05.

3 Results

3.1 Lathyrol inhibited the proliferation of 786-O human RCC cells

After a 24 h treatment period, the viability of 786-O cells in both the B and C groups exhibited a significant reduction (Figure 2c). Additionally, the secretion levels of the Ki67 protein were diminished in comparison to the 786-O cells in group A (Figure 2a). This finding suggests that both lathyrol and nilutamide demonstrate substantial inhibitory effects on the proliferative capacity of RCC 786-O cells. Notably, the proliferative potential of 786-O cells in the negative control, as well as in the experimental B and C groups, was significantly lower than that observed in the DMSO control group A (P < 0.05). Furthermore, the expression level of Ki67 in the experimental groups was significantly reduced compared to the other two groups (P < 0.05). However, no statistically significant difference was found in Ki67 expression between the negative control and DMSO control groups B and C (P > 0.05).

Figure 2 (a) Western blot results for Ki67 and GAPDH protein expression, (b) statistical analysis of Ki67 expression levels, and (c) statistical analysis of the CCK-8 results. The numerical details can be seen in Figure 10a(a) and (b).
Figure 2

(a) Western blot results for Ki67 and GAPDH protein expression, (b) statistical analysis of Ki67 expression levels, and (c) statistical analysis of the CCK-8 results. The numerical details can be seen in Figure 10a(a) and (b).

3.2 Lathyrol promoted the protein expression of Bcl-2, cleaved-caspase3, and cleaved-caspase9 and inhibited the protein expression of Bax in 786-O cells

Under the treatment, the apoptosis of 786-O cells was enhanced. In particular, both lathyrol and nilutamide exhibited a pronounced capacity to significantly facilitate the apoptotic process in 786-O cells. As illustrated in Figure 3, the DMSO control group (Group A) demonstrated elevated levels of Bcl-2 protein expression alongside diminished levels of Bax, cleaved-caspase3, and cleaved-caspase9 protein expression when compared with the control groups B and C. Additionally, the negative control group B and the experimental group C showed considerably increased expression levels of Bax, cleaved-caspase3, and cleaved-caspase9, while also exhibiting reduced Bcl-2 protein expression in comparison to the DMSO group (P < 0.05). However, no statistically significant differences were observed in the expression levels of caspase3 and caspase9 among the three groups (P > 0.05).

Figure 3 (a) Western blot results are presented for the protein expression of Bcl-2, Bax, and GAPDH. (b) Western blot results for caspase3, cleaved-caspase3, and GAPDH expression. (c) Western blot results for caspase9, cleaved-caspase9, and GAPDH expression. (d) Statistical analysis for Bcl-2 expression. (e) Statistical analysis for caspase3 expression. (f) Statistical analysis for caspase9 expression. (g) Statistical analysis for Bax expression. (h) Statistical analysis for cleaved-caspase3 expression. (i) Statistical analysis for cleaved-caspase9 expression. The numerical details can be seen in Figure 10a(c)–(h).
Figure 3

(a) Western blot results are presented for the protein expression of Bcl-2, Bax, and GAPDH. (b) Western blot results for caspase3, cleaved-caspase3, and GAPDH expression. (c) Western blot results for caspase9, cleaved-caspase9, and GAPDH expression. (d) Statistical analysis for Bcl-2 expression. (e) Statistical analysis for caspase3 expression. (f) Statistical analysis for caspase9 expression. (g) Statistical analysis for Bax expression. (h) Statistical analysis for cleaved-caspase3 expression. (i) Statistical analysis for cleaved-caspase9 expression. The numerical details can be seen in Figure 10a(c)–(h).

3.3 Lathyrol promoted the apoptosis of 786-O cells

The TUNEL test revealed that the DNA fragmentation of 786-O cells in groups B and C was more pronounced (Figure 4a). Concurrently, the AFIs of 786-O cells in groups B and C were more significant than those in group A (Figure 4b). Importantly, both lathyrol and nilutamide markedly enhance the apoptosis of 786-O cells. The findings are illustrated in Figure 4. The negative control B group and the experimental C group demonstrated significantly elevated AFIs and a notably higher fluorescence intensity compared to the DMSO control A group (P < 0.05).

Figure 4 (a) Outcomes of the TUNEL staining of 786-O cells in different groups following medication. (b) Statistical evaluation of the AFIs in each group. The numerical details can be seen in Figure 10b(a).
Figure 4

(a) Outcomes of the TUNEL staining of 786-O cells in different groups following medication. (b) Statistical evaluation of the AFIs in each group. The numerical details can be seen in Figure 10b(a).

3.4 Lathyrol inhibited the migration of 786-O cells

The results of scratch experiment showed (Figure 5a) that 786-O cells in group A could almost completely fill the scratch wound, while the migration ability of 786-O cells in groups B and C was significantly inhibited, leaving significant scratch gaps. In addition, a significant inhibitory effect of lathyrol and nilutamide on cell migration ability was also observed. In addition, the cells in the B and C groups had a reduced migration distance and lower cell migration rate compared to A group, with statistical significance (P < 0.05).

Figure 5 (a) Images of the scratch assay of 786-O cells in each group after drug treatment. (b) Statistical analysis of the cell migration rate of each group. The numerical details can be seen in Figure 10b(b).
Figure 5

(a) Images of the scratch assay of 786-O cells in each group after drug treatment. (b) Statistical analysis of the cell migration rate of each group. The numerical details can be seen in Figure 10b(b).

3.5 Lathyrol inhibited the invasion of 786-O cells

Transwell experiment results (Figure 6a) demonstrate that at low magnification, the quantity of cells that infiltrated the Matrigel in both the negative control and experimental groups was notably less than 786-O cells in the A group; at high magnification, the number of cells that infiltrated the Matrigel in the A group was meaningfully greater than the other groups (P < 0.05). There was no notable statistical distinction observed between the B and C groups. Hence, lathyrol and nilutamide exhibit a marked inhibitory effect on the invasive capacity of 786-O cells.

Figure 6 (a) Outcomes of the Transwell tests on 786-O cells in different groups following medication; ((a) depicts the findings of the Transwell invasion test under low magnification (×100); while (b) illustrates the results of the Transwell invasion test under high magnification (×200). Cells that moved across the Transwell membrane were colored in a blue-purple hue using crystal violet staining solution). (b) Statistical analysis of cell migration through the Transwell membrane in each group at low magnification. (c) Statistical analysis of cell migration through the Transwell in each group at high magnification. The numerical details can be seen in Figure 10b(c) and (d).
Figure 6

(a) Outcomes of the Transwell tests on 786-O cells in different groups following medication; ((a) depicts the findings of the Transwell invasion test under low magnification (×100); while (b) illustrates the results of the Transwell invasion test under high magnification (×200). Cells that moved across the Transwell membrane were colored in a blue-purple hue using crystal violet staining solution). (b) Statistical analysis of cell migration through the Transwell membrane in each group at low magnification. (c) Statistical analysis of cell migration through the Transwell in each group at high magnification. The numerical details can be seen in Figure 10b(c) and (d).

3.6 Lathyrol inhibited the protein expression of MMP2 and MMP9 in 786-O cells

As shown in Figure 7 that MMP2 was mainly expressed in the cytoplasm of 786-O cells, but its presence was also detected in the nucleus (Figure 7a), and MMP9 localized mainly to the cell membrane (Figure 7b). In general, 786-O cells in groups B and C showed a significant inhibitory trend in the protein expression of MMP2 and MMP9 compared to other groups (Figure 7a and b). At low magnification (Figure 7a(a) and d(a)), the levels of MMP2 and MMP9 expression in both B and C groups were notably reduced compared to A group. At high magnification (Figure 7a(b) and d(b)), the levels of MMP2 and MMP9 in the A group were notably elevated compared to the B and C groups (P < 0.05). Due to that, lathyrol and nilutamide exhibit a marked inhibitory effect on the invasive capacity of 786-O cells.

Figure 7 Results of ICC staining for MMP2 expression in (a), and the combined results of ICC and DAB staining for MMP9 expression in (d). The appearance of brown granules in these sections serves as an indicator of positive expression. (a) Displays low-magnification images (×100) for closer inspection, while (b) offers high-magnification images (×400) for a more detailed view. (b) Statistical analysis of AODs pertaining to MMP2 expression at low magnification and (c) analogous analysis for MMP2 expression at high magnification. (e) Statistical analysis of AODs for MMP9 expression under low magnification and (f) corresponding analysis for MMP9 expression at high magnification. The precise numerical details can be found in Figure 10b(e)–(h).
Figure 7

Results of ICC staining for MMP2 expression in (a), and the combined results of ICC and DAB staining for MMP9 expression in (d). The appearance of brown granules in these sections serves as an indicator of positive expression. (a) Displays low-magnification images (×100) for closer inspection, while (b) offers high-magnification images (×400) for a more detailed view. (b) Statistical analysis of AODs pertaining to MMP2 expression at low magnification and (c) analogous analysis for MMP2 expression at high magnification. (e) Statistical analysis of AODs for MMP9 expression under low magnification and (f) corresponding analysis for MMP9 expression at high magnification. The precise numerical details can be found in Figure 10b(e)–(h).

3.7 Lathyrol promoted the expression of the AR, p-AR, and PSA proteins and inhibited the expression of the p-Akt protein in 786-O cells

After drug administration, in comparison to the A group’s 786-O cells, the B and C groups manifested an upregulation of AR and p-AR protein expression, accompanied by a downregulation of p-AR expression (Figure 8a). The 786-O cells within both B and C groups show markedly increased levels of AR and p-AR, accompanied by a notably diminished level of p-Akt, in comparison to the 786-O cells in A group. Nonetheless, there was no notable variation in the p-AR/AR ratio observed across the three groups (P > 0.05). Moreover, ICC results (Figure 9a) displayed that PSA was expressed mainly in the nucleus and the results of PSA expression did not exhibit any statistically significant difference (P > 0.05) among the three groups, as observed under both low and high magnification conditions (Figure 9a(a) and (b)).

Figure 8 (a) Western blot outcomes for the protein expression levels of p-AR, AR, p-Akt, and GAPDH; (b) statistical evaluation of AR expression; (c) statistical evaluation of p-Akt expression; (d) statistical evaluation of p-AR expression; and (e) statistical evaluation of the p-AR/AR ratio. The numerical details can be seen in Figure 10c(a)–(d).
Figure 8

(a) Western blot outcomes for the protein expression levels of p-AR, AR, p-Akt, and GAPDH; (b) statistical evaluation of AR expression; (c) statistical evaluation of p-Akt expression; (d) statistical evaluation of p-AR expression; and (e) statistical evaluation of the p-AR/AR ratio. The numerical details can be seen in Figure 10c(a)–(d).

Figure 9 ICC staining and DAB color development results for PSA expression are displayed in (a), with brown granules indicating positive expression. ((a) includes low-magnification (×100) images, while (b) includes high-magnification (×400) images). The statistical analysis of the AOD data for PSA expression under low magnification is shown in (b), and under high magnification in (c). The numerical details can be seen in Figure 10c(e) and (f).
Figure 9

ICC staining and DAB color development results for PSA expression are displayed in (a), with brown granules indicating positive expression. ((a) includes low-magnification (×100) images, while (b) includes high-magnification (×400) images). The statistical analysis of the AOD data for PSA expression under low magnification is shown in (b), and under high magnification in (c). The numerical details can be seen in Figure 10c(e) and (f).

Figure 10 Summary of numerical results. This figure is a summary and visualization of the numerical results from Figures 2–9. The specific experimental results can be found in the corresponding experimental results’ panel.
Figure 10

Summary of numerical results. This figure is a summary and visualization of the numerical results from Figures 2–9. The specific experimental results can be found in the corresponding experimental results’ panel.

4 Discussion

Initial signs of RCC in patients are not typical. However, those in advanced stages may have symptoms such as painless blood in urine, lower back pain, a mass in the abdomen, and other signs. The initial signs of RCC may not be readily apparent, and approximately 30–40% of individuals diagnosed with RCC already exhibit metastasis. Nevertheless, around 30% of individuals with RCC who receive surgery will encounter a relapse, potentially leading to the development of metastatic RCC (mRCC) [22]. Patients with mRCC have a grim prognosis, as their 5-year survival rate is below 10% and their average survival is less than 1 year [3,11,23]. Radical nephrectomy continues to be the primary treatment for RCC in clinical practice [24,25]. Patients who receive early surgical intervention have a more favorable prognosis than patients who do not. However, advanced RCC does not respond well to radiotherapy or chemotherapy [9]. Surgical treatment can only alleviate symptoms and reduce the tumor size, limiting RCC patients to opting for palliative care [26–28]. Therefore, effective treatment options for RCC urgently need to be developed.

The traditional Chinese herbal medicine system in China has high economic benefits and has demonstrated notable clinical effectiveness against tumors, with reduced side effects and toxicity [29,30]. As a TCM belonging to the genus Euphorbia, Leptochloa chinensis, which is warm in nature and pungent in taste has low toxicity, regulates the large intestine, liver and kidney, removes water, reduces swelling and blood stasis to eliminate symptoms, and exerts therapeutic effects on diseases such as phlegm retention, stagnation of swelling and edema. In recent years, studies of the antitumor activity of L. chinensis have led to further developments in the study of natural medicines for the treatment of tumors. Lathyrol is the dry mature seed of Euphorbia lathyris L., a TCM that are effective against tumors and can directly eliminate cancer cells, suppress the growth of tumor tissue, control the tumor microenvironment (TME), and reduce tumor cell resistance to drugs, ultimately enhancing the effectiveness of cancer treatments [31–33].

According to recent research, the activation and expression of AR can stimulate the growth and advancement of tumors at later stages. Moreover, the activation and expression of AR can promote the invasion, dissemination, growth, and advancement of cancer cells through different pathways, such as inhibiting the release of immune factors, boosting tumor immune escape, stimulating angiogenesis, and triggering the EMT process. AR also being utilized in the treatment of RCC, is involved in malignant biological behaviors, such as drug resistance [34–40], and is a well-known immune target. PSA is essential for the advancement of PCa cells as it serves as a target gene of AR and plays a significant role in the AR signaling pathway [41]. PSA levels rise as PCa advances, but inhibiting PSA can slow the proliferation and metastasis of cancer cells [42]. Phosphorylated serine/threonine protein kinase (p-Akt) is a key molecule in the AR signaling pathway and an important molecular target of AR signaling that combines with other pathways to exert its effects. Inhibiting the proliferation and migration ability of cancer cells and enhancing the effectiveness of clinical anticancer medications can be achieved by reducing the p-Akt/Akt ratio [43,44].

In pilot experiments, we investigated the anticancer effects of lathyrol and nilutamide by determining the most effective concentrations and revealed the anticancer mechanism of lathyrol and nilutamide against RCC cells. According to the ICC data, lathyrol and nilutamide enhanced the expression of AR and p-AR while suppressing the expression of p-Akt in 786-O cells. However, the impact of these antagonists on PSA expression was minimal, and to date, the association between lathyrol and AR has not been studied in China or abroad; furthermore, the impacts of AR antagonists on AR remain unclear. Through a literature review and preliminary experiments, we found that human RCC 786-O cells are negative for AR [45,46]. However, the application of AR antagonists may promote the expression of AR in cancer cells. Olson et al. [47] reported that the use of androgen deprivation therapy could enhance the levels of AR in human and mouse PCa cells, both in vitro and in vivo. Serçinoğlu et al. [48] reported that anti-AR therapy may increase the number of point mutations in AR or affect AR expression. Hence, considering the outcomes of these experiments, we speculate that lathyrol and nilutamide may not exert their anticancer effects through impacting the production of AR. Instead, these compounds likely competitively hinder AR expression, obstruct AR signal transmission, suppress the growth, movement and infiltration of 786-O cells, and stimulate cell apoptosis. Consequently, these effects could lead to an increase in AR variants or feedback stimulation of AR synthesis. It is also possible that while lathyrol and nilutamide exert their anticancer effects, they may promote the transcription and expression of certain factors and further promote AR expression and phosphorylation. Due to that, we believe that nilutamide still has some significance in this study based on its mechanism. As an AR blocker, nilutamide can compete with AR to inhibit its binding to androgen and suppress AR signal transduction, thereby exerting anticancer effects. Because of that the expression of AR in 786-O cells is increased after nilutamide therapy, but the expression of its downstream effector protein PSA is not affected, while the expression of p-Akt is lowered, and the malignant behavior of RCC cells is inhibited. Therefore, we hypothesize that nilutamide inhibits the binding of androgen to AR and inhibits AR signal transduction, thereby inhibiting the proliferation and invasive ability of RCC 786-O cells. Regarding the proliferative characteristics of 786-O cells, both lathyrol and nilutamide effectively suppressed cell proliferation, and lathyrol also suppressed the expression of the proliferation marker protein Ki67. However, nilutamide had a minimal impact on Ki67 protein expression, suggesting that this compound may regulate the proliferation of 786-O cells through alternative mechanisms. Regarding the apoptotic phenotype, the quantity of 3′-OH DNA fragments in 786-O cells was notably higher in both the negative control and experimental groups than in the DMSO group. The severity of the DNA breaks in these two groups was more pronounced than that in the other two groups, indicating that lathyrol and nilutamide could effectively trigger 786-O cell apoptosis. The decrease in the Bcl-2/Bax ratio induced by lathyrol and nilutamide enhanced the expression of cleaved-caspase3 and cleaved-caspase9. The protein expression of caspase3 and caspase9 was minimally affected by lathyrol and nilutamide, whereas the Bcl-2/Bax ratio was reduced. Increased caspase3, caspace9, cleaved-caspase3, and cleaved-caspace9 expression often indicates the occurrence of cell apoptosis [49–51]. Thus, we hypothesized that lathyrol and nilutamide enhance the activity of caspase family members by stimulating the upregulation of caspase3 and inducing the splicing of caspase9. Chen et al. [31] found that lathyrol inhibited the proliferation of A549 and H460 lung cancer cells and promoted the apoptosis of A549 and H460 lung cancer cells. This research provide evidence for our hypothesis. The outcomes from the scratch test demonstrated that the degree of migration of 786-O cells in both the negative control and experimental groups was significantly less than that observed in the model group. Both lathyrol and nilutamide exhibited a substantial inhibitory effect on the motility of 786-O cells, with nilutamide’s effect being notably more pronounced compared to that of lathyrol. Furthermore, Transwell assays, along with the evaluation of MMP expression, serve as crucial techniques for determining the invasive capabilities of cells. MMPs enhance the infiltration and invasion of tumors in the TME by breaking down the extracellular matrix, ultimately facilitating the migration and invasion of tumor cells [52–55]. Following the administration of lathyrol and nilutamide, the number of cells that traversed the Matrigel in both the negative control and experimental groups was significantly lower than that found in the model group. The suppressive impact of nilutamide on 786-O cells was evident. ICC results data show that MMP2 and MMP9 expression levels were reduced in 786-O cells in both the negative control and experimental groups than in the model group, indicating that the inhibitory effect of lathyrol was more pronounced. Hence, the invasion of 786-O cells can be strongly suppressed by lathyrol and nilutamide, consistent with the findings reported by Yan et al. [32]. These authors employed lathyrol to hinder the movement and infiltration of A549 and H1299 cells, which are associated with non-small cell lung cancer. During this process, the AR function of the cells is inhibited, leading to an obvious increase in the expression of AR and p-AR in B and C group cells to be responsive to the anticancer effects of nilutamide and lathyrol. This may be the probable cause of the phenomenon that the proliferation and invasion ability of RCC 786-O cells are inhibited, apoptosis is significantly induced, and AR expression is abnormally elevated.

The functioning of L. chinensis, an ancient Chinese remedy, on 786-O human RCC cells and Renca cells was examined in this study. Recently, studies have demonstrated that L. chinensis can impact cancer tissues by blocking the NF-κB pathway and related protein expression, inducing apoptosis in RCC cells, and suppressing TGF-β/Smad pathway protein expression and activation. According to recent research, the proliferation and invasion of RCC can be partially hindered by L. chinensis, and this effect is achieved by suppressing the production of invasion-related proteins in RCC xenografts and impeding the progression of EMT through the inhibition of crucial proteins such as AR and SPHK-2 [56–58]. Consequently, lathyrol plays a role in restraining the proliferation and invasion of RCC cells to some extent. Overall, we hypothesize that lathyrol can impact the AR expression and important proteins in the AR signaling pathways, thereby inhibiting some biological functions of 786-O human RCC cells, including significantly inhibiting their proliferation, migration, and invasion. However, the lack of studies on the precise gene-level identification and examination of alternative potential targets of lathyrol has hindered any further exploration of the AR pathway and its associated molecular mechanisms. Therefore, additional research is required to clarify the process and specific objectives associated with the progression of RCC, providing new insights for the clinical detection and management of RCC.

Finally, although this experimental study is limited by funding and other issues it still has many shortcomings, we believe that this study is still of certain importance. First of all, the current clinical treatment is still using radical nephrectomy as the main treatment for patients with RCC, and RCC is not sensitive to radiotherapy and chemotherapy. By studying the mechanism of action of lathyrol on RCC, we can provide additional anti-tumor means for patients with RCC who cannot undergo surgical treatment due to age, physical reasons, and economic conditions. Second, as one of the TCM system member, lathyrol has the advantages of high economic efficiency, significant clinical efficacy, and less side effects and toxicity in anti-tumor efficacy, which can provide effective anti-tumor therapy for patients who cannot perform surgical treatment, and plays a key role in the process of anti-tumor diagnosis and treatment. In addition, exploring the immunotargeted anti-tumor mechanism of TCM lathyrol by modern means adds an additional theoretical basis for the study of the mechanism of lathyrol inhibiting tumor growth, and provides novel ideas for the RCC diagnosis and treatment.

5 Conclusion

In summary, lathyrol has significant anticancer effects in vitro and may inhibit malignant behaviors, such as proliferation, migration, and invasion, in 786-O cells by affecting the expression of AR, inhibiting AR signal transduction, and inducing apoptosis.

tel: +86-371-60908781; fax: +86-371-60908800

  1. Funding information: This research was financially supported by Henan Province Chinese Medicine Scientific Research Special Project (2023ZY2090).

  2. Author contributions: Shengyou Song: conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing – original draft, visualization, project administration; Lunwei Tai: data curation, investigation; Lei Zhou: visualization, investigation; Junling Jiang: investigation, validation; Junfeng Zhao: conceptualization, writing – reviewing and editing, supervision, funding acquisition.

  3. Conflict of interest: All authors declare that there is no conflict of interests.

  4. Data availability statement: The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request. Source data are provided with this paper.

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Received: 2024-08-28
Revised: 2024-12-17
Accepted: 2024-12-17
Published Online: 2025-02-04

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2024-1136
Keywords for this article
lathyrol; renal cell cancer; androgen receptor; malignant behavior of tumor cells
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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