Introduction: Atopic dermatitis (AD) or eczema is a common inflammatory skin condition in Saudi Arabia, impacting adults with a varying prevalence. Previous research in the Aseer province has indicated that a significant proportion of dermatological patients resort to complementary and alternative medicine (CAM) to treat AD.

Objective: To investigate the nature, prevalence, and influence of CAM usage among Saudi adults with AD.

Methods: This cross-sectional study utilized an electronic survey distributed to Saudi adults through social media platforms and included adults diagnosed with AD for over a year.

Results: Our study included 163 participants with atopic dermatitis; 73.6% were females, 57.7% were aged 18-24, and 65.0% were from the Central region. Most participants were single (63.2%), students (47.2%), and had a monthly income < 5000 SAR (69.3%). CAM usage was prevalent (62%), with 36.8% reporting positive effects. Gauze moistened with warm water and olive oil was the most common remedy (16.4%). Motivations for CAM usage included dissatisfaction with medical drugs (55.8%). Logistic regression revealed significant factors for CAM usage, including the impact of AD on quality of life (regression coefficient/beta coefficient [B] = 0.618, p= 0.005, odds ratio/Exp[B] = 1.856) and the belief in CAM for treating skin diseases (B = 1.282, p= 0.001, Exp[B] = 3.604).

Conclusion: Our study on AD in Saudi participants revealed a prevalence of CAM usage, notably gauze moistened with warm water. Various factors, including the impact of AD on quality of life and belief in CAM for treating skin diseases, significantly influence CAM usage.

Introduction: The albumin combined with the neutrophil-to-lymphocyte ratio (NLR) score may be a useful marker of inflammation, but its associations with post-operative complications in colon cancer patients are unknown.

Objective: This study aims to construct and validate a predictive model incorporating albumin and NLR to predict post-operative complications in patients who underwent colon cancer resection.

Methods: A retrospective analysis was conducted on patients who underwent colon cancer resections between 2019 and 2021 at Sun Yat-sen Memorial Hospital. Clinical characteristics and systemic inflammatory markers, including lymphocytes and neutrophils, were collected. Post-operative complications served as the primary outcome. Logistic regression analyses were performed to identify the potential risk factors for post-operative complications after colon cancer resection. Nomograms with or without albumin and NLR score for post-operative complications were further constructed according to the results of the multivariable logistic regression analysis using the Akaike information criterion.

Results: Pre-operative albumin combined with NLR score (p=0.01; odds ratio [OR]: 2.69; 95% confidence interval [CI]: 1.90-8.06), age (p=0.007; OR: 1.05; 95% CI: 1.01-1.09), intraoperative blood transfusion (p=0.002; OR:5.32; 95% CI: 1.87-15.15), and duration of surgery (p=0.001; OR:1.70; 95% CI: 1.24-2.34) were identified as independent risk factors for post-operative complications. The nomogram, which included pre-operative albumin and NLR scores, demonstrated superior predictive performance, with a concordance index of 0.821 (95% CI: 0.758-0.883) and improved calibration.

Conclusion: Pre-operative albumin and NLR score are independent risk factors for post-operative complications following colon cancer resection. The developed nomogram incorporating these markers exhibited enhanced predictive capability for post-operative complications.

Introduction: Gastric cancer (GC) exhibits a poor prognosis with high metastasis rates. This study investigates Vitamin D receptor’s (VDRs) role in suppressing GC metastasis through autophagy.

Objective: To elucidate the molecular mechanism by which VDR suppresses GC invasion and metastasis through autophagy regulation.

Methods: VDR expression was assessed in 91 paired GC and adjacent normal tissues using immunohistochemistry. The effects of Vitamin D on GC cell proliferation, cell cycle, migration, and invasion were evaluated using Cell Counting Kit-8, flow cytometry, wound healing, and Transwell assays. The autophagic activity was examined through LysoTracker Red staining, monomeric red fluorescent protein-green fluorescent protein-LC3 fluorescence, and transmission electron microscopy. The roles of VDR, autophagy-related protein 13 (ATG13), and Beclin1 in autophagy regulation were investigated through gene knockdown and silencing. A nude mouse peritoneal metastasis model was used to validate the anti-metastatic effects of the Vitamin D/VDR pathway.

Results: VDR expression was significantly downregulated in GC tissues, correlating with lymph node metastasis and poor prognosis (p<0.001). Vitamin D treatment upregulated VDR, ATG13, and Beclin1 expression, enhancing autophagosome and autolysosome formation without altering cell proliferation or apoptosis, likely due to a cytostatic autophagic response. Silencing ATG13or BECN1abolished the inhibitory effects of Vitamin D/VDR signaling on cell migration and invasion. VDR knockdown promoted peritoneal metastasis, whereas Vitamin D treatment suppressed it.

Conclusion: This study provides novel evidence that Vitamin D/VDR signaling inhibits GC metastasis by influencing ATG13/Beclin1-mediated autophagy, offering potential therapeutic targets for GC management.

Introduction: Observational epidemiological studies investigating the association between cathepsins and psychiatric disorders have reported inconsistent results.

Objectives: The objective of this study was to evaluate the potential causal effects of cathepsins on psychiatric disorders using Mendelian randomization (MR) analysis.

Methods: A two-sample MR analysis was conducted using single-nucleotide polymorphisms as instrumental variables to examine the effects of cathepsins on psychiatric disorders. The study assessed both the individual and combined impacts of various cathepsins through univariable and multivariable MR analyses. Statistical techniques included the inverse-variance weighted method, along with supplementary approaches such as MR-egger regression, to ensure a comprehensive assessment.

Results: Univariable MR analysis demonstrated a significant correlation between cathepsin G and bipolar disorder, as well as between cathepsin S and depression. In addition, multivariate MR analysis further confirmed that elevated levels of cathepsin G were significantly linked to an increased risk of bipolar disorder, while elevated levels of cathepsin S were linked to a higher risk of depression - even after adjusting for the effects of other cathepsins. Reverse MR and sensitivity analyses supported the robustness of these findings.

Conclusion: This study suggests that cathepsin G and S are casually associated with an increased risk of bipolar disorder and depression, respectively. However, due to the limitations of the MR approach, including pleiotropic effects, these associations should be considered with caution.

Introduction: Cutaneous melanoma, a highly aggressive malignant tumor, continues to pose significant challenges in early diagnosis and prognosis assessment. Although anoikis-related genes (ARGs) play crucial roles in tumor progression, systematic molecular diagnostic biomarkers remain lacking.

Objective: This study aims to elucidate the molecular mechanisms and diagnostic value of ARGs in cutaneous melanoma using advanced bioinformatics and machine learning approaches.

Methods: Multiple melanoma datasets from The Cancer Genome Atlas and GEO databases (GSE3189, GSE15605, GSE19234, GSE65904, and GSE66839) were integrated to analyze ARG expression patterns. Differential expression analysis identified candidate genes significantly associated with cutaneous skin melanoma. A total of 113 machine learning models were employed to screen and validate candidate genes, with receiver operating characteristic curves evaluating diagnostic value. Core genes were identified through protein-protein interaction (PPI) networks. The immune infiltration correlations of core genes were analyzed, and their tissue-level expression was validated using immunohistochemistry.

Results: Twenty-two ARGs were significantly enriched in cancer signaling pathways, including phosphoinositide 3-kinase-protein kinase B, hypoxia-inducible factor 1, and programmed death-ligand 1. Nine candidate genes were identified through differential and intersection analysis, and eight model genes were further screened using machine learning. Seven genes exhibited high diagnostic efficacy in both training and external validation sets (area under the curve [AUC] >0.7). Survival analysis revealed that high expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM)5, CEACAM6, epidermal growth factor receptor (EGFR), stratifin (SFN), and Polo-like kinase 1 (PLK1) correlated with poor prognosis. PPI analysis confirmed these as core regulatory factors, and immune infiltration analysis revealed strong associations with dendritic cells, T cells, and macrophages. The five-gene combination yielded excellent diagnostic performance, with AUCs of 0.969 (training) and 0.971 (validation). Immunohistochemistry confirmed their elevated expression in melanoma tissues.

Conclusion: This study identified five key ARGs, CEACAM5, CEACAM6, EGFR, SFN, and PLK1, as significantly upregulated in cutaneous melanoma and associated with poor prognosis. Their combined diagnostic power suggests strong potential as clinical pathological biomarkers.

Introduction: Lung cancer is one of the most prevalent cancers, with high mortality rate. Chemotherapy is a fundamental component of the treatment. However, the response varies among individuals.

Objective: This study investigated the association of the POLR2Ers3787016 polymorphism with lung cancer susceptibility and platinum-based chemotherapy response.

Methods: The study included 498 pulmonary carcinoma patients and 213 healthy individuals. Of these, 467 cases received at least two cycles of platinum-based chemotherapy The POLR2Ers3787016 genotyping was performed using time-of-flight mass spectrometry. Unconditional logistic regression analyses were used to evaluate the association of the genotype with pulmonary carcinoma susceptibility, as well as platinum-based chemotherapy response.

Results: The study found no statistically significant association between POLR2Ers3787016 and susceptibility to pulmonary carcinoma (additive model: adjusted OR [aOR] = 1.012, 95% confidence interval [CI] = 0.781-1.310, p=0.930; dominant model: aOR = 0.794, 95% CI = 0.518-1.217, p=0.289; recessive model: aOR = 1.303, 95% CI = 0.847-2.003, p=0.228). Logistic regression analysis demonstrated no meaningful association between POLR2Ers3787016 and the efficacy of platinum-based chemotherapy (additive model: aOR = 0.901, 95% CI = 0.688-1.181, p=0.450; dominant model: aOR = 0.900, 95% CI = 0.578-1.401, p=0.642; recessive model: aOR = 0.840, 95% CI = 0.541-1.306, p=0.439). Besides, no substantial association was found between POLR2Ers3787016 polymorphism and the 5-year overall survival.

Conclusion: Current evidence does not support POLR2Ers3787016 as a potential biomarker for predicting susceptibility to pulmonary carcinoma and the therapeutic efficacy of platinum-based chemotherapy in Chinese patients.

Introduction: Ovarian cancer (OC) ranks as the fifth most common gynecologic malignancy among women worldwide.

Objective: The present study evaluates the diagnostic potential of hematological biomarkers for the early detection and differential diagnosis of OC.

Methods: A bioinformatic analysis was performed to compare immune cell profiles in blood and tissue samples from patients with OC using data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Subsequently, a retrospective clinical study was conducted at Yichang Central People’s Hospital between January 2015 and January 2021, including three cohorts: (i) Patients with benign ovarian tumors (n= 70), (ii) Patients with OC (n= 70), and (iii) Healthy controls (n= 60). A comprehensive analysis of routine blood parameters and the tumor marker cancer antigen 125 (CA125) was performed.

Results: The findings revealed that peripheral blood immune markers exhibited superior diagnostic utility compared with tissue-based indicators. The combination of CA125 with erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio showed high accuracy in differentiating benign ovarian tumors from OC (area under the curve [AUC]: 0.87). Furthermore, a panel combining CA125 and platelet-to-neutrophil ratio showed enhanced diagnostic performance in distinguishing early-stage from advanced epithelial OC (sensitivity: 81.3%; specificity: 96.6%). Notably, the triad of CA125, ESR, and white blood cell count demonstrated strong screening performance for detecting epithelial OC (AUC: 0.941; p<0.001).

Conclusion: These results suggest that integrating CA125 with routine hematological parameters significantly enhances the diagnostic accuracy and early detection of epithelial OC compared to CA125 alone, providing a practical and cost-effective screening strategy for clinical implementation.

Introduction: The release of pharmaceutical products, including biotechnological viral vector vaccines based on adenovirus serotypes 5 and 26, requires analytical control using suitable methods for both intermediate products and the final drug formulation.

Objective: To demonstrate the stability of the vector vaccine production process against quality criteria using analytical methods and to prove the convergence of data obtained across multiple manufacturing sites.

Methods: Test samples consisted of vaccine batches from three manufacturing sites. Vaccine titer was determined via the 50% cell culture infectious dose method. Authenticity was assessed using an enzyme-linked immunosorbent assay-based biological test. Biosafety was confirmed using the plaque-forming unit assay.

Results: Eighteen samples from three manufacturing sites (six from each) were analyzed in accordance with the specification parameters. The analysis included determination of protein and DNA authenticity, capsid fullness, biosafety, and infectious titer. The authenticity of the DNA insert was also confirmed. The analyzed vaccine batches met the requirements for the content of replication-competent viral particles, proving their biosafety. The average infectious titer of the vaccine ranged from 0.92 × 107 to 4.06 × 107 vp/mL, which complies with the specification.

Conclusion: All tested samples met the established acceptance criteria. The comparability of quality control results across manufacturing sites indicates the reproducibility of the vaccine production process, a key indicator of the stability and reliability of the manufacturing technology.

Introduction: Aortic valve stenosis (AVS) is clinically associated with an increased risk of stroke and ischemic cerebrovascular events. However, previous studies on the relationship between aortic valve calcification and stroke have yielded inconsistent findings, and the causal link between ischemic stroke (IHS) and calcified AVS (CAVS) remains unclear due to confounding factors.

Objective: This study aimed to investigate the relationship between IHS and CAVS.

Methods: In the first part of the study, we explored the bidirectional causal relationship between IHS and CAVS using Mendelian randomization (MR). In the second part, we identified shared diagnostic biomarkers for the two diseases through differential gene expression analysis, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator regression. Based on these biomarkers, an artificial neural network (ANN) diagnostic model was established to aid the diagnosis of both diseases.

Results: MR analysis suggested that genetically predicted IHS was associated with an increased risk of CAVS (p=0.0003, odds ratio [OR] = 1.2701, 95% confidence interval [CI]: 1.1153-1.4465), whereas CAVS did not exert a significant causal effect on IHS (p=0.2254, OR = 0.9751, 95% CI: 0.9361-1.0158). FCGR2A, RBMS2, MAP1S, RCN3, HCK, and SLPIwere identified as shared diagnostic biomarkers for IHS and CAVS. Based on these six genes, an ANN diagnostic model was developed and demonstrated reliable diagnostic performance for both diseases.

Conclusion: Genetically predicted IHS appears to be associated with an increased risk of CAVS, while CAVS does not demonstrate a significant causal effect on IHS. FCGR2A, RBMS2, MAP1S, RCN3, HCK, and SLPIserve as shared diagnostic biomarkers for IHS and CAVS. The ANN-based diagnostic model incorporating these biomarkers showed strong predictive capability for both diseases.

Introduction: Morocco has made substantial progress in expanding human immunodeficiency virus (HIV) testing and treatment, yet longitudinal data on immuno-virologic outcomes remain limited.

Objective: We sought to define the clinical profile at presentation and analyze long-term immuno-virologic outcomes under expanding integrase inhibitor-based treatment.

Methods: We performed a retrospective analysis of patients with confirmed HIV-1 infection who initiated antiretroviral therapy at the Center of Virology, Infectious, and Tropical Diseases at the Military Training Hospital between 2017 and 2025. Demographic, clinical, immunological, and virological data were collected at baseline and throughout follow-up. Statistical analyses were conducted using the Statistical Package for Social Sciences software.

Results: Late presentation was common: 35.7% presented with Centers for Disease Control and Prevention stage C, and 41.5% had CD4 < 200 cells/μL. Women had higher baseline cluster of differentiation 4 (CD4) counts than men (416 vs. 250 cells/μL; p= 0.001), whereas men displayed higher viral loads (1.19 × 10⁵ vs. 5.51 × 10⁴copies/mL; p= 0.005). Opportunistic infections remained substantial, including cytomegalovirus (16.5%), tuberculosis (12.5%), and toxoplasmosis (5.8%). First-line therapy was initially non-nucleoside reverse transcriptase inhibitor-based in half of the patients, but rapid national adoption of updated guidelines led to 93.8% receiving dolutegravir plus two nucleoside reverse transcriptase inhibitors at the last follow-up. Viral loads declined sharply within the first month, with most patients achieving and maintaining suppression from months 6-12 onward. CD4 counts rose from a median of 279 cells/μL at baseline to 560 at year 3, peaking at 610 at year 5 before stabilizing.

Conclusion: Morocco’s transition to dolutegravir-based antiretroviral therapy has produced durable virologic control and robust immune recovery. Persistent late diagnosis, sex-based disparities, and limited access to genotyping remain major obstacles. Strengthening early testing, expanding molecular monitoring, and enhancing differentiated care services will be essential to sustain national progress.

Excessive levels of reactive oxygen and nitrogen species cause cellular injury, termed oxidative stress. This occurs due to an imbalance between the prooxidant and antioxidant capabilities of the cell. Mounting evidence suggests a strong connection between aging, oxidative stress, and age-mediated diseases, including chronic kidney disease (CKD). The global prevalence of CKD has shown an increasing trend, especially among the elderly. Under physiological conditions, homeostatic mechanisms limit oxidative stress and repair oxidant-induced damage. However, in CKD, oxidative stress is not mitigated but worsened due to the disruption of homeostasis, particularly with aging. CKD also accelerates aging through several mechanisms, including oxidative stress. In turn, oxidative stress can contribute to CKD as the principal cellular factor. Besides, CKD and its comorbid conditions can result in inflammation, oxidative stress, apoptosis, and necrosis, which stimulate premature senescence in multiple body organs. Unraveling the potential mechanisms of CKD and the role of oxidative stress in CKD pathology in aging patients necessitates an inclusive discussion of current research. In this review, we summarize previous studies and discuss the role of oxidative stress and its implications in the pathogenesis of CKD during both premature and normal aging.

Introduction: Rare pathologies in medical imaging suffer from severe data scarcity, leading to AI models with low sensitivity and high false-negative rates, resulting in missed diagnoses with potentially life-threatening consequences. Although generative adversarial networks (GANs) offer a promising solution by generating synthetic images, no empirically derived quality thresholds currently exist for safe clinical deployment.

Objective: To systematically evaluate DCGAN, WGAN-GP, and StyleGAN for generating clinically useful synthetic chest X-rays, focusing on false-negative reduction and establishing clinical quality thresholds.

Methods: Using the NIH Chest X-ray dataset (89,139 images; 14 pathologies), three GAN architectures were trained to augment underrepresented classes. Evaluation included quantitative metrics (FID and structure-specific SSIM), diagnostic performance across three datasets, blinded radiologist review (n= 5; 100 images per model), and failure analysis quantifying false-negative rates.

Results: StyleGAN outperformed alternatives (FID = 18.2 vs. DCGAN: 45.6; WGAN-GP: 23.4), achieved SSIM of 0.92 (vs. 0.78 and 0.85), and preserved lung patterns at 0.90 (vs. 0.74 and 0.82). Sensitivity increased from 79.5% to 94.2%, yielding approximately 10 additional early detections per 100 rare pathology cases. StyleGAN reduced false negatives for small nodules to 12% compared to 28% for DCGAN—a 16% absolute reduction, translating to 160 additional correct diagnoses per 1,000 high-risk screenings. Radiologists rated StyleGAN images 4.7/5 (vs. DCGAN: 2.8/5). This study proposes the first empirically derived clinical quality thresholds for synthetic chest X-rays: FID < 20, SSIM > 0.90, small-structure SSIM > 0.85, and radiologist score > 4.5/5. Only StyleGAN met all criteria.

Conclusion: High-quality GANs, particularly StyleGAN, significantly reduce false negatives and improve rare pathology detection. By directly linking synthetic image quality to measurable reductions in false negatives, this study establishes clinically actionable safety thresholds and provides a regulatory-aligned framework for responsible deployment of GAN-augmented medical imaging systems.

Introduction: Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 75% of bladder cancer cases and demonstrates substantial variability in recurrence and progression. Bacillus Calmette-Guérin (BCG) is the recommended adjuvant intravesical therapy in intermediate- and high-risk tumors; however, shortages and contraindications necessitate alternative treatments. Hyperthermic intravesical chemotherapy (HIVEC) has been mainly studied with mitomycin C, and data on epirubicin-based HIVEC are limited.

Objective: This study evaluated first-line epirubicin-based HIVEC in BCG-naive patients with NMIBC.

Methods: In this study, we included and retrospectively analyzed BCG-naive patients from our prospectively recorded, multicenter HIVEC database who received HIVEC in a first-line setting between March 2017 and September 2022. Treatment included six weekly induction instillations followed by six monthly maintenance instillations. The primary outcome was recurrence-free survival (RFS), while secondary outcomes included progression-free survival, extravesical RFS, disease-free survival, cancer-specific survival, and the need for radical cystectomy.

Results: Twenty-three patients with intermediate-, high-, or very high-risk NMIBC received epirubicin-based HIVEC in a first-line setting. The median follow-up was 35 months (IQR 29-52). Two patients (8.7%) experienced intravesical recurrence (both carcinoma in situ). Median RFS was 35 months (IQR 26-50), with 1- and 2-year RFS rates of 100.0% and 95.6%, respectively. No patient experienced progression, extravesical recurrence, cancer-specific death, or required radical cystectomy.

Conclusion: First-line epirubicin-based HIVEC in BCG-naive patients provided durable oncological control in predominantly high- and very high-risk NMIBC. These results indicate that epirubicin-based HIVEC may represent a potential alternative when BCG is unavailable or contraindicated. However, the small sample size and observational design limit interpretability, underscoring the need for larger randomized trials to clarify the role of epirubicin-based HIVEC in this setting.

Introduction: Breast cancer constitutes the most common invasive neoplasm among women, with triple-negative breast cancer (TNBC) representing 10-20% of all cases and lacking a standardized therapeutic approach. Chemotherapy remains the cornerstone of treatment for TNBC patients.

Objective: Our research aimed to identify urinary metabolomic biomarkers capable of discerning chemotherapeutic response variability.

Methods: In this study, we utilized a nuclear magnetic resonance (NMR)-based urinary metabolomics technique to evaluate the metabolic profiles of TNBC patients exhibiting diverse chemotherapeutic responses.

Results: We found that the relative abundance of urinary metabolites effectively differentiated TNBC patients based on chemosensitivity. Multivariate receiver operating characteristic curve analysis indicated potential biomarkers indicative of chemotherapy responsiveness across three patient cohorts. Pathway analysis suggested perturbations in aminoacyl-tRNA biosynthesis; arginine, aspartate, and glutamate metabolism; and valine, leucine, and isoleucine biosynthesis in the pCR subgroup, and in arginine and proline metabolism, aminoacyl-tRNA biosynthesis, and histidine metabolism in the pathological partial response subgroup.

Conclusion: Our NMR metabolomic data suggest that urinary metabolites hold potential as predictors of chemotherapy sensitivity in TNBC patients.

Introduction: Acute ischemic stroke (AIS) is a major cause of death and disability worldwide. Thyroid hormones and ferritin are involved in neuronal recovery and iron metabolism after cerebral ischemia. However, their association with short-term functional outcomes in AIS, particularly potential sex-specific differences, remains unclear. This study investigated the relationship between thyroid hormone and ferritin levels and short-term functional prognosis in AIS patients.

Objective: This study aims to investigate the relationship between thyroid hormones and ferritin and the prognosis of patients with AIS, and to evaluate whether there is a sex-specific difference, which could provide a reference for predicting the short-term functional outcome of patients with AIS.

Methods: A total of 961 patients with AIS were recruited from January 2019 to December 2021. Patient demographic and clinical data were collected, and thyroid hormones (free triiodothyronine [FT3], free thyroxine, total triiodothyronine [TT3], and total thyroxine) and ferritin levels were measured on admission. Statistical methods, including t-test, chi-square test, logistic regression analysis, and correlation analysis, were used to analyze the predictive value of thyroid hormone and ferritin levels regarding short-term functional outcome in AIS patients stratified by sex.

Results: Lower FT3 and TT3 levels and higher ferritin levels were observed in patients with poor outcomes (p< 0.05). After adjustment for confounders, the findings revealed that TT3 was independently associated with poor short-term functional outcome (odds ratio = 0.405, 95% confidence interval: 0.203-0.807, p= 0.010). In sex-stratified analyses, TT3 levels were statistically correlated with poor outcomes among male patients, whereas free thyroxine, TT3, and ferritin were associated with poor outcomes in female patients. FT3 and TT3 were negatively correlated with modified Rankin Scale scores in both sexes, while ferritin showed a positive correlation with poor outcome only in female patients.

Conclusion: Thyroid hormone and ferritin levels can serve as potential predictors of short-term functional outcome in patients with AIS, and sex-specific differences exist in their effects.

Introduction: Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited treatment options, prompting interest in natural compounds with multi-target activity. Piperine has shown neuroprotective and anti-inflammatory potential, but its mechanisms against AD have not been fully elucidated.

Objective: This study employed a combined strategy of network pharmacology, molecular docking, and in vitroassays to explore the potential mechanisms by which piperine may modulate AD-related neuroinflammation.

Methods: Potential targets of piperine and AD-related targets were retrieved from multiple public databases. Common targets were analyzed via protein-protein interaction (PPI) network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and binding affinities were evaluated using molecular docking. For in vitrovalidation, BV2 microglial cells were stimulated with lipopolysaccharide (LPS) and treated with piperine. Cytokine (tumor necrosis factor alpha [TNF-α], IL [interleukin]-18, IL-1β) levels were measured by ELISA, and mRNA expression of key targets was assessed by qRT-PCR.

Results: A total of 134 overlapping targets were identified between piperine and AD. Core targets, including AKT1, HSP90AA1, SRC, RELA, and MAPK1, were discerned from the PPI network. KEGG enrichment analysis implicated several key pathways, such as PI3K-Akt, apoptosis, and cAMP signaling. Molecular docking simulations predicted stable binding interactions between piperine and these core targets, with binding energies all below −5.0 kcal/mol. In cellular experiments, piperine significantly inhibited the LPS-induced release of TNF-α, IL-18, and IL-1β. At the transcriptional level, piperine downregulated the mRNA expression of Src, Rela, and Mapk1while upregulating the expression of Akt1and Hsp90aa1(p< 0.05).

Conclusion: These findings suggest that piperine alleviates neuroinflammation in a microglial model, potentially by modulating a network of targets (AKT1, HSP90AA1, SRC, RELA, and MAPK1)and pivotal pathways, supporting the continued assessment of piperine as a potential anti-neuroinflammatory agent relevant to AD.

Introduction: Endocrine-disrupting chemicals (EDCs) have attracted increasing attention as potential contributors to vascular toxicity.

Objective: This study aimed to characterize the global research landscape, knowledge structure, and emerging trends in this field.

Methods: A total of 911 publications indexed in the Science Citation Index Expanded of the Web of Science Core Collection from 1997 to 2025 were analyzed using bibliometric and visualization methods to map collaboration patterns and knowledge evolution.

Results: The United States leads in both publication output and citation impact. Knowledge mapping indicates that an “exposure-mechanism-endpoint” framework is widely adopted in the literature, with “oxidative stress” appearing as a highly connected keyword linking environmental exposures and vascular outcomes. Trend analysis further suggests a shift in research focus from traditional persistent organic pollutants to emerging contaminants associated with modern lifestyles, alongside an increasing focus on early-life exposures and susceptible populations.

Conclusion: Research on EDC-related vascular toxicity is evolving toward greater emphasis on emerging contaminants, critical exposure windows, and mechanistic exploration. These trends may help inform future research directions and risk assessment strategies.

Introduction: Cancer cachexia is a multifactorial syndrome characterized by weight loss, skeletal muscle wasting, and systemic inflammation. Tumor necrosis factor-alpha (TNF-α) plays a central role in cachexia pathophysiology; however, the anti-inflammatory effects of endurance exercise in lung adenocarcinoma-associated cachexia remain insufficiently defined.

Objective: This study aimed to investigate the effects of endurance training on systemic inflammation, as assessed by circulating TNF-α levels, and cachexia-related outcomes in a murine orthotopic model of lung adenocarcinoma.

Methods: Male BALB/cAJcl-nu/nu mice were assigned to four groups: non-exercise control, exercise control, non-exercise lung adenocarcinoma cachexia, and exercise lung adenocarcinoma cachexia (n= 6 per group). An orthotopic lung adenocarcinoma model was established by trans-airway implantation of A549 cells. Endurance training was performed at 20 m/min for 30 min, five days per week for six weeks. Body weight, gastrocnemius wet weight, circulating TNF-α levels, and lung macroscopic and histological findings were evaluated. Data were analyzed using one-way and two-way analyses of variance.

Results: After six weeks, tumor-bearing mice exhibited significant body weight loss and skeletal muscle atrophy compared with controls, confirming successful induction of cachexia. Endurance training partially attenuated body weight loss in tumor-bearing mice. Macroscopic and histological analyses confirmed lung tumor presence in both non-exercise and exercise cachexia groups. Circulating TNF-α levels were significantly elevated in tumor-bearing mice compared with controls; notably, endurance training significantly reduced TNF-α levels in cachexia mice. Two-way analysis revealed significant main effects of tumor burden and exercise on TNF-α levels.

Conclusion: Endurance training attenuates systemic TNF-α elevation in a murine model of lung adenocarcinoma cachexia without suppressing tumor establishment. These findings support endurance exercise as a supportive anti-inflammatory strategy in cancer cachexia.

Anxiety and depression are highly prevalent among patients with cancer and negatively affect quality of life, treatment adherence, and clinical outcomes. The Hospital Anxiety and Depression Scale (HADS) is widely used in oncology due to its brevity and limited overlap with somatic symptoms. However, its psychometric performance varies across cultural and clinical settings, requiring context-specific evaluation. This study summarizes and compares evidence regarding the psychometric properties, factor structure, and clinical utility of the HADS in adult patients with cancer, and identifies gaps in cross-cultural validation, particularly the absence of an Albanian version. A narrative review of studies was conducted using major electronic databases. Validation studies, cross-cultural adaptations, systematic reviews, and meta-analyses assessing the HADS in patients with cancer were included. Evidence on reliability, validity, factor structure, and diagnostic performance was synthesized descriptively. Across diverse patient populations with cancer, the HADS demonstrated acceptable to excellent internal consistency, with Cronbach’s α values generally exceeding 0.70 for both subscales. Most studies supported the original two-factor structure, although alternative models were reported in some cultural contexts. Meta-analytic findings indicated moderate to good diagnostic accuracy for detecting clinically significant anxiety and depression. Numerous language adaptations confirmed its international applicability; however, variability in optimal cut-off scores and factor structures was observed. No validated Albanian version for cancer patients was found. The HADS is a reliable and practical screening tool in oncology. The absence of a validated Albanian version highlights the need for culturally adapted psychometric studies to support effective psychosocial screening in Albanian-speaking cancer populations.

Introduction: Bladder cancer (BC) is frequently marked by high recurrence and progression rates, making close follow-up essential. Cystoscopy remains the standard method for surveillance; however, it is invasive, costly, and uncomfortable for patients. Given these limitations, there is increasing interest in identifying minimally invasive biomarkers to support clinical management.

Objectives: This study aims to assess the potential prognostic role of the creatinine-to-hemoglobin ratio (CHR) in individuals with BC.

Methods: A retrospective study was performed on 148 patients with BC treated at the Urology Department of Mureș Clinical County Hospital. Patients’ clinical, pathological, and laboratory data were collected. CHR was calculated from routine blood test parameters. The association between CHR and tumor-related parameters was assessed using statistical testing, primarily employing non-parametric methods and Spearman’s rank correlation analysis.

Results: Elevated CHR values were significantly associated with more advanced tumor stages (median CHR: 0.10 in pT2 vs. 0.07 in pTa; p < 0.001), lower hematocrit levels, and higher tumor grades. CHR demonstrated weak but statistically significant correlations with tumor stage (r = 0.274), grade (r = 0.274), and patient age (r = 0.16). No significant association was observed between CHR and tumor size.

Conclusion: As a marker derived from routine laboratory tests, CHR may provide useful information for the assessment of BC patients, particularly those with advanced disease features. CHR appears to be associated with adverse pathological characteristics and may serve as a supportive indicator of disease burden. These preliminary findings emphasize the need for further prospective studies to determine whether CHR could be integrated into existing risk assessment tools and follow-up strategies.

Introduction: Antimicrobial resistance poses an escalating global health threat, driving the need for alternative therapeutic strategies beyond conventional antibiotics. Despite extensive preclinical research, the clinical performance of these agents remains incompletely characterized.

Objective: This systematic review and meta-analysis synthesize and evaluate clinical efficacy, safety, and pharmacologic determinants of antimicrobial peptide therapeutics in human studies, and determine their comparative performance against standard-of-care treatments.

Methods: A comprehensive search of PubMed, Embase, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform identified eligible clinical studies published between January 2000 and January 2026. Randomized controlled trials and comparative clinical studies reporting clinical or microbiologic outcomes were included in the quantitative meta-analysis. Early-phase, single-arm, or non-comparative studies were synthesized qualitatively. A random-effects model was used to estimate pooled risk ratios (RRs) for clinical cure, and heterogeneity was assessed using the I² statistic.

Results: Six comparative clinical studies involving 1,418 participants were included in the meta-analysis. Pooled analysis demonstrated no statistically significant difference in clinical cure between peptide-based therapeutics and standard-of-care treatments (RR 1.06, 95% confidence interval: 0.97-1.17), with moderate heterogeneity (I² = 64.7%). Early-phase and single-arm studies reported high clinical cure rates, particularly in biofilm-associated or localized infections. Subgroup analyses indicated that topical or locally-administered peptides produced more consistent therapeutic outcomes, whereas systemic administration showed greater variability and was more frequently limited by toxicity.

Conclusion: Antimicrobial peptides demonstrate promising activity in specific clinical contexts, particularly biofilm-related and drug-resistant infections. While current evidence does not show superiority over standard-of-care therapies, early-phase data highlight their potential in niche indications. Future development should prioritize optimizing therapeutic index, improving targeted delivery strategies, and designing infection-specific clinical trials to fully realize the clinical potential of this emerging therapeutic class.

Atypical hemolytic uremic syndrome (aHUS) is an uncommon but potentially fatal form of thrombotic microangiopathy driven by dysregulation of the alternative complement pathway, frequently linked to genetic alterations affecting complement-regulatory proteins. Its clinical presentation is heterogeneous and overlaps with other thrombotic microangiopathies, frequently delaying diagnosis and increasing the risk of irreversible organ damage. Advances in complement biology have substantially improved understanding of disease mechanisms and enabled the development of targeted C5 inhibitors, which have transformed patient outcomes. This review summarizes current knowledge regarding the epidemiology, genetic landscape, pathophysiology, clinical manifestations, diagnostic approach, and contemporary management of aHUS, with particular emphasis on complement inhibition strategies. The discussion is contextualized by a representative clinical case illustrating real-world diagnostic complexity, systemic involvement, and therapeutic decision-making. Evidence indicates that both eculizumab and ravulizumab provide effective and sustained complement blockade, with ravulizumab offering extended dosing intervals and potential advantages in treatment burden and patient preference. Despite therapeutic progress, important challenges remain, including early recognition, interpretation of complex genetic findings, determination of optimal treatment duration, and discontinuation strategies. Continued research and improved epidemiological surveillance are essential to refine risk stratification and optimize long-term outcomes in this rare but severe complement-mediated disorder.

Introduction: Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition following herpes zoster. Despite established guidelines, real-world management patterns remain poorly defined in Saudi Arabia.

Objective: To assess physician involvement, treatment practices, and perceived barriers in PHN management in the Tabuk region.

Methods: A cross-sectional survey was conducted among 113 physicians from multiple specialties. The questionnaire evaluated clinical involvement, use of pharmacologic and topical therapies, referral patterns, and psychosocial assessment practices. Descriptive statistics and categorical tests were applied.

Results: Only 36.3% of physicians reported routine involvement in PHN care, with significant variation across specialties (p< 0.001). Participation was highest among pain/palliative specialists (85.7%), neurologists (66.7%), and dermatologists (47.1%). Awareness of topical therapies was high (92.9%), but clinical use was lower (68.3%). Gabapentinoids (87.8%), tricyclic antidepressants (73.2%), and opioids (63.4%) were commonly prescribed. Key barriers included inefficient referral systems (70.7%), limited access to interventional procedures (68.3%), and lack of standardized protocols (61.0%). Although 95.1% recognized PHN’s quality-of-life impact, only 39.0% routinely assessed psychosocial burden.

Conclusions: PHN management in Tabuk shows limited physician involvement and systemic barriers. Despite high awareness of guidelines, implementation gaps persist, particularly in the use of topical therapy and psychosocial care. Strengthening referral systems and multidisciplinary approaches may improve care delivery.

Introduction: In Bulgaria, the absence of comprehensive national data poses challenges for both clinicians and healthcare authorities.

Objectives: The aim of this retrospective study was to analyze the epidemiological characteristics of inflammatory bowel disease (IBD) over a 10-year period at a leading university referral center serving the northeastern, north-central, and southeastern regions of Bulgaria.

Methods: A total of 722 adult patients aged 18-75 years were included in the cohort. All patients were treated over a 10-year period at the Referral IBD Center of the Clinic of Gastroenterology, University Multiprofile Hospital for Active Treatment “St. Marina,” Varna, Bulgaria.

Results: In the northeastern region of Bulgaria, the mean annual crude incidence was 1.72 per 100,000 population, and the mean annual crude prevalence during 2013-2022 was 13.86 per 100,000. In the north-central region of Bulgaria, the mean annual crude incidence was estimated at 0.41 per 100,000 population, and the mean annual crude prevalence during 2013-2022 was 3.12 per 100,000 population. In the southeastern region of Bulgaria, the mean annual crude incidence was 0.15 per 100,000 population. During the 2013-2022 period, the annual prevalence in this region ranged from 0.95 to 1.90 per 100,000 population.

Conclusion: The results of the present study indicate a consistent trend of increasing incidence of IBD, which is likely due both to a genuine rise in disease prevalence and to advancements in diagnostic technologies. This study provides valuable data on the epidemiology of IBD for the first time in Bulgaria.

Periodontitis is a chronic inflammatory disease that leads to progressive destruction of the tooth-supporting tissues, while conventional clinical parameters mainly reflect past tissue damage and provide limited information on current disease activity. This review aims to critically summarize current evidence on salivary and inflammatory biomarkers associated with the onset, progression, and monitoring of periodontitis, with particular emphasis on their clinical applicability and current limitations in periodontal practice. A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases. Priority was given to systematic reviews, meta-analyses, longitudinal clinical studies, and clinically relevant human studies published in English that addressed salivary inflammatory biomarkers in relation to periodontal disease activity, diagnosis, progression, and treatment monitoring. Evidence indicates that salivary cytokines, chemokines, matrix metalloproteinases, acute-phase proteins, and oxidative stress markers are associated with periodontal inflammation and tissue destruction. Among these, IL-1β, IL-6, TNF-α, and MMP-8 show the strongest associations with disease activity and treatment response. Although salivary biomarkers demonstrate strong biological associations with periodontal inflammation, heterogeneity among studies and lack of standardized diagnostic thresholds currently limit their routine chairside implementation. Further well-designed longitudinal studies are required to facilitate clinical translation.