Indian Journal of Clinical Biochemistry最新文献

Bioinformatics is considered a powerful tool to investigate and deeply analyze large datasets. A significant quantity of data is generated by prostate cancer and dysregulation of microRNA (miRNA) in tissues and bodily fluids (serum, plasma, urine). Screening dysregulated miRNA is currently more accessible, more reliable, and more precise with the help of insilico approaches. Hence the objective of the study is to identify miRNAs and explore their mRNA interaction in prostate cancer development. Here in the present study, we analyzed the GEO dataset GSE112264 and performed GEO-2R analysis to segregate significantly upregulated and downregulated miRNAs. The targetome of each miRNA containing several target genes was analyzed and put in an interactive network form. Functional enrichment analysis using DAVID 6.8 and GSEA was carried out to get KEGG, Reactome, and GO-BP analysis. Our analysis revealed that out of 190 overlapped significant miRNAs, only 9 miRNAs (hsa-miRNA-185-5p, hsa-miRNA-211-5p, hsa-miRNA-330-3p, hsa-miRNA-342-3p, hsa-miRNA-3622b-5p, hsa-miRNA-486-5p, hsa-miRNA-520a-3p, hsa-miRNA-550a-3p, hsa-miRNA-574-3p) were found to target 20 unique target genes (AKT1, EP300, E2F1, KRAS, AR, CREB5, CCND1, CDKNA1, EGFR, ERBB2, FGFR1, FOXO1, IKBKG, IGF1R, MAPK1, PTEN, PIK3R1, and TP53) that were involved in Prostate cancer survival and proliferation. Out of 9 miRNAs, two miRNAs (miRNA-520a-3p and miRNA-550a-3p) are novel miRNAs that have yet to be explored in Prostate cancer pathogenesis. To conclude and for future research, 8 miRNAs are yet to be explored for non-invasive potential as diagnostic and prognostic biomarkers in Prostate cancer progression and development. The target genes of each miRNA could provide novel insights in developing therapeutics for better management of disease.

Subclinical hypothyroidism (SCH) is a usually asymptomatic endocrine disorder characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine (fT4) levels. The kynurenine pathway is activated during inflammation, and several of its metabolites have been proposed as potential biomarkers in inflammatory diseases. This study aims to understand the pathophysiology of the disease by investigating changes in the metabolism of kynurenine in patients with SCH and evaluating the potential of these metabolites as biomarkers. The study included 44 patients diagnosed with SCH in the endocrinology clinic and 35 healthy volunteers. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the metabolites of the kynurenine pathway. TSH, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibody levels were significantly higher in the SCH group than in the control group (p < 0.05). Tryptophan (TRP) levels were significantly lower in the SCH group, while kynurenic acid (KYNA), 3-hydroxykynurenine (3-HKYN) and 3-hydroxyanthranilic acid (3-HAA) levels were significantly higher (p < 0.05). In the ROC analysis, the KYNA/TRP ratio (AUC: 0.827, 95% CI 0.737-0.917) had the highest discriminatory power to distinguish individuals with SCH, followed by 3-HAA/TRP (AUC: 0.758, 95% CI 0.655-0.862), KYNA/kynurenine (KYN) (AUC: 0.718, 95% CI 0.604-0.833) and TRP (AUC: 0.713, 95% CI 0.594-0.833). 3-HKYN showed the highest value with a sensitivity of 86%, while the KYNA/TRP ratio stood out with a specificity of 97%. The KYNA/TRP ratio may serve as a potential biomarker candidate for SCH. The interaction of kynurenine metabolism with inflammatory processes may play a role in the development of SCH. These findings suggest that alterations in the kynurenine pathway may contribute to the pathophysiology of SCH and help to better understand the underlying mechanisms of the disease.

Disorders affecting ejaculation is only one of the many factors which may contribute to the pathogenesis of infertility. The genetic etiopathogenesis underlying anejaculation is not clear. It is important to elucidate the genetic etiology of anejaculation with respect to treatment options and genetic counseling. Herein we report two cases presenting anejaculation with familial ADRA1A missense variants. To our knowledge, this is the first report in the literature.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01210-2.

Haemoglobinopathies are genetic disorders causing abnormalities in the production, structure, or function of haemoglobin. Haemoglobin D-Punjab is a prevalent haemoglobin variant in Punjab and northwest India. Heterozygous individuals typically exhibit no symptoms, while homozygotes may experience mild to moderate haemolytic anaemia. While, beta thalassaemia trait decreases beta-globin synthesis, occasionally causing moderate anaemia. Gilbert's syndrome, a common cause of unconjugated hyperbilirubinaemia without haemolytic symptoms occurs due to reduced uridine glucuronyl transferase enzyme activity. Coexistence of Hb D-Punjab/β-thalassaemia and Gilbert's syndrome is rare; we report a unique case of simultaneous presentation in a patient with mild anaemia and jaundice, a rare occurrence documented only once in literature. This rare combination of conditions, characterized by overlapping symptoms and diagnostic complexities, highlights the need for an all-encompassing approach to ensure accurate diagnosis and effective management. Multidisciplinary collaboration and laboratory investigations including genetic testing for Gilbert's syndrome played a pivotal role in providing appropriate care in our case. Effective communication between laboratory professionals and medical consultants is of paramount importance in achieving precise diagnoses and optimal patient care.

In underdeveloped nations like India, rheumatic heart disease (RHD) is a serious public health concern that significantly increases cardiac morbidity and mortality. It is a progressive form of heart valves damage that leads to dysfunction of the heart. According to WHO 2020, It is urgently necessary to clarify the pathogenic mechanisms underlying RHD in order to develop therapeutic interventions. Molecular mimicry (MM), the fundamental mechanism underlying RHD, is triggered by antigens on group A streptococcus (GAS) to activate CD4 + T cells, which subsequently cross-react with related peptides in the tissue surrounding the heart valve. Although, the most well-established theory for the development of RHD is MM, however, over the past few years, competence of MM theory to elucidate autoimmune diseases in RHD is questioned several times. The GAS first adheres and colonize on the surface of epithelium of the heart and then with the help of various adhesion molecules invade the heart valves and cause inflammation. Furthermore, the observation that multiple members of the affected person's family have RHD supports the idea that genetics plays a role in the RHD pathogenesis. This suggests a genetic predisposition for RHD. Therefore, in the present review, besides MM, other factors such as cellular proteins, various cells producing cytokines and chemokines, and genetic factors that leads to disease manifestation have been discussed.

[This corrects the article DOI: 10.1007/s12291-024-01212-0.].

Colorectal cancer (CRC) manifests as a prevalent malignancy marked by distinct gene expression patterns. In the intricate landscape of cancer development, non-coding RNAs, particularly long non-coding RNAs (lncRNAs), exert a substantial influence. This research aimed to investigate the expression patterns of the antisense long non-coding RNA (lncRNA), LENG8-AS1, and its consequential impact on the survival outcomes of patients diagnosed with CRC. Utilizing TCGA data and the TCGA Biolinks packages, a comprehensive analysis was conducted to identify potential lncRNA candidates implicated in CRC. The clinical data underwent Cox regression analysis to evaluate the correlation between the expression levels of selected lncRNAs, including LENG8-AS1, and the survival rates of patients. The predictive model of survival rates was visually represented through Kaplan-Meier plots. To validate the findings, real-time quantitative polymerase chain reaction (RT-qPCR) was performed on CRC samples and adjacent normal tissues. Data revealed that several lncRNAs, including CAPN10-AS1 and LENG8-AS1, associated with poor prognosis, while AC016027.1 and PTP4A1-AS1 were linked to better prognosis. Kaplan-Meier analysis supported the potential of these lncRNAs as prognostic markers for CRC. LENG8-AS1, a less-studied lncRNA in CRC, was found to be upregulated and was correlated with genes involved in lipid metabolism and angiogenesis pathways. RT-qPCR confirmed the increased expression of LENG8-AS1 in CRC samples. Additionally, ROC curve analysis demonstrated the potential of LENG8-AS1 as a valuable biomarker for CRC. Overall, these findings suggest that LENG8-AS1 may serve as a biomarker for CRC, with its increased expression being associated with tumor progression and poor patient prognosis.

This review focuses on the roles of the two primary sulfur-containing amino acids, cysteine and methionine, in regulating reactive oxygen/nitrogen species (RONS). RONS are highly reactive oxygen/nitrogen-containing free radicals and compounds. Endogenous and exogenous antioxidants, including sulfur-containing amino acids, protect cells against the harmful effects of RONS on cellular macromolecules. This study thoroughly reviews the mechanisms by which these two sulfur-containing amino acids neutralize RONS. Additionally, a bioinformatic analysis of the percentage compositions of cysteine and methionine in metabolic proteins of humans and 12 closely related species was conducted using a "Biopython" script to assess their potential role as sinks for RONS, maintaining the structure and function of metabolic proteins. A total of 119 proteins from various metabolic pathways, including glycolysis, pyruvate to acetyl CoA conversion, tricarboxylic acid cycle, oxidative phosphorylation, pentose phosphate pathway, gluconeogenesis, glycogen metabolism, fatty acid metabolism, amino acid catabolism, nucleotide biosynthesis, and ROS scavengers were included in the bioinformatics analysis. This review shows that methionine and cysteine play crucial roles in neutralizing RONS. The bioinformatic analysis revealed that the percentage compositions of methionine and cysteine are higher in key redox enzymes like dehydrogenases, enzymes involved in oxidative phosphorylation, and those participating in the committed steps of metabolic pathways.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01284-y.