Background: Cancer remains a major global health challenge, with treatment efficacy often limited by drug resistance and adverse effects. Drug repurposing offers promising opportunities for developing novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, administered individually and in combination, in human cancer cell lines, as well as their potential interaction mechanisms. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05–50 mM) and caffeine (0.5–5 mM), either alone or in combination, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using a one-way ANOVA followed by Tukey’s post hoc test. Results: Metformin induced dose- and time-dependent cytotoxicity in all tested cell lines, with the lowest IC₅₀ values observed in HeLa and A549 cells after 48 h (2.28 and 3.30 mM, respectively; p < 0.05). Caffeine showed moderate antiproliferative activity, with the strongest effects observed at 2.03 mM in HeLa cells and 2.01 mM in HT29 cells (p < 0.05). The combined treatment produced effects that varied depending on both the cell line and exposure time. At earlier time points, transient synergistic effects were observed in certain cell lines, particularly HeLa cells; however, these effects were not sustained over time. With prolonged exposure, the interaction shifted predominantly toward antagonistic effects, indicating the reduced overall efficacy of the combination compared with the expected additive outcomes. Increased apoptosis and elevated p53 expression further supported the activation of tumor-suppressive pathways. Conclusions: Metformin exhibited significant anticancer activity in vitro, supporting its potential repurposing in oncology. However, the addition of caffeine did not uniformly enhance its efficacy and appeared to exert context-dependent effects. Further in vivo studies are required to confirm the clinical relevance of these findings.

Background:Cancer remains a major global health challenge, with treatment efficacy li-mited by drug resistance and adverse effects. Drug repurposing offers opportunities for novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, alone and in combination, in human cancer cell lines, and their potentialinteraction mechanisms. Methods:Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05–50 mM) and caffeine (0.5–5 mM), alone or combined, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test. Results:Metformin induced dose- and time-dependent cytotoxicity in all tested cell lines, with the lowest IC₅₀ values observed in HeLa and A549 cells after 48 h (2.28 and 3.30 mM, respectively; p < 0.05). Caffeine showed moderate antiproliferative activity, with the strongest effects at 2.03 mM in HeLa and 2.01 mM in HT29 cells (p < 0.05). The combined treatment produced effects that varied depending on both the cell line and exposure time. At earlier time points, transient synergistic effects were observed in certain cell lines, particularly HeLa; however, these effects were not sustained over time. With prolonged exposure, the interaction shifted toward predominantly antagonistic effects, indicating a reduced overall efficacy of the combination compared to expected additive outcomes.Increased apoptosis and elevated p53 expression further support the activation of tumor-suppressive pathways. Conclusions:Metformin exhibits significant anticancer activity in vitro, supporting met-formin repurposing in oncology. However,the addition of caffeine does not uniformly enhance its efficacy and appears to exert context-dependent effects.Further in vivo studies are required to confirm its clinical relevance. Keywords:AMPK;Antitumor activity; Apoptosis; Caffeine; Cancer cell lines;Chou–Talalay method; Drug repurposing;Docking;Metfomin;Molecular docking; p53;

Cancer cell metabolism represents a critical therapeutic target, particularly under conditions of metabolic stress induced by glycolysis inhibition. Nitroglycerin (glyceryl trinitrate, GTN), a nitric oxide donor, and 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, have individually demonstrated anticancer potential through modulation of cellular metabolism and redox balance. In this study, we investigated the cytotoxic and combined effects of GTN and caffeine under 2-DG-induced metabolic stress in human cancer cell lines (HeLa, A549, HT29, and MRC-5). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h treatments, while drug interactions were evaluated using the Chou–Talalay method and combination index (CI) values. 2-DG alone reduced cell viability in a concentration- and time-dependent manner, with IC₅₀ values ranging from 2.01 to 7.05 mM depending on the cell line and exposure period. The combined treatment further enhanced cytotoxicity, particularly in A549 cells, where viability decreased to approximately 63% after 48 h and the calculated IC₅₀ value for GTN in the presence of caffeine reached 0.143 μM. CI analysis demonstrated synergistic interactions in HeLa and A549 cells (CI < 1), whereas HT29 cells predominantly exhibited antagonistic responses (CI > 1). However, strong synergistic effects were also observed in MRC-5 fibroblasts, indicating limited selectivity toward cancer cells. Molecular docking suggested favorable in silico binding of GTN to aldehyde dehydrogenase 2 (ALDH2) and caffeine to the adenosine A2A receptor. Nevertheless, these findings should be considered exploratory and hypothesis-generating because target expression, enzymatic activity, and pathway activation were not experimentally validated. Overall, the results suggest that GTN enhances caffeine-induced cytotoxicity under metabolically stressed conditions through combined metabolic and redox perturbation, although the magnitude of the response depends on cellular context and warrants further mechanistic investigation.

Introduction/Objective. The objective of the study was to determine whether the local application of tranexamic acid (TXA) by pouring over the surgical wound reduces the incidence of postoperative hematoma and the occurrence of postoperative bleeding in the wound following inguinal hernia repair using the Lichtenstein technique. Methods. We conducted a prospective, randomized, double-blind clinical study in the period from June 2024 to February 2025. One hundred and twenty patients were divided into two groups, one group of patients who received TXA during surgery, and the other group where a placebo was administered. Subsequently, the groups were compared and analyzed by sex and age structure, the frequency of postoperative hematoma, and the pre- and postoperative levels of erythrocytes, hemoglobin, and platelets were recorded. Results. The results indicate that in the group where TXA was administered, postoperative hematoma occurred statistically significantly less often than in the group with a placebo (p < 0.05). The frequency of postoperative hematoma in the group of patients who were treated with TXA was 3.8%, while the frequency in the group of patients who were treated with a placebo was 13%. There was a statistically significant difference in the levels of platelets before and after surgery in the compared groups. Conclusion. We found that the topical application of TXA reduces the occurrence of postoperative hematoma, and thus the occurrence of postoperative bleeding, as well as reduces the postoperative drop in platelets.

Background: Cancer remains a major global health challenge, with treatment efficacy limited by drug resistance and adverse effects. Drug repurposing offers opportunities for novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, alone and in combination, in human cancer cell lines, and their potentialinteraction mechanisms. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05–50 mM) and caffeine (0.5–5 mM), alone or combined, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test. Results: Metformin induced dose- and time-dependent cytotoxicity in all cell lines, with the lowest IC₅₀ values in HeLa and A549 cells after 48 h (2.28 and 3.30 mM; p < 0.05). Caffeine showed moderate antiproliferative activity, with strongest effects at 2.03 mM in HeLa and 2.01 mM in HT29 cells (p < 0.05). Combined treatment demonstrated variable effects depending on the cell line and treatment duration, with limited synergistic interaction observed only under specific conditions, while predominantly antagonistic effects were detected overall. Increased apoptosis and elevated p53 expression suggest activation of tumor-suppressive pathways. Conclusions: Metformin exhibits significant anticancer activity in vitro, supporting metformin repurposing in oncology. However,the addition of caffeine does not uniformly enhance its efficacy and appears to exert context-dependent effects.Further in vivo studies are required to confirm its clinical relevance.

Background/Objectives: Lumbar radiculopathy can be managed non-surgically or surgically; however, comparative changes in quality of life and functional status between these treatment pathways remain clinically relevant. Therefore, this study aimed to compare six-month outcomes in patients treated non-surgically and those treated with lumbar microdiscectomy followed by rehabilitation. Methods: A prospective, non-randomized comparative cohort study included 100 patients with discogenic lumbar radiculopathy: 50 treated non-surgically and 50 treated by lumbar microdiscectomy. Both groups underwent medical rehabilitation and were assessed at admission, three months, and six months using the Short Form-36 Health Survey (SF-36), including the Physical Component Summary (PCS) and Mental Component Summary (MCS), and the Oswestry Disability Index (ODI). Results: PCS improved from 35.5 to 50.8 in the non-surgical group and from 28.8 to 49.2 in the surgical group. PCS was significantly higher in non-surgically treated patients at admission (p < 0.001) and three months (p < 0.05), whereas the difference was not significant at six months (p = 0.064). No between-group differences were found for MCS at admission, three months, or six months (p = 0.104, p = 0.871, and p = 0.323, respectively). ODI decreased from 51.5% to 22.5% in the non-surgical group and from 56.1% to 23.7% in the surgical group, without significant between-group differences at any assessment (p = 0.109, p = 0.162, and p = 0.427). Conclusions: Both treatment pathways were associated with substantial improvement. The initial between-group difference in physical quality of life diminished during follow-up, while mental quality of life and disability outcomes were similar between groups.