Endometrial cancer is the most common gynaecological malignancy in developed countries, and its increasing incidence is strongly associated with obesity. In most cases, the disease is driven by prolonged oestrogen exposure without adequate progesterone — a hormonal imbalance that is often linked to excess adipose tissue. Obesity contributes to more than half of all cases and is considered the leading modifiable risk factor. Dietary patterns can affect the risk of developing endometrial cancer not only through their impact on body weight, but also by modulating hormone levels, insulin resistance, and chronic inflammation. Lifestyle interventions that promote healthy nutrition and regular physical activity, and that prevent obesity, diabetes, and metabolic disorders, are essential components of prevention strategies. An appropriate diet may also improve prognosis, alleviate symptoms and reduce adverse effects of treatment. Future research should focus on tailored dietary approaches for specific histological and molecular subtypes, as well as high-risk populations. Current evidence suggests that a healthy diet is particularly important for women with obesity as part of endometrial cancer prevention.
Disulfiram, originally developed for the treatment of alcohol dependence, has recently gained attention for its potential applications in oncology and infectious diseases. In breast and pancreatic cancers, disulfiram forms copper complexes that inhibit tumor growth, induce oxidative stress, and enhance the efficacy of chemotherapy and radiotherapy. It targets cancer stem cells and modulates key enzymes such as aldehyde dehydrogenase (ALDH) and O6-methylguanine-DNA methyltransferase (MGMT), thereby increasing tumor sensitivity to agents such as gemcitabine and temozolomide. In glioblastoma, disulfiram also inhibits polo-like kinase 1 and proteasome activity, promoting apoptosis. In HIV therapy, disulfiram contributes to the “shock-and-kill” strategy by reactivating latent viral reservoirs without significant immune activation. In COVID-19, it may inhibit viral proteases (Mpro, PLpro) and reduce neutrophil extracellular trap (NET) formation, potentially mitigating disease severity. Observational studies suggest a reduced risk of infection and symptom development among disulfiram users. Beyond these areas, disulfiram has demonstrated in vitro activity against a broad spectrum of pathogens, including Borrelia burgdorferi, vancomycin-resistant bacteria, hepatitis C virus, and various parasites. It has also been explored as an adjunct in the treatment of cocaine dependence. Although most findings remain preclinical, the breadth of disulfiram’s biological activity supports continued investigation into its therapeutic potential across diverse medical domains.
Mesalamine, a Biopharmaceutics Classification System (BCS) Class IV drug, exhibits poor solubility and low permeability, posing considerable challenges for accurate quantification. The aim of this study was to develop and validate a robust, cost-effective, and environmentally sustainable UV-visible spectrophotometric method for the precise quantification of mesalamine in ethanol and phosphate-buffered saline (PBS, pH 7.4), in accordance with International Council for Harmonisation (ICH) Q2(R1) guidelines. The method was optimized at a maximum absorption wavelength of 300 nm and validated with respect to linearity, accuracy, precision, specificity, and sensitivity through the determination of the limits of detection (LOD) and quantification (LOQ). Calibration curves were constructed over a concentration range of 10–100 µg/mL. The proposed method demonstrated excellent linearity, with a correlation coefficient (R²) of 0.99. Relative standard deviation (%RSD) values remained below 0.5%, indicating good repeatability and reproducibility. Accuracy was confirmed by recovery values ranging from 99.3% to 101.9%. The calculated LOD and LOQ values for mesalamine in ethanol (10.0 and 21.1 µg/mL, respectively) and PBS (6.8 and 20.6 µg/mL, respectively) were within acceptable limits according to ICH recommendations, confirming the sensitivity and reliability of the analytical method. The validated UV-visible spectrophotometric method provides a rapid, reliable, and cost-effective approach for the routine quantification of mesalamine during formulation development and pharmaceutical quality control. Owing to its simplicity and resource-efficient nature, the method represents a practical alternative to more complex chromatographic techniques. Further studies may broaden its applicability through integration with advanced analytical approaches in pharmaceutical sciences.
Patients receiving antithrombotic therapy are at increased risk of bleeding. In some cases, bleeding may be the first manifestation of an underlying malignancy. We investigated newly diagnosed cancers associated with gastrointestinal or genitourinary bleeding among patients enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial and assessed the risk of recent cancer diagnoses following bleeding at these sites. During a 23-month follow-up of 27,395 patients (mean age: 68 years; 21% female), 2,678 patients (9.8%) experienced any bleeding, 713 (2.6%) experienced major bleeding, and 1,084 (4.0%) were diagnosed with cancer. Among the 2,678 patients with bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was 20-fold more common in patients with newly diagnosed gastrointestinal cancers (7.4% vs. 0.5%; HR 20.6, 95% CI: 15.2-27.8) and 1.7-fold more common in those with non-gastrointestinal cancers (3.8% vs. 3.1%; HR 1.70, 95% CI: 1.20-2.40). Genitourinary bleeding was associated with a 32-fold increased risk of newly diagnosed genitourinary malignancy (15.8% vs. 0.8%; HR 32.5, 95% CI: 24.7-42.9), while urinary bleeding was linked to a 98-fold higher risk of newly diagnosed urinary cancer (14.2% vs. 0.2%; HR 98.5, 95% CI: 68.0-142.7). Non-gastrointestinal, non-genitourinary bleeding was associated with a threefold higher risk of non-gastrointestinal, non-genitourinary cancers (4.4% vs. 1.9%; HR 3.02, 95% CI: 2.32-3.91). Among patients with atherosclerosis receiving antithrombotic therapy, gastrointestinal or genitourinary bleeding was associated with an increased incidence of cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt evaluation for possible malignancy at these sites.
This study presents the formulation and evaluation of orally disintegrating tablets (ODTs) containing high concentrations of micronized lurasidone hydrochloride, an atypical antipsychotic agent. The research focuses on optimizing two key material attributes: particle size distribution (PSD) and specific surface area (SSA). These optimizations enhance granulation performance and tablet quality. Fluidized-bed granulation was employed alongside dry coating techniques and various glidants to improve powder flowability and reduce cohesion. Comprehensive characterization included pre- and post-compression parameters such as visual evaluation, sieve analysis, weight variation, hardness, tensile strength, friability, disintegration, and dissolution testing. The results demonstrated that API batches with D50 > 3.5 µm achieved 85% drug release within 15 minutes. No significant differences were observed between formulations containing different glidants, indicating flexibility in excipient selection. These results underscore the importance of controlling PSD and SSA and employing effective dry coating and fluidization strategies to produce robust and reproducible ODTs. The developed tablets improve patient compliance and therapeutic efficacy for psychotic disorders and provide valuable insights for the future development of patient-friendly dosage forms.
In this study, a combined therapeutic strategy integrating photobiomodulation (PBM) with an antibacterial hydrogel containing silver nanoparticles and europium-activated lanthanum orthovanadate nanoparticles (Ag/LaVO₄3+ NPs) was developed to enhance wound healing. This integrated approach was designed to provide complementary effects by simultaneously improving antibacterial activity and promoting tissue regeneration. The study aimed to investigate the roles of vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and keratinocyte autocrine factor (KAF) in reparative processes occurring in chronic wounds following treatment with Ag/LaVO₄3+ NPs hydrogel and PBM therapy. Thirty WAG rats were randomly assigned to five groups: Con, Gel (Ag/LaVO₄3+ NPs hydrogel), PBM (660 nm, 50 mW, 1 J/cm²), Gel+PBM, and intact. Chronic wounds were induced, and serum levels of VCAM-1, ET-1, and KAF were determined using enzyme-linked immunosorbent assay (ELISA). In addition, histological analysis was performed. Experimental wounds were associated with elevated serum levels of VCAM-1 and ET-1 in the control animals, which is consistent with endothelial activation under inflammatory conditions. PBM therapy reduced the levels of these markers, whereas the combined Gel+PBM treatment produced the most pronounced effect, suggesting a greater attenuation of endothelial activation and the establishment of conditions favorable for wound healing. Serum KAF levels exhibited only a transient increase on day 3 in the control group and remained unchanged in the treated groups. The combination of PBM therapy and Ag/LaVO₄3+ NPs hydrogel was associated with reduced ET-1 and VCAM-1 levels, consistent with attenuated endothelial activation during wound healing. These changes were accompanied by improved re-epithelialization; however, the underlying mechanisms require further investigation.
This study aimed to evaluate the spectrum of bacterial pathogens responsible for chronic bacterial prostatitis among patients from Babylon Province and Al-Mahawel District, Iraq, and to assess their antimicrobial resistance patterns as well as the prevalence of selected virulence genes. A total of 150 bacterial isolates were recovered from urine cultures, expressed prostatic secretions, and post-massage urine samples. Patients were categorized into three age groups, with individuals aged 40–60 years representing the largest group (83 patients). The results showed that Staphylococcus aureus was the predominant Gram-positive pathogen, accounting for 73 of 150 isolates (48.66%), followed by Streptococcus pyogenes with 5 isolates (3.33%). Among Gram-negative bacteria, Escherichia coli was the most frequently isolated species, accounting for 48 isolates (32%), followed by Pseudomonas aeruginosa (9 isolates; 6%), Klebsiella pneumoniae (5 isolates; 3.33%), Proteus mirabilis (4 isolates; 2.66%), and Enterobacter aerogenes (2 isolates; 2%). Antimicrobial susceptibility testing revealed that S. aureus exhibited the highest resistance to cefotaxime (97.27%), followed by ceftriaxone (95.9%) and penicillin (93.16%). In contrast, gentamicin showed the greatest antibacterial activity, with a susceptibility rate of 94.52%, followed by imipenem (93.15%) and vancomycin (91.78%). Molecular analysis of biofilm-associated genes demonstrated that 76% of S. aureus isolates carried the icaA gene, whereas the icaD gene was detected in 66% of the isolates. These findings highlight the high prevalence of multidrug-resistant pathogens in chronic bacterial prostatitis and emphasize the importance of molecular characterization in guiding effective therapeutic strategies.
Sodium valproate (SV) is a widely used antiepileptic drug; however, its therapeutic application may be limited by its potential to induce oxidative stress. The present study evaluated the protective effect of resveratrol (REV) on CREB gene expression and malondialdehyde (MDA) levels in mouse neural tissue following prenatal exposure to sodium valproate. Fifteen Balb-C mice were kept in five groups of three per cage (two females and one male) and monitored daily for estrous cycles. After confirming pregnancy, the mice were divided into the following five groups: control, SV (400 mg/kg), SV (400 mg/kg) + REV (600 mg/kg), SV (400 mg/kg) + REV (350 mg/kg), and SV (400 mg/kg) + REV (225 mg/kg). Drug interventions began on days eight to eighteen of pregnancy and continued until delivery. Two to three days before birth, eight fetuses from each group were surgically removed under anesthesia. Thebrain tissue was collected and CREB gene expression was measured using real-time PCR. Lipid peroxidation was assessed using the thiobarbituric acid reactive substances (TBARS) method to measure malondialdehyde (MDA) levels. Sodium valproate significantly reduced CREB gene expression in brain tissue (p < 0.001) and increased MDA levels (p < 0.001). In contrast, resveratrol significantly upregulated CREB expression (p < 0.001) and reduced MDA concentrations, with the most pronounced gene expression effect observed at 350 mg/kg and the strongest reduction in lipid peroxidation at 600 mg/kg. The findings showed that resveratrol can effectively counteract sodium valproate-induced CREB gene downregulation and oxidative stress.
The anthranilic acid derivative, anthranilic hydrazide, is a very important compound in medicine, although it was recently developed to reduce the side effects of anthranilic acid. Since anthranilic acid derivative hydrazide is a newly produced product, there are few methods for estimating this significant component. Consequently, a simple, inexpensive, and rapid spectrophotometric approach has been developed to determine this chemical in various samples. The two-step method consists of oxidizing the compound with potassium periodate in an acidic medium. A red compound gradually forms after coupling with the 2-amino-4-chloro phenol reagent. Then, the concentration of the compound steadily increases in the second step. The method followed Beer's law at concentrations ranging from 1 to 32.5 µg/mL with a Sandall's value of 0.0245 µg-2 cm-1 and a molar absorptivity of of 0.899×10⁴ L mol-1 cm-1. This method was successful in determining the amount of anthranilic acid derivative hydrazide in several samples.
Candida species have emerged as a global threat due to their rapid worldwide spread and multidrug-resistant properties. Therefore, novel and more effective antifungal agents, including natural-based preparations, are being actively sought. Essential oil (EO) components, including α-bisabolol, carvacrol, eugenol, linalool, menthol, and thymol, were evaluated in vitro for their antifungal, antioxidant, and anti-inflammatory activities. The aim of this study was to select EO compounds demonstrating the highest anticandidal activity together with promising antioxidant and anti-inflammatory properties for potential use as active ingredients in topical preparations. The activity of the tested EO compounds against five reference yeast strains belonging to Candida spp. was assessed in vitro using the broth microdilution method according to the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI). All EO compounds demonstrated potential anticandidal activity, with minimum inhibitory concentrations (MICs) ranging from 0.25 to 4 mg/mL, and exhibited fungicidal properties (MFC/MIC = 1–4). The highest activity was observed for α-bisabolol (MIC = 0.25–1 mg/mL), followed by carvacrol (MIC = 0.25–2 mg/mL), thymol (MIC = 0.5–2 mg/mL), and eugenol (MIC = 0.5–2 mg/mL). Eugenol exhibited the strongest antioxidant properties, even at a concentration of 0.1 mg/mL, as demonstrated by the DPPH assay. Moreover, this compound showed the highest anti-inflammatory activity, reflected by cyclooxygenase-2 (COX-2) inhibition of approximately 45% at a concentration of 0.5 mg/mL. Based on the obtained results, eugenol appears to be the most promising candidate for the development of topical preparations intended for the treatment of superficial infections caused by Candida spp.
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) plays a pivotal role in the development of chronic diseases, including type 2 diabetes mellitus (T2DM) and its related metabolic disturbances. This study aimed to assess the biomarker 8-iso-prostaglandin-F2a (8-iso-PGF2a) as an indicator of oxidative stress T2DM patients and to investigate its association with dyslipidemia, with the objective determining its potential value in predicting early diabetesrelated complications. The study included 90 participants: 60 T2DM patients (30 with dyslipidemia and 30 without) and 30 age and sexmatched healthy controls. Fasting serum samples were analyzed for glucose and lipid profile using an autoanalyzer, while C-reactive protein (CRP) and 8-iso-PGF2a levels were measured using ELISA. Compared with healthy controls, patients with T2DM exhibited markedly elevated levels of oxidative stress and inflammatory markers, including significant increases in both 8-iso-PGF2a and CRP. Among individuals with T2DM, those with dyslipidemia showed substantially higher 8-iso-PGF2a concentrations and a slightly higher CRP levels compared with patients without dyslipidemia. Diagnostic assessment indicated that 8-iso-PGF2a showed moderate ability to distinguish T2DM patients with dyslipidemia from those without. These findings suggest that elevated levels of 8-iso-PGF2a, particularly in dyslipidemic T2DM patients, may serve as a promising early biomarker for assessing the risk diabetes-related complications.
This study found a strong association between elevated levels of highly sensitive C-reactive protein (hs-CRP) and vital lipid markers in dyslipidemic pre-, peri-,and postmenopausal women, indicating the need to screen them early for atherosclerotic cardiovascular risk. These subjects were advised to make dietary and lifestyle changes to overcome dyslipidemia and prevent the development and progression of atherosclerotic cardiovascular disease (ASCVD) during menopause. No such studies have examined the relationship between hs-CRP and lipid markers, especially in dyslipidemic women. Surprisingly, significant associations were also observed between hs-CRP and triglycerides (TG), as well as between hs-CRP and LDL-cholesterol (LDL-C) in premenopausal women with dyslipidemia. These correlations suggest that hs-CRP and the studied lipid markers are better indicators of the possible onset of ASCVD in women at later ages.
Diabetic nephropathy, one of the most prevalent complications of diabetes mellitus, is driven by hyperglycemia-induced overproduction of reactive oxygen species (ROS) and pro-inflammatory cytokines, ultimately resulting in structural and functional renal impairment. This study evaluated the renoprotective effects of a flavonoid-rich extract derived from Ocimum gratissimum leaves in a streptozotocin (STZ)-induced diabetic rat model. Type 2 diabetes mellitus was induced by intraperitoneal administration of STZ (45 mg/kg body weight) following one week of 20% (w/v) fructose supplementation. Rats were randomly assigned to five groups (n = 8): negative control (NC), diabetic control (DC), diabetic rats treated with low-dose (150 mg/kg) and high dose (300 mg/kg) O. gratissimum flavonoid-rich extract (LDOGFL and HDOGFL, respectively), and metformintreated diabetic rats (200 mg/kg; MET). On day 22, blood and kidney tissue was collected for assessment of redox status, inflammatory biomarkers, kidney function indices (creatinine, urea, and uric acid), electrolyte concentrations, kidney-specific acid phosphatase (ACP) and alkaline phosphatase (ALP) activities, mRNA expression of KIM-1 and TGF-β1, and histopathological changes. Treatment with LDOGFL, HDOGFL, or MET significantly (p < 0.05) improved redox balance, reduced inflammatory cytokines, and lowered creatinine, urea, and uric acid levels compared with untreated diabetic controls. Electrolyte profiles and ACP/ALP activities increased significantly (p < 0.05), whereas mRNA expression of KIM-1 and TGF-β1 was markedly downregulated. Histopathological examination revealed enhanced epithelial cell integrity within renal convoluted tubules and glomeruli in treated groups. Collectively, these findings indicate that the flavonoid-rich extract of O. gratissimum leaves confers renoprotective benefits in diabetic nephropathy by attenuating oxidative stress, suppressing inflammation, and improving renal function.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and represents a major global health burden due to its high incidence, limited treatment options, and negative impact on patient quality of life. This study aimed to evaluate the anticancer potential of green‑synthesized zinc oxide nanoparticles (ZnO NPs) as a natural alternative therapeutic strategy against HCC. ZnO NPs were biosynthesized using Camellia sinensis leaf extract. The cytotoxic activity of ZnO NPs against human hepatocellular carcinoma cells (HepG2) was assessed using the MTT assay following 72 hours of treatment. Antioxidant activity was determined using the DPPH free radical scavenging assay. Hemocompatibility was evaluated using an erythrocyte hemolysis assay, while genotoxic effects were examined using a DNA fragmentation assay. ZnO NPs exhibited a significant, concentration‑dependent cytotoxic effect on HepG2 cells. Cell viability decreased to 42.13% at 0.5 μg/mL and 26.84% at 5 μg/mL after 72 hours of exposure. The IC50 value was calculated as 2.87 μg/mL, indicating strong antiproliferative activity at low concentrations. Antioxidant analysis revealed enhanced free radical scavenging activity with increasing ZnO NP concentrations, reaching a maximum of 81.63% at 1 μg/mL and a minimum of 63.73% at 0.12 μg/mL. Hemolysis levels remained below detectable limits at all tested concentrations (0.12-1 μg/mL), demonstrating excellent hemocompatibility. Moreover, ZnO NPs did not induce DNA fragmentation, confirming the preservation of DNA integrity. The findings of this study demonstrate that ZnO NPs possess significant anticancer activity at low concentrations while exhibiting excellent hemocompatibility and no detectable DNA damage in vitro.
The growing interest in developing coatings for pharmaceutical products that are free of titanium dioxide (TiO2) stems from concerns about potential health risks and resulting regulatory changes. Finding alternatives to TiO2 is essential to meeting the requirements of the new guidelines. For generic drugs, maintaining compliance with the dissolution profiles of the reference drug is also important. This study evaluated the impact of different TiO2-free coating formulations on the dissolution profiles and eligibility for a biological equivalence exemption of a BCS Class IV drug product in two strengths. Specifically, the study aimed to determine whether these coatings could replicate the dissolution profile of the reference product for the high-strength and meet the criteria for exemption from the bioequivalence requirement for the low strength. Tablet cores containing two BCS Class IV active ingredients were manufactured and coated with four different TiO2-free coatings in two strengths. We evaluated the tablets' physical parameters and dissolution profiles. Similarity of the dissolution profiles was statistically evaluated in relation to the reference medicinal product and between different strengths. Different TiO2-free coatings altered the dissolution profile of a BCS Class IV drug product depending on the testing environment. This variability suggests that some coatings may hinder dissolution, while others may facilitate it under certain conditions. These results underscore the importance of thoroughly testing different TiO2-free coatings during the development of BCS Class IV drugs. The choice of coating should be tailored to the specific drug formulation and its intended use.
Tenofovir disoproxil fumarate (TDF) is widely used in the treatment of HIV-infected adults and is also approved for the management of chronic hepatitis B in adults, where it is administered in combination with other antiretroviral agents. The present study employed Design-Expert (R) software to investigate the effects of Kolliphor (R) P188 (g), Methocel (R) K100 Premium LV (g), and polyethylene glycol (mL) concentrations on the drug release characteristics of a topical TDF gel formulation. Eight formulations, including three center points, were prepared and evaluated for physical appearance, spreadability, syringibility, washability, pH, and ex vivo drug release. The interactions between formulation variables and drug release were also assessed. The results demonstrated statistically significant differences among formulations (p < 0.05). The findings indicate that polymer concentration is a critical formulation variable that must be carefully optimized to achieve a topical gel with desirable performance characteristics.
Oncology patients face numerous challenges resulting both from their underlying disease and from the adverse effects of anticancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is among the most serious complications associated with chemotherapy. The sensory and motor disturbances observed in the course of CIPN are often progressive and may be irreversible, while severe and chronic pain leads to a substantial reduction in patients' quality of life (QoL). This narrative review summarizes currently available topical treatment options for CIPN, focusing on substances that have shown potential clinical benefit. The pathogenesis of CIPN remains incompletely understood, and existing treatment strategies are frequently insufficient or associated with significant adverse effects. Consequently, both the prevention and management of CIPN remain important challenges in contemporary medicine. Recently, increasing attention has been directed toward topically administered agents, including formulations based on phenytoin, lidocaine, amitriptyline, capsaicin, cannabinoids, duloxetine, ketamine, and baclofen. These therapies may alleviate neuropathic symptoms and improve QoL without the systemic complications commonly associated with oral or intravenous pharmacotherapy. The use of topical medications may also allow for a reduction in systemic analgesic doses and is often favored due to their more favorable safety profile. Therefore, topical agents should be considered promising therapeutic options aimed at minimizing systemic side effects and optimizing the current pharmacological management of patients with CIPN.
Breast cancer is one of the leading causes of cancer-related mortality among women worldwide. The Wnt/3-catenin signaling pathway, particularly the WNT3A ligand, plays a pivotal role in mammary gland homeostasis and tumorigenesis. However, its expression profile in malignant and benign breast lesions remains unclear. This study aimed to evaluate the expression level of the WNT3A gene in ductal breast carcinoma compared with benign fibroadenoma tissues and to assess its potential diagnostic and prognostic value. Breast tissue samples were obtained from 31 women with ductal carcinoma and 14 women with fibroadenoma. WNT3A expression was analyzed using quantitative real-time polymerase chain reaction, with 3-actin as the endogenous control. Statistical analyses included the ACt method, the Mann-Whitney U test, Pearson correlation, logistic regression, and receiver operating characteristic (ROC) analysis. WNT3A expression was significantly lower in ductal carcinoma tissues than in fibro-adenoma samples (fold change = 0.32; p = 0.043). ROC analysis demonstrated moderate discriminatory power (AUC = 0.695; specificity = 0.87; sensitivity = 0.46). No significant correlations were observed between WNT3A expression and age, tumor size, lymph node involvement, or prognostic stage. Logistic regression revealed a non-significant trend toward increased cancer risk associated with decreased WNT3A expression (OR = 1.442; p = 0.153). Down-regulation of WNT3A may differentiate malignant from benign breast lesions and may reflect early dysregulation of the Wnt signaling pathway. Although not associated with clinical stage or TNM classification, WNT3A shows potential as a diagnostic biomarker and warrants further investigation.
Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent that may induce acute kidney injury (AKI), posing a major clinical challenge. This study investigated the renoprotective effects of Valsartan, Leucovorin and their combination in mitigating methotrexate (MTX)-induced renal damage in Wistar rats. The aim was to evaluate these effects in a rat model of MTX-induced acute kidney injury (AKI). After approval by the Institutional Animal Ethics Committee (IAEC), forty male Wistar rats were divided into five groups: control (saline), MTX (single intraperitoneal injection of 20 mg/kg), Valsartan (10 mg/kg/day), leucovorin (10 mg/kg/day), and combination (Valsartan plus leucovorin). Drug treatment was initiated one day before MTX administration and continued orally for five days. Renal function was assessed by measuring serum creatinine and blood urea nitrogen (BUN). Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were evaluated as inflammatory markers, while malondialdehyde (MDA) and glutathione (GSH) were assessed as oxidative stress markers. Histopathological examination of renal tissue was also performed. Data were analyzed using GraphPad Prism version 6. The MTX group showed significant renal dysfunction (p < 0.001) and increased inflammatory and oxidative stress markers. Both Valsartan and leucovorin produced partial renoprotective effects, with Valsartan significantly reducing oxidative stress (p < 0.001) and leucovorin markedly decreasing inflammatory markers (p < 0.001). The combination therapy demonstrated the most pronounced renoprotective effect (p < 0.001), as evidenced by improved renal function and reduced oxidative damage and inflammation. Histopathological analysis revealed decreased tubular necrosis and inflammatory infiltration in the combination group. Valsartan and leucovorin exerted individual renoprotective effects; however, their combined administration provided highly significant protection against MTX-induced AKI. These findings suggest that combination therapy may represent a promising strategy for preventing renal injury in patients undergoing MTX treatment.
Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterized by persistent inflammation, edema, and joint pain. Growth differentiation factor 15 (GDF-15) is a cytokine whose concentration increases in chronic inflammatory states. It has been recognized as both a pro-inflammatory mediator and a potential contributor to the development of cardiovascular disease due to its association with systemic inflammation and metabolic disorders. The aim of this study was to evaluate serum GDF-15 levels and atherogenic indices as predictors of disease activity in patients with RA. A total of 150 RA patients and 150 healthy controls were included. Serum concentrations of GDF-15, rheumatoid factor (RF), C-reactive protein (CRP), and anti-citrullinated protein antibodies (ACPA) were measured using ELISA. Lipid parameters, including total cholesterol, triglycerides (TG), and HDL-C, were assessed spectrophotometrically. Based on the DAS28-CRP calculator, RA patients were classified into high disease activity (HDA; DAS28-CRP > 5.1) and moderate disease activity (MDA) groups. Multivariate general linear model (GLM) analysis and Receiver Operating Characteristic (ROC) curve assessment were performed to identify predictors of RA activity. The results indicated that RA status explained 92.1% of the variance in the measured serum biomarkers. GDF-15 was identified as the most sensitive predictor of elevated disease activity, followed by the atherogenic indices CRI-I, AC, and AIP. Patients in the HDA group demonstrated significantly higher levels of GDF-15, CRP, ESR, and ACPA compared with those in the MDA group. GDF-15 exhibited a strong positive correlation with key inflammatory markers, including ESR and CRP. These findings suggest that GDF-15, CRI-I, AC, and AIP are the most sensitive predictors associated with increased RA activity. The combined use of GDF-15 and atherogenic indices yielded the largest area under the ROC curve, indicating their potential value in assessing RA severity. Moreover, RA patients showed elevated cholesterol levels and adverse atherogenic profiles, placing them at heightened risk for cardiovascular diseases linked to atherosclerosis.
