Transmembrane serine protease 6 (TMPRSS6) gene polymorphisms have been associated with alterations in iron status and hematological parameters linked to iron homeostasis. Among the reported TMPRSS6 variants, rs855791 (c.2207 T > C; p.V736A) is the most consistently replicated and the only common variant with a demonstrated functional effect on iron metabolism. This study was conducted to analyse the impact of TMPRSS6 (rs855791) gene polymorphism on serum ferritin level and erythrocyte indices in a pediatric cohort evaluated for anemia, comprising children with and without iron deficiency anemia (IDA). TMPRSS6 (rs855791) genotyping was performed in 282 children suspected of anemia. Clinical data, complete blood counts and serum ferritin were recorded, and associations between genotypes (including dominant and recessive models), hematological parameters and iron status were assessed. Children were categorized on the basis of serum ferritin level into IDA (n = 70) and non-IDA (n = 212) groups. The genotype and allele frequencies did not differ significantly between the two groups, indicating no association between rs855791 and the risk of IDA. Serum ferritin was lowest in the ‘TT’ genotype, intermediate in ‘TC’ and highest in ‘CC’, following a graded (allele-dose) pattern, and mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were nominally lower in the ‘TT’ genotype. In the pre-specified age- and sex-adjusted additive models, each additional ‘C’ allele was associated with higher ferritin, MCV, MCH and hemoglobin, and these associations withstood Benjamini–Hochberg correction (all q ≤ 0.042), whereas the unadjusted three-genotype comparisons did not (q = 0.052–0.087). In conclusion, in this pediatric cohort TMPRSS6 (rs855791) showed evidence of association with serum ferritin, the erythrocyte indices MCV and MCH, and hemoglobin as continuous traits—most convincingly as an allele-dose trend in multivariable models—rather than with the risk of IDA itself.
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of reproductive age and is associated with reproductive dysfunction, chronic low-grade inflammation, and metabolic disturbances. However, the extent to which hematological and biochemical abnormalities vary across different body mass index (BMI) categories has not been adequately investigated, limiting our understanding of the independent contributions of adiposity and PCOS to these alterations. This case–control study included 191 women diagnosed with PCOS using Rotterdam criteria and an equal number of age-matched apparently healthy controls. Complete blood count, renal function, liver function, and lipid profile parameters were compared between groups. In the present study we found that women with PCOS exhibited significantly higher white blood cell count, hematocrit, mean platelet volume, granulocyte percentage, urea, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and liver enzyme levels (AST, ALT, and ALP), along with significantly lower high-density lipoprotein cholesterol and serum albumin compared with controls (all p values < 0.05). BMI-stratified analyses revealed that overweight/obese women with PCOS had the most pronounced hematological and metabolic abnormalities. However, unlike controls, significant alterations in the indicators of inflammatory and metabolic dysfunction were also observed in normal-weight and lean women with PCOS. These findings suggest that such disturbances may represent inherent features of the syndrome, rather than consequences of obesity alone.
Analytical-phase errors, although less frequent than pre-analytical errors, can directly compromise result accuracy and patient safety. Failure Modes and Effects Analysis (FMEA) is a recommended prospective risk-management tool, but longitudinal data from medium-volume Indian laboratories remain limited. No prospective longitudinal studies evaluating FMEA impact in this setting were identified at study initiation. To apply a structured FMEA framework with Hazard Score stratification, implement targeted Corrective and Preventive Actions (CAPA), and quantify the change in analytical-phase error rates over 12 months. A 12-month prospective before-and-after intervention study was conducted at a medium-volume NABL-accredited (NABL 128) private diagnostic laboratory in urban western India processing 51,000 tests annually. Five analytical-phase failure modes were scored using a simplified two-factor FMEA model (Hazard Score = Severity × Probability; each 1–3, maximum 9), stratified as Low (1–2), Medium (3–5), or High (6–9). Pre- and post-CAPA error rates were compared using chi-square with Yates’ correction and Fisher’s exact test. Analytical errors decreased from 21 (4.1 per 10,000 tests; 4.8 Sigma) pre-CAPA to 5 (1.0 per 10,000 tests; 5.2 Sigma) post-CAPA—a 76
Pharmacogenomic (PGx) factors significantly influence the efficacy and safety of antipsychotic treatment in schizophrenia. However, high reagent costs and complex infrastructure limit routine clinical implementation in resource-constrained settings. A single-platform, low-cost tetra-primer ARMS-PCR genotyping workflow was optimized for 20 single nucleotide polymorphisms (SNPs) across 7 key pharmacogenes (DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2). Target SNPs were shortlisted based on PharmGKB evidence levels and South Asian allele frequencies. Primers were designed using NCBI Primer-BLAST and PRIMER1. PCR standardization was performed using Platinum II Taq Hot-Start DNA Polymerase, and analytical performance was evaluated against Sanger sequencing across 20 human DNA samples. The optimized tetra-primer ARMS-PCR assays demonstrated clear, reproducible band separation on 2
Quercetin (3,5,7,3′,4′-pentahydroxy flavone) is a flavanol that is widely distributed in fruits and vegetables. Apples, onions, scallions, broccoli, and teas all contain it. It has pleiotropic health benefits with some reports suggesting that it can modulate appetite. This research examines the effectiveness of Quercetin supplementation in addressing age-related metabolic issues in a rat model of accelerated senescence. Aged rats showed poor appetite regulation, marked by increased leptin levels and decreased ghrelin levels, along with signs of insulin resistance, lipid abnormalities, and liver dysfunction. Supplementation with Quercetin helped to correct hormonal alterations, improve insulin sensitivity, and restore plasma lipid and liver enzyme profiles to healthier ranges. Four groups of Wistar rats (Rattus norvegicus) were taken, Group I (fed on standard diet), Group II (Quercetin treated with oral dose of 100 mg/kg b.w.) Group III (accelerated aging model with D-galactose, 300 mg/kg b.w, subcutaneous), Group IV (Quercetin + D-gal) for 28 days. The biochemical parameters were evaluated after rats were sacrificed. Quercetin supplementation regulated hormonal equilibrium, enhanced antioxidant defences, and mitigated inflammation associated with aging, thereby highlighting the potential of Quercetin as an anti-aging agent which may act via appetite regulation and calorie restriction. Our study suggests the impact of natural substances like Quercetin (QCN) in the regulation of metabolic homeostasis and reduction of age-related issues through appetite regulation.
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage destruction, low-grade inflammation, and oxidative stress. Emerging evidence suggests that immunometabolic pathways, particularly the tryptophan–kynurenine axis, may contribute to OA pathogenesis. This study aimed to investigate oxidative stress parameters, inflammatory cytokines, and tryptophan metabolism in patients with OA. In this cross-sectional study, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-36 alpha (IL-36α), neopterin, tryptophan, and kynurenine were measured in patients with OA and healthy controls. The kynurenine/tryptophan (KYN/TRP) ratio was calculated as an indirect marker of indoleamine 2,3-dioxygenase-1 (IDO-1) activity. Statistical comparisons between groups were performed to assess potential associations. Serum MDA and IL-36α levels were significantly higher in the OA group compared with controls (p = 0.013 and p = 0.015, respectively). In contrast, serum tryptophan levels were significantly lower in OA patients (p = 0.025). No statistically significant differences were observed in SOD, CAT, kynurenine, neopterin, tumor necrosis factor-alpha (TNF-α) levels, or the KYN/TRP ratio (p > 0.05). These findings suggest that oxidative stress and IL-36α–mediated inflammatory pathways may play a more prominent role in OA pathogenesis than classical systemic inflammatory markers. Reduced tryptophan levels without significant kynurenine pathway activation indicate limited systemic interferon gamma (IFN-γ)–IDO–mediated immune activation in OA. MDA and IL-36α may represent potential candidate biomarkers for disease monitoring. Larger longitudinal studies are required to confirm these observations.
NABL (National Accreditation Board for Testing and Calibration Laboratories) accreditation, aligned with ISO 15189 standards, is fundamental for quality assurance in clinical laboratories. Structured training of laboratory technicians during preparation for accreditation is critical for shaping compliance-related attitudes and quality culture. While evidence from private-sector institutions exists, data from tertiary care academic institutions remain limited. A pre–post interventional study was conducted among 30 laboratory technicians at the Department of Laboratory Medicine of a tertiary care academic institution in New Delhi, India. A validated 10-item questionnaire assessing attitudes was administered before and after NABL accreditation training. Responses were scored on a 3-point ordinal scale (1 = best, 3 = worst), and the Stuart–Maxwell test for marginal homogeneity was used to assess changes in attitude distribution for each item. Significant improvements were observed across all 10 questionnaire domains following training. The proportion of participants selecting the most favourable response increased from 20 to 56.7
Osteoporosis and osteopenia are major public health concerns characterised by a progressive loss of bone mineral density (BMD) and an increased risk of fractures. Conventional diagnostic approaches primarily rely on BMD assessment, and it does not adequately reflect underlying molecular changes. Proteomics may help in identifying candidate biomarkers of bone loss. In this study, serum samples from 150 age-matched individuals categorised as control, osteopenia, and osteoporosis based on dual-energy X-ray absorptiometry (DXA) T-score was analysed. Label-free quantitative (LFQ) proteomics was performed using Orbitrap-based LC–MS/MS. Pooled serum samples from each group underwent protein extraction, SDS-PAGE validation, and high-resolution mass spectrometric analysis. Differential protein expression was evaluated using fold change and log fold change (LogFC) metrics. A total of 2956 proteins were identified across all groups, indicating extensive proteomic coverage. Comparative analysis revealed significant dysregulation of proteins in osteopenia and osteoporosis, with more pronounced alterations in advanced disease. Key upregulated proteins included matrix metalloproteinase-21, pro-opiomelanocortin, and vasopressin receptor, while Ras-related C3 botulinum toxin substrate 3 (RAC3) and proteins involved in DNA repair and cellular regulation were markedly downregulated. Functional annotation demonstrated enrichment of pathways related to extracellular matrix remodelling, immune-inflammatory responses, hormonal signalling, and cytoskeletal organisation. Progressive proteomic changes from control to osteopenia and osteoporosis highlight early molecular shifts preceding severe bone loss. Orbitrap-based serum proteomics reveals systemic molecular alterations associated with declining BMD. These findings support the potential of proteomic signatures to improve early diagnosis, risk stratification, and therapeutic monitoring of osteoporosis. Further validation in larger cohorts is warranted to establish clinical applicability.
Isovaleric acidemia (IVA) is a rare autosomal-recessive disorder of leucine metabolism caused by biallelic IVD variants. Clinical phenotypes range from acute neonatal onset to asymptomatic biochemical forms. Diagnosis relies on elevated isovaleryl carnitine (IVC) in blood, isovaleryl glycine (IVG) in urine, and molecular testing. We describe an 8-year-old boy with intermittent IVA who developed acute metabolic decompensation after ingesting 250 g of butter. At age 4, he presented with encephalopathy, vomiting, abdominal pain, metabolic acidosis, and ketosis, but normal ammonia. History included a sibling’s neonatal death with pneumonia and encephalopathy. Biochemical testing revealed elevated IVC and IVG. Whole-exome sequencing showed compound heterozygosity for a novel c.1043A > T (p.Asp348Val) variant and a reported c.1222G > A (p.Glu408Lys), both predicted pathogenic. A systematic PubMed and gray-literature review identified 119 genetically confirmed IVA cases; combined with our patient, 120 cases were analysed for demographic, clinical, biochemical, radiologic, and genetic data. Majority of 120 cases (60
Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin–angiotensin–aldosterone system (RAAS). Hence, genetic variants within ACE2 can influence individual susceptibility to hypertension. This study investigates the association of rs2285666 and rs879922 within ACE2 with hypertension in Bangladeshi population. In this cross-sectional case-control study, the genotypic and allelic frequencies of rs2285666 and rs879922 were determined in 351 individuals (Normotensive = 161, Hypertensive = 190) using PCR-RFLP. Univariate and multivariate logistic regression analyses were conducted to investigate the association of genotypic distributions of these variants with hypertension. The T allele of rs2285666 was found to be significantly associated with hypertension in male participants after adjusting for age and BMI [ORa (95
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, driven by both modifiable factors (lifestyle and environment) and non-modifiable factors (age and genetics). Increasing evidence highlights epigenetic dysregulation as a key mechanism in CRC initiation and progression, emphasizing the need for reliable molecular biomarkers for early detection and prognosis. In this study, we investigated the expression profiles of key long non-coding RNAs (lncRNAs)—CCAT-1, EPHA7, and NBAT-1—and microRNAs (miRNAs)—miR-21, miR-372, miR-760, and miR-145—in an Egyptian cohort comprising 390 CRC patients and 180 healthy controls. Patients were classified into stages I–IV, and biochemical parameters were assessed. Gene expression levels were quantified using SYBR Green real-time qPCR to evaluate their diagnostic and prognostic relevance across disease stages. Our results revealed a consistent epigenetic pattern associated with CRC progression. CCAT-1 and EPHA7 were significantly upregulated in CRC patients, whereas NBAT-1 was markedly downregulated across all stages (I–IV). Among miRNAs, miR-21 and miR-372 showed significant upregulation in specific stages, while miR-760 and miR-145 were consistently downregulated compared with controls. Additionally, Chitinase-3-like protein 1 (YKL-40) was significantly elevated in CRC patients, particularly in advanced stages (III and IV), indicating its association with tumor aggressiveness. Collectively, these findings demonstrate that a combined panel of CCAT-1, EPHA7, NBAT-1, miR-21, miR-372, miR-760, miR-145, and YKL-40 may serve as a powerful diagnostic and prognostic tool in CRC. This multi-marker signature offers improved potential for early detection, disease stratification, and clinical monitoring in CRC patients.
The alpha kinase family, encompassing ALPK1, ALPK2, and ALPK3, has been associated with a variety of biological processes, including DNA repair and cell division. Nevertheless, the alterations in the expression of these genes and their correlations with the development and progression of colorectal cancer (CRC) remain relatively understudied. In this study, the potential of the alpha kinase family, including changes in expression and associated pathways, in CRC development and malignancy was the primary focus. The differential expression of ALPK1, ALPK2, and ALPK3 in CRC and their correlation with clinical characteristics and patient survival were examined using TCGA data. The protein expression levels associated with them were examined in CRC samples. To investigate the relationship between candidate gene expression and immune infiltration characteristics, the TIMER2.0 database was used. Co-expression network analysis was employed to explore potential pathways associated with the candidate genes. Fifty CRC samples, along with 50 adjacent normal tissue samples, were used for further validation by RT-qPCR. A significant increase in mRNA and protein levels of ALPK2 and ALPK3 was observed in CRC samples. ALPK3 expression was associated with clinical features, including stage IV and TNM N2, and with poorer patient prognosis. Additionally, the results indicated that ALPK2 and ALPK3 expression levels were specifically associated with immune infiltration, particularly by cancer-associated fibroblasts and neutrophils. Co-expression network analysis also revealed strong correlations between ALPK2 and ALPK3 and genes associated with the main metastatic pathway (Epithelial-Mesenchymal Transition). RT-qPCR results showed that ALPK2 and ALPK3 expression levels were significantly higher in CRC samples than in adjacent normal tissue. ALPK2 and ALPK3 are overexpressed in CRC and may be associated with metastatic pathways and immune infiltration. These findings suggest that ALPK2 and ALPK3 may have potential relevance as diagnostic and therapeutic targets in CRC; however, further experimental and clinical validation is required.
Vitamin C, scientifically known as ascorbic acid, is structurally related to glucose. The physical, biological, and chemical functions of Vitamin C are due to its electron-donor nature. Ascorbate readily undergoes autoxidation, generating hydrogen peroxide at a specific pH. In vitro studies reveal that Vitamin C functions as an antioxidant at low concentrations; however, it is pro-oxidant at high concentrations. Thus, ascorbic acid has cytotoxic effects on cancer cells. Clinical trials evaluating high-dose intravenous L-ascorbic acid have yielded mixed and, in some cases, inconclusive results. This review article covers the following aspects related to Vitamin C, such as the significance and metabolism of Vitamin C, association of Vitamin C with various types of cancer, epigenetic treatment and role of Vitamin C in epigenetic, recent clinical and preclinical studies related to Vitamin C, Anti-carcinogenic mechanism of Vitamin C, safety and toxicity associated with ascorbic acid followed by concluding remarks.
The oxidative stress and impaired antioxidant defence play a critical role in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). Genetic polymorphisms in antioxidant enzyme genes may alter enzyme activity and increase susceptibility to oxidative damage. The case-control study evaluated the polymorphisms in + 35 A/C SOD1, − 198 C/T GPx1, C−262T CAT polymorphism to assess the risk of nephropathy in T2DM patients. A total of 150 participants, including T2DM patients with DN and healthy controls, were enrolled. Genotyping of the selected SNPs, SOD1 (rs2234694), GPx1 (rs1050450), and CAT (rs1001179), was performed using pre-validated TaqMan assays with Real-Time PCR. Antioxidant enzyme activities in red blood cells were assessed using enzyme-linked immunosorbent assay (ELISA). Patients with DN showed significantly reduced GPx (P = 0.001) and SOD (P = 0.003) activities compared to controls. The CC genotype of SOD1 (OR = 3.9, P = 0.002) and TT genotype of GPx1 (OR = 2.6, P = 0.019) was associated with an increased risk of nephropathy. The T and C allele in both genes conferred higher susceptibility. CT + TT genotypes of CAT were linked to macroalbuminuria. The TTC haplotype and a high genetic risk score were significantly associated with DN (P = 0.002). Polymorphisms in SOD1 and GPx1genes and a higher genetic risk score are significantly associated with DN in T2DM, likely through reduced antioxidant enzyme activity.
Obesity is often associated with changes in vascular, metabolic, and chronic inflammatory processes resulting in metabolic syndromes. Adipocyte dysfunction causes dyslipidemia, insulin resistance, glucose intolerance, non-alcoholic fatty liver disease (NAFLD), inflammation, and certain cancers. L-PGDS generates PGD2 and related non-enzymatic degradation products of the PGJ2 series in adipocytes and is involved in the transportation of lipophilic compounds. However, its precise physiological role in inflammation and metabolic regulation under healthy conditions remains unclear. To elucidate the relationship between L-PGDS, inflammation, and obesity, this review compiled and summarized current findings. Studies in L-PGDS knockout (KO) mice, primarily generated on the C57BL/6 genetic background, consistently demonstrate increased insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis, and obesity. L-PGDS KO mice also exhibit adipocyte hypertrophy and increased gene expression associated with lipogenesis. Conversely, overexpression of L-PGDS has been shown to attenuate adipogenesis in cultured adipocytes, sometimes independently of endogenous prostaglandin production. These findings point out the involvement of L-PGDS in the adipogenesis program and related consequences involving the PPARγ signaling pathway. Furthermore, decreased L-PGDS expression and lower plasma levels have been observed in diet-induced obesity models and insulin-resistant 3T3-L1 adipocytes. The expression level of L-PGDS seemed to reflect the inflammatory activity. Collectively, the available evidence suggests that L-PGDS deficiency may contribute to impaired adipose tissue homeostasis and obesity-associated metabolic dysfunction.
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder predisposed by both environmental and genetic factors. As a negative regulator of PI3K/AKT pathway, PTEN gene plays a critical role in regulating insulin sensitivity and glucose homeostasis. This study was carried out to investigate the association of PTEN gene polymorphisms of SNPs rs2735343; G > C and rs11202592 C > G with T2DM susceptibility and related metabolic phenotypes in the ethnic Kashmiri population. In this case-control study 586 T2DM patients and 602 healthy controls were recruited. In all participants Anthropometric and biochemical parameters; Blood glucose fasting, HbA1c, lipid profile, Insulin, HOMA-IR, and TSH were assessed. Polymerase chain reaction (PCR) followed by Restriction fragment length polymorphism (RFLP) were employed for genotype determination. Statistical analysis was performed using Jamovi version 2.3.28. The GC + CC genotype of PTEN rs2735343 (G > C) was significantly higher in T2DM patients (78.7
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder characterized by ovarian dysfunction, polycystic ovarian morphology, and hyperandrogenism. Genetic factors, including polymorphisms in microRNA (miRNAs) genes, are believed to influence its pathogenesis. This case-control study aimed to investigate the association between polymorphisms in miR-196a-2 (rs11614913), miR-146a (rs6864584), and miR-143/145 (rs41291957) and the risk of PCOS in women from Zahedan, Iran. The study comprised 286 participants: 143 women diagnosed with PCOS and 143 age-matched healthy controls. Genomic DNA was extracted from peripheral blood samples using the salting-out method. Target regions were amplified by polymerase chain reaction (PCR), and genotyping was performed by restriction fragment length polymorphism (RFLP) analysis using the enzymes MspI (rs11614913 and rs41291957) and ApaI (rs6864584). The miR-146a rs6864584 C allele significantly increased PCOS risk, with TC (OR = 2.51) and CC (OR = 2.71) genotypes conferring > 2.5-fold higher risk versus TT. Conversely, the miR-196a2 rs11614913 CT genotype showed a protective effect (42
