Background G-protein coupled receptor 43 (GPR43) mediates the biological effects of short-chain fatty acids (SCFAs) in the colon, but its role in colon cancer (CC) remains insufficiently characterized. This pilot study presents in detail a cost-effective and easily reproducible fluorescence immunohistochemistry protocol for staining GPR43 in formaldehyde-fixed, paraffin-embedded human colon tissue.Methods Using samples from patients with colon adenocarcinoma (ACC) and signet ring cell carcinoma (SRCC), we optimized staining procedures with generic reagents and a custom 3D-printed slide tray, facilitating minimal reagent usage and consistent sample coverage.Results Confocal microscopy revealed distinct GPR43 localization on the apical and basal membranes of colonocytes and goblet cells in healthy tissue. In contrast, ACC tissue exhibited diffuse, disorganized staining, while SRCC samples showed minimal receptor expression. These findings suggest a link between GPR43 expression patterns and tissue differentiation status. Additionally, we observed autofluorescence at 488 nm of eosinophils without staining, as previously reported in literature.Conclusions These findings may support prognostic assessments based on intratumoral or peritumoral eosinophil counts. The present study shows in detail an easily reproducible IHC staining method for GPR 43 in paraffin embedded tissue samples, using only generic materials and highlights its potential role as a biomarker or therapeutic target in CC.
Background: The Moroccan Good Practice Guide for Laboratory Analyses (GBEA) provides the normative framework ensuring good practices and quality assurance within clinical laboratories. While some laboratories rely solely on the GBEA as their quality assurance framework, others opt for certification or accreditation to strengthen their quality management system. This study aims to explore the status of adherence to the GBEA requirements by private clinical laboratories in the Fez-Meknes region during the second half of 2025. Methods: An exploratory cross-sectional quantitative study assessing compliance, consisting of measuring the degree of compliance of the structures investigated with a predefined regulatory framework (GBEA). The data collection period lasted six months, from July to December 2025, and statistical analyses were performed using SPSS version 20 software. Results: The participating laboratories (n=30) answered all questions. Laboratories with years of experience seem to have the highest rates, unlike laboratories with less than five years, which have the lowest rates, with p<0.001. Six laboratories had the highest rates, ranging from 92% to 100%, while the lowest compliance rates were between 50% and 54.5%. Challenging aspects for laboratories are quality control, documentation, procedures for recording equipment reagents and consumables, as well as procedures for accessing and using the premises. Conclusions: Although the GBEA is a legislative and regulatory framework covering good practice and quality assurance in Moroccan laboratories, it is intended to be reinforced by an explanatory guide on standardized procedures and processes, staff training and monitoring through scheduled audits, to help laboratories establish a culture of quality and continuous improvement.
Background Ureteral calculi are common in urological practice, and ureteroscopic holmium laser lithotripsy (HLUL) is the preferred minimally invasive treatment. However, postoperative residual fragments and inflammatory responses remain frequent. This study evaluated the efficacy of Sanjin Paishi Decoction (SJPSD) combined with phloroglucinol in promoting stone expulsion and alleviating inflammation and oxidative stress following HLUL. Methods In this prospective randomized controlled trial, 192 patients with ureteral stones were assigned to either phloroglucinol alone (control) or SJPSD plus phloroglucinol (combined). After exclusions, 183 patients (control: 92; combined: 91) were analyzed. Outcomes assessed included stone-free rates at 7 and 14 days, hospital stay, postoperative pain (VAS), inflammatory markers (CRP, TNF-alpha, IL-6), oxidative stress indices (CAT, GSH-Px, MDA, ROS), and complications. Results The combined group achieved higher stone-free rates at 7 and 14 days (87.9% and 98.9%) than the control group (65.2% and 91.3%, p < 0.05) and reduced hospitalization time (p < 0.001). Patients in the combined group reported lower VAS scores and exhibited significantly decreased inflammatory mediators (CRP, TNF-alpha, IL-6) and oxidative stress markers (MDA, ROS) at day 7 (all p < 0.05). Furthermore, the incidence of complications was lower in the combined group (2.2%) than that in the control group (11.96%) (p < 0.05). Conclusions Adjunctive SJPSD with phloroglucinol accelerates stone clearance, shortens recovery, relieves pain, and attenuates inflammation and oxidative stress, while reducing postoperative complications in HLUL patients.
Background: Systemic inflammation and hypercoagulability are key drivers of cancer progression. This study aimed to evaluate the predictive value of inflammatory and coagulation-related ratios-specifically neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-D-dimer ratio (FDR)-in patients with colorectal and pancreatic cancer. Methods: We prospectively enrolled 73 patients with confirmed colorectal (n=57) or pancreatic cancer (n=16). Patients were classified as responders (n=39) or non-responders (n=34) based on radiological evaluation 6 months post-therapy. Baseline complete blood counts, ferritin, and D-dimer levels were compared. Predictive accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results: Non-responders exhibited significantly higher baseline leukocyte and neutrophil counts (p<0.002). Ferritin levels were 2.5-fold higher in non-responders (p<0.05). ROC analysis identified NLR as a strong predictor of treatment failure (AUC=0.895; Optimal Cut-off >2.68), while LMR was a significant predictor of favorable response (AUC=0.864). Unlike previous reports, FDR was significantly elevated in non-responders (p=0.002). High NLR was moderately correlated with poor functional status (ECOG r=0.44) exclusively in the non-responder group. Conclusions: Baseline NLR and LMR are robust predictors of therapeutic outcome in colorectal and pancreatic cancer.
Background Anemia in adult males is an underrecognized condition that may reflect nutritional deficiencies, chronic disease, or inflammation. Data on the prevalence of anemia and its associated factors among adult males attending healthcare facilities in Saudi Arabia remain limited. This study aimed to determine the prevalence of anemia and identify associated demographic, lifestyle, and clinical factors among adult male patients at a Security Forces Hospital. Methods A cross-sectional study was conducted among 568 adult male patients aged >= 18 years. Blood samples were analyzed using automated hematology analyzers to assess blood count parameters. Anemia was defined according to World Health Organization criteria as hemoglobin <13 g/dL. Demographic, lifestyle, and clinical data were collected. Associations between anemia and independent variables were assessed using chi-square and independent t-tests, with p<0.05 considered statistically significant. Results The prevalence of anemia was 15.8%. Anemia increased significantly with age (p<0.001), with the highest prevalence among participants aged 55-64 years. Physical inactivity, iron supplementation use, and conception of iron-rich food were significantly associated with anemia (p<0.05). Most cases were mild (65.6%), and microcytic hypochromic anemia was the predominant morphological type (52.2%). Iron studies showed low serum iron levels in more than half of the tested participants. Conclusions Anemia is common among adult male patients, particularly in older age groups. Iron deficiency appears to be a major contributor, although multiple etiologies are likely. These findings support routine anemia screening and preventive strategies among adult males in hospital settings.
Background Besides its clinical importance, triglyceride (TG) measurement plays a critical role in calculating Low-Density Lipo-protein Cholesterol (LDL-C). Therefore, it is important to highlight any biases when changing methods. The Clinical Laboratory Standards Institute (CLSI) EP09-A3 recommends evaluating bias between two methods using fresh samples, while EP15-A3 suggests verifying precision and estimating bias, with quality control (QC) material as an option for samples.Methods The performance of three different TG reagents (Abbott Triglyceride, Abbott Triglyceride-2, and Archem Triglyceride) with EP09-A3 and EP15-A3 and the effects of TG results on LDL-C calculations were evaluated.Results Notable inconsistencies were observed between biases from patient samples and QC materials. The lowest QC measurements and the highest patient results were both seen with Abbott TG. While median bias values were within acceptable limits, there were discrepancies in slope and intercept values between TG reagents. The bias in LDL-C values calculated using Friedewald's and Sampson's equation was acceptable, but the Martin-Hopkins equation showed even less bias. The Abbott TG reagent fully met the imprecision criteria, the Abbott TG 2 reagent partially but clinically acceptably met them, whereas the Archem TG reagent, despite having imprecision values below the optimum CV, failed to meet the manufacturer's claims.Conclusions This discrepancy in bias between patient samples and QC materials underscores the challenge of control material commutability. Laboratories should assess bias when switching methods using the practical EP09-A3 approach, and perform an EP15-A3 verification study before introducing any new kit into routine use.
Background Hypercholesterolemia is a cardinal driver of atherosclerotic cardiovascular disease (ASCVD), one of the major global mortality causes. Associated oxidative stress and lipid peroxidation perturbes HDL-associated paraoxonase-1 (PON1) activity. This study investigates the effects of chronic L-arginine supplementation-a nitric oxide precursor-on PON1 activity, lipid profiles, and oxidative stress in hypercholesterolemic rats.Methods Subjects were randomly selected and divided into four equal groups (n=36): control (C), L-arginine (LA), hypercholesterolemia (HC), and hypercholesterolemia + L-arginine (HC+LA). After 8-weeks study period, serum lipid levels, PON1, and malondialdehyde (MDA) levels were measured, and the atherogenic index (ATI) was calculated. Atherosclerotic lesions were evaluated histopathologically.Results PON1, MDA, and lipid levels, as well as ATI and the PON1/HDL ratio, were increased in the HC group. These variables were significantly lower in the HC+LA group than in the HC group. Moreover, a significant increase in TG, VLDL, and PON1 levels was observed in the LA group compared with the C group. A strong negative correlation was found between PON1 and MDA levels.Conclusions Chronic L-arginine supplementation was effective in reducing ATI, LDL, and oxidative stress, and in alleviating structural vascular changes in high cholesterol diet-induced hypercholesterolemia model rats.
Background Skin injury repair depends on a tightly regulated sequence of inflammation, proliferation, and matrix remodeling, where mediators such as IL-1 and IL-6 contribute to immune activation and extracellular matrix formation. Variability in cytokine control influences scar maturation, prompting exploration of treatment strategies capable of shortening the inflammatory phase and enhancing structural regeneration.Methods This study compared four wound-care approaches in rats with surgically induced full- thickness lesions: a polysilicon-siloxane formulation (PS), a silicone-based gel (Sil), a betamethasone preparation (BMt), and a heparin-containing agent (Hep). Topical formulations were applied two to three times daily, while BMt was delivered weekly by subcutaneous injection. Serum IL-1 and IL-6 concentrations were quantified by ELISA, scar evolution was documented using the Vancouver Scar Scale, and tissue organization was examined through histological staining protocols, including trichrome-based collagen visualization and elastic fiber assessment.Results Early cytokine elevation was evident across groups, with IL-1 returning to near-baseline most rapidly in PS- and Sil-treated animals by day 21, and one week later in BMt-treated rats. Hep and untreated controls maintained higher values for longer. IL-6 peaked later than IL-1, normalizing by day 28 in the PS, Sil, and BMt groups alone. Microscopy demonstrated faster vascular normalization and earlier collagen and elastic-fiber restoration with PS, followed by Sil and BMt, while Hep improved matrix architecture only during later stages.Conclusions Overall, PS produced the most favorable and accelerated recovery pattern, Sil and BMt provided moderate benefit, and Hep displayed slower reparative capacity.
Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, characterized by hormonal, metabolic, and inflammatory changes. Chronic low-grade inflammation plays a key role in its pathogenesis. Traditional markers such as CRP and leukocyte count are often non-specific, while novel biomarkers SIRI and AISI provide a more comprehensive assessment of immune status.Methods In this comparative study, 35 women with PCOS and 45 healthy controls aged 18-40 years were evaluated. Age and BMI were comparable between groups. Serum fasting glucose, fasting insulin, lipid profile, CRP, and total testosterone were measured (Cobas pure, Roche Diagnostics), and insulin resistance was estimated via HOMA-IR. SIRI and AISI indices were calculated from complete blood count data using a Sysmex XN-1000 analyzer.Results Among women with PCOS, phenotype A was predominant (85.7%). Compared to controls, women with PCOS had higher fasting insulin, HOMA-IR, atherogenic lipid profile, CRP, total leukocyte count, total testosterone, and inflammatory indices (SIRI and AISI), while fasting glucose was similar. Both AISI and SIRI were significantly higher in PCOS (AISI median 269.4 vs. 150.1; SIRI median 0.9500 vs. 0.5600; p = 0.001). ROC analysis showed acceptable discriminatory ability (AUC 0.712 for AISI; 0.713 for SIRI), with moderate sensitivity (AISI 57.8%; SIRI 64.4%) and specificity (AISI 80%; SIRI 74.3%) for distinguishing PCOS from controls.Conclusions AISI and SIRI values are significantly higher in women with PCOS and serve as accessible, reliable biomarkers of chronic low-grade inflammation, supporting their use in routine clinical assessment for early detection of systemic inflammation.
Background Helicobacter pylori (HP) infection is a well-established risk factor for gastric carcinogenesis, primarily through the induction and maintenance of chronic gastric mucosal inflammation. In this study, we aimed to explore the correlations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) levels with the risk of gastric mucosal cancerization in patients with HP-positive gastritis. Methods Subjects (200 in total) in this retrospective study were enrolled from patients with HP-positive gastritis treated from January 2022 to December 2024. A non-cancer group (n=80, patients with chronic superficial gastritis and atrophic gastritis) and a cancer group (n=120, patients with gastric cancer) were set based on the condition of mucosal lesions. Measurement of serum TNF-alpha and IL-8 levels was completed through enzyme-linked immunosorbent assay. The 14C-urea breath test was conducted to determine the status of HP infection. Multivariate regression analysis was employed to identify the influencing factors of gastric mucosal cancerization risk. Receiver operating characteristic (ROC) curve analysis was also conducted. Results The serum TNF-alpha and IL-8 levels were significantly higher in the cancer group than in the non-cancer group (p<0.05). Both TNF-alpha and IL-8 levels displayed significantly positive correlations with the risk of gastric mucosal cancerization (r=0.785, r=0.812, p<0.05). Elevated TNF-alpha and IL-8 levels, high severity of HP infection and presence of virulence factor cytotoxin-associated gene A were independent risk factors for gastric mucosal cancerization (p<0.05). The areas under the ROC curves of serum TNF-alpha and IL-8 levels were 0.798 and 0.698, respectively (p<0.01). Conclusions This study reveals a close positive correlation between serum TNF-alpha and IL-8 levels and the risk of gastric mucosal cancerization in patients with HP-positive gastritis.
Background A maternal high-fat diet influences offspring and may elevate their susceptibility to obesity and type 2 diabetes mellitus. This study aims to examine the impact of a high-fat, high-carbohydrate diet on the development of obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease in mice and their progeny.Methods Twenty one-month-old BALB/c mice (10 males and 10 females) were divided into control and first-generation groups of five males and five females. The control mice ate a butter-based diet with 10%-11% fat calories, while the first-generation mice ate 45% fat and 30% carbohydrates. The weights of both groups were measured for 4 months. In the first generation, females and males cohabited and mated. Mothers ate a high-fat, high-carbohydrate diet throughout pregnancy and nursing. After weaning, 10 second-generation pups (five males and five females) were randomly picked and isolated from their mothers in other cages. Isolated weaned offspring ate a high-fat, high-carbohydrate diet for 4 months. Several biochemical parameters were estimated for each mouse in the three groups.Results Higher levels of random blood glucose, triglycerides, total cholesterol, and LDL-C were seen in the second generation than in the first generation, whereas lower HDL-C was observed in the second generation. The second generation had considerably greater HbA1c levels than the first generation. Significantly greater liver enzyme activity was seen in the second generation. Proteinuria was observed in the second generation. Second-generation mice had greater total CK and CK-MB activity. The second-generation group showed considerably lower nitric oxide and adropin levels than the first-generation group. The second-generation mice had greater serum endothelin-1 and vascular endothelial growth factor levels than the first-generation mice.Conclusions The study concludes that a high-fat, high-carbohydrate diet induces obesity and T2DM in mice. The offspring of mothers that consume a high-fat, high-carbohydrate diet during both prenatal and postnatal periods exhibit a greater risk of developing these diseases than their progenitors.
Background: Catheter-related bloodstream infections (CRBSIs) are a significant cause of morbidity and mortality in patients undergoing chronic hemodialysis. Identifying reliable prognostic markers is essential for early risk stratification and clinical decision-making. Methods: This retrospective study included 147 patients with end-stage renal disease receiving chronic hemodialysis via central venous catheter who were hospitalized with confirmed CRBSIs between 2020 and 2024. Demographic, clinical, and laboratory data were collected on admission and on the third day of hospitalization. Inflammatory markers such as white blood cell count (WBC), neutrophil count, mean platelet volume (MPV), and derived indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were evaluated in relation to in-hospital mortality. Results: Thirteen patients (8.8%) died during hospitalization. Age, WBC, neutrophil count, and MPV were significantly higher in the mortality group (p<0.01). While NLR and PLR on admission were not significantly different, third-day PLR values were significantly lower in non-survivors (p=0.033), showing moderate predictive performance (AUC = 0.679). Point biserial correlation and ROC analysis supported the prognostic utility of WBC, neutrophils, and PLR. Conclusions: Age, WBC, neutrophils, MPV, and third-day PLR are potential prognostic markers for in-hospital mortality in hemo-dialysis patients with CRBSIs. Dynamic monitoring of these hematologic indices may support early clinical decision-making.
Background Proliferative diabetic retinopathy (PDR) is characterized by pathological neovascularization and microvascular damage driven by hypoxia-related mechanisms. We aimed to explore the correlations of serum hypoxia-inducible factor 1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1 (SDF-1) levels with microvascular injury in patients with proliferative diabetic retinopathy. Methods Subjects (150 in total) with type 2 diabetes mellitus and diabetic retinopathy (DR) who were treated at our hospital between January 2023 and June 2024 were assigned to a proliferative DR (PDR) group (n=82) and a non-proliferative DR (NPDR) group (n=68). Comparisons were carried out on the general data, microvascular endothelial function [circulating endothelial cells (CEC), endothelial progenitor cells (EPC), and circulating progenitor cells (CPC)], and serum HIF-1 alpha, VEGF and SDF-1 between the two groups. Results High expressions of serum HIF-1 alpha, VEGF, and SDF-1 were associated with an increased risk of PDR of 2.465, 3.132, and 2.592 times, respectively (p<0.05). Serum HIF-1 alpha, VEGF, and SDF-1 were independent influencing factors for PDR (p<0.05). Areas under the curves (AUCs) of serum HIF-1 alpha, VEGF, and SDF-1 for predicting PDR were 0.721, 0.762, and 0.748, respectively. A prediction model combining serum HIF-1 alpha, VEGF, and SDF-1 was constructed: Log(P) = -0.251 + 0.271 & times; HIF-1 alpha + 0.290 & times; VEGF + 0.277 & times; SDF-1. AUCs of the triple combination for PDR prediction was 0.869, significantly exceeding the predictive values of the three indicators alone (Z=3.246, 3.172, 3.231, p=0.002, <0.001, <0.001). Conclusions Serum HIF-1 alpha, VEGF, and SDF-1 have significant correlations with microvascular injury in proliferative diabetic retinopathy patients, and their combination is highly valuable for the early identification of high-risk patients.
Background Coagulation assays such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are widely used for patient monitoring. Accurate interpretation of sequential test results requires consideration of both biological and analytical variation. The reference change value (RCV) is a statistical tool that determines whether changes in serial results are clinically significant. While RCVs are typically calculated using intra-laboratory data, inter-laboratory variability remains largely unexplored for coagulation parameters. This observational study aimed to calculate intra- and inter-laboratory RCVs for PT, INR, and aPTT. Methods Internal quality control (IQC) data and external quality assessment (EQA) results were collected monthly throughout 2024. Intra-laboratory analytical imprecision (CVA) was derived from IQC data, while inter-laboratory CVA was estimated using EQA results. RCVs were calculated using an asymmetric log-normal model incorporating within-subject biological variation (CVI) and a Z-score of 1.64. Results Intra-laboratory CVA values were 5.1% (PT), 5.3% (INR), and 3.5% (aPTT), whereas inter-laboratory CVA values were substantially higher: 21.1%, 18.1%, and 13.6%, respectively. Corresponding intra-laboratory RCV increase values were 14.2% (PT), 14.6% (INR), and 11.0% (aPTT), while inter-laboratory RCV increase values reached 63.1%, 52.5%, and 37.9%. Individuality index values were <0.6 for all tests, highlighting the limited value of reference intervals and the clinical utility of RCVs. Conclusions The findings demonstrate that inter-laboratory RCVs for PT, INR, and aPTT are substantially wider than intra-laboratory RCVs, reflecting the impact of between-laboratory analytical variability. These results emphasize the need for context-specific RCV thresholds, particularly when interpreting serial coagulation test results across different laboratories.
The interpretation of hemoglobin (Hb) values in clinical practice involves both absolute thresholds and relative changes, yet alignment between clinical decision limits (CDLs) and laboratory quality control (QC) thresholds is unclear. This study aimed to compare published CDLs for Hb used in diagnosis and treatment with those applied in laboratory internal QC processes.
Background Chromosomal translocations, particularly X-autosome rearrangements, are rare and can produce complex clinical phenotypes even in carriers who appear phenotypically normal.Case presentation We present a female patient with primary amenorrhea, hypergonadotropic hypogonadism, and recurrent major depressive episodes. Cytogenetic analysis revealed a previously unreported karyotype: 46,X,t(X;12)(Xpter -> Xq24::12p13 -> 12pter;Xqt er -> Xq24::12p13 -> 12qter). Array-CGH analysis confirmed that the translocation was balanced and no pathogenic copy number alterations were detected. As both parents' karyotypes were normal, this rearrangement arose de novo. The Xq23 region contains genes involved in neuronal activity, synaptic transmission, and behaviour regulation, such as TRPC5, HTR2C, PAK3, AMMECR1, and nearby gene PLS3. The 12p13 region, on the other hand, harbours genes associated with calcium signalling, NMDA receptor function, and neurotrophic support, such as TNFRSF1A, CACNA1C, GRIN2B, FKBP4, and NTF3. PLS3 and AMMECR1 may influence cytoskeletal structure and neuronal migration. The proximity of these loci may lead to changes in gene expression through interaction with regulatory elements. This combination may explain the possible genetic basis for the simultaneous occur-rence of gonadal insufficiency, primary amenorrhoea, and neuropsychiatric findings. Computational analyses suggest that these genes may jointly modulate neuroplasticity, hypothalamic-pituitary-gonadal axis function, and neuroinflammatory responses.Case presentation We present a female patient with primary amenorrhea, hypergonadotropic hypogonadism, and recurrent major depressive episodes. Cytogenetic analysis revealed a previously unreported karyotype: 46,X,t(X;12)(Xpter -> Xq24::12p13 -> 12pter;Xqt er -> Xq24::12p13 -> 12qter). Array-CGH analysis confirmed that the translocation was balanced and no pathogenic copy number alterations were detected. As both parents' karyotypes were normal, this rearrangement arose de novo. The Xq23 region contains genes involved in neuronal activity, synaptic transmission, and behaviour regulation, such as TRPC5, HTR2C, PAK3, AMMECR1, and nearby gene PLS3. The 12p13 region, on the other hand, harbours genes associated with calcium signalling, NMDA receptor function, and neurotrophic support, such as TNFRSF1A, CACNA1C, GRIN2B, FKBP4, and NTF3. PLS3 and AMMECR1 may influence cytoskeletal structure and neuronal migration. The proximity of these loci may lead to changes in gene expression through interaction with regulatory elements. This combination may explain the possible genetic basis for the simultaneous occur-rence of gonadal insufficiency, primary amenorrhoea, and neuropsychiatric findings. Computational analyses suggest that these genes may jointly modulate neuroplasticity, hypothalamic-pituitary-gonadal axis function, and neuroinflammatory responses.Case presentation We present a female patient with primary amenorrhea, hypergonadotropic hypogonadism, and recurrent major depressive episodes. Cytogenetic analysis revealed a previously unreported karyotype: 46,X,t(X;12)(Xpter -> Xq24::12p13 -> 12pter;Xqt er -> Xq24::12p13 -> 12qter). Array-CGH analysis confirmed that the translocation was balanced and no pathogenic copy number alterations were detected. As both parents' karyotypes were normal, this rearrangement arose de novo. The Xq23 region contains genes involved in neuronal activity, synaptic transmission, and behaviour regulation, such as TRPC5, HTR2C, PAK3, AMMECR1, and nearby gene PLS3. The 12p13 region, on the other hand, harbours genes associated with calcium signalling, NMDA receptor function, and neurotrophic support, such as TNFRSF1A, CACNA1C, GRIN2B, FKBP4, and NTF3. PLS3 and AMMECR1 may influence cytoskeletal structure and neuronal migration. The proximity of these loci may lead to changes in gene expression through interaction with regulatory elements. This combination may explain the possible genetic basis for the simultaneous occur-rence of gonadal insufficiency, primary amenorrhoea, and neuropsychiatric findings. Computational analyses suggest that these genes may jointly modulate neuroplasticity, hypothalamic-pituitary-gonadal axis function, and neuroinflammatory responses.Conclusions This case highlights the importance of cytogenetic, molecular, and computer-assisted analyses in evaluating X-autosomal translocations in patients with unexplained amenorrhoea or recurrent depressive symptoms. Furthermore, candidate genes at breakpoints emerge as potential targets for future functional and clinical studies.
Background: Pediatric headache is a common neurological condition that adversely affects quality of life. Vitamin B12 is involved in homocysteine (Hcy) and methylmalonic acid (MMA) metabolism, and nitric oxide (NO) plays a role in neurovascular signaling. This study evaluated vitamin B12-related biomarkers and NO in pediatric migraine and tension-type headache (TTH). Methods: The study included 39 migraine, 42 TTH and 29 control. Vitamin B12 and folic acid were measured using the Roche Cobas e601, Hcy were measured with the Shimadzu LC-20 HPLC, MMA were measured by a modified LC-MS/MS method, NO were measured using the Griess method. Results: Hcy levels differed significantly between the migraine and control, as well as between the TTH and control (p<0.05). For MMA, a significant difference was observed between the TTH and control groups (p<0.05). Total nitrite and nitrate concentrations were significantly higher in patients than in controls(p<0.05). Conclusions: Although serum vitamin B12 concentrations did not show a significant difference, median MMA values were elevated in the patient groups. MMA is recognized as a biomarker of subclinical vitamin B12 deficiency, and because oxidative stress may impair the cellular function of vitamin B12, MMA measurement provides valuable information even when serum B12 levels remain within the normal range. Furthermore, endothelial damage induced by Hcy, together with chronic oxidative stress associated with the Hcy-NO pathway, may contribute to the pathogenesis of pediatric migraine and TTH. Consistent with this, the significantly higher levels of NO metabolites in patients compared with controls suggest that NO may play a role in the development of migraine and TTH in the pediatric population.
Background: Chronic hepatitis B (HBV) infection causes significant morbidity. Liver biopsy, the gold standard for fibrosis assessment, is invasive, highlighting the need for non-invasive biomarkers. beta-Klotho, a transmembrane protein, may be released during hepatocyte injury. This study aimed to evaluate serum beta-Klotho in treatment-na & iuml;ve chronic HBV patients and its correlation with inflammation and fibrosis indices. Methods: Sixty-seven treatment-na & iuml;ve HBV patients were divided by viral load (<10(5) IU/mL, n=34; >= 10(5) IU/mL, n=33), with 18 healthy controls. Serum beta-Klotho was measured via ELISA. Inflammation indices (SII, SIRI, PLR, NLR, LMR, PNR) and non-invasive fibrosis indices (APRI, GAPI, API, PAPAS, others) were calculated. Spearman correlation and ROC analysis were performed. Results: Median serum beta-Klotho levels tended to be higher in patients with increased HBV DNA levels; however, no statistically significant difference or correlation was observed (p=0.052; p=0.813). Positive correlations were found with SIRI (r=0.389, p=0.001) and GAPI (r=0.270, p=0.027), negative with LMR (r=-0.269, p=0.028) and PNR (r=-0.322, p=0.008). ROC analysis showed limited diagnostic value (AUC=0.674, p=0.024), with high specificity (94.4%) but low sensitivity (46.3%). No correlation with fibrosis stage was observed. Conclusions: Serum beta-Klotho tends to increase with viral load, reflecting hepatocellular injury and systemic inflammation rather than established fibrosis. It may serve as a novel non-invasive damage-associated biomarker in chronic HBV, though diagnostic sensitivity is limited.
Background Our preliminary studies identified the arylpiperazine derivative NAF19 as a promising therapeutic agent against prostate cancer, though its precise mechanisms remained unclear.Methods Network pharmacology was utilized to pinpoint both therapeutic targets and disease-related targets. Functional assessments of cells were conducted using the CCK-8 method and wound-healing assays to analyze the effects of NAF19 on LNCaP cell proliferation and migration, respectively. The effect of NAF19 on the cell cycle progression of prostate cancer cells was examined using flow cytometry, while phosphorylation of AKT and PI3K was assessed using Western blotting.Results The anti-proliferative activity of NAF19 increased with higher doses and longer durations of treatment. The wound healing assay confirms its strong inhibitory effect on cell migration. Western blotting results indicate that NAF19 influences EMT-related protein expression, leading to elevated E-cadherin and decreased Vimentin and N-cadherin levels. Further mechanistic investigation showed that NAF19 significantly reduced the expression of CXCR4, as well as phosphorylated PI3K and Akt proteins. Western blot results confirmed that NAF19 downregulated Skp2 while increasing the levels of p27 and p21, suggesting involvement of the Skp2/p27/p21 signaling pathway. Molecular docking analysis demonstrated that NAF19 binds strongly to CXCR4, exhibiting a binding energy of -9.6 kcal/mol.Conclusions This investigation confirms that NAF19 acts as a new CXCR4 antagonist, effectively suppressing several cancer-promoting pathways in prostate cancer, such as PI3K/AKT signaling, cell cycle advancement, and EMT.
Background Atopic dermatitis (AD) is a chronic immune and inflammatory dermatologic disease. Preclinical and clinical studies have indicated that stem cell transplantation is considered an alternative treatment option for ameliorating the symptoms of AD. However, the molecular mechanisms by which stem cells treat AD remain unclear. This study aimed to evaluate the therapeutic effects of Wharton's jelly mesenchymal stem cells in a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of AD.Methods Human Wharton's jelly-mesenchymal stem cells (hWJ-MSCs) were subcutaneously injected into mice receiving DNFB on day 7 (DNFB-MSC 7 group) and days 7 and 16 (DNFB-MSC 7, 16 group).Results hWJ-MSCs improved the symptoms of AD and lowered the clinical skin score. After treatment with hWJ-MSCs, the skin thickness of the epidermis was reduced in AD mice. hWJ-MSCs decreased the serum concentration of IgE. Mechanically, hWJ-MSCs inhibited the expression of proteins associated with the NLRP3 inflammasome, such as NLRP3, ASC/TMS1, TXNIP, and caspase-1. Furthermore, hWJ-MSCs regulated the expression of TGF-beta 1 and histone deacetylase 3 (HDAC3) proteins.Conclusions Taking these results together, treatment with hWJ-MSCs improved the clinical symptoms by regulating TXNIP/NLRP3 and HDAC3/TGF-beta 1 signaling cascade.
