Indian Journal of Clinical Biochemistry最新文献

Tyrosinemia type I is a rare autosomal recessive metabolic disease caused by the deficiency of Fumarylacetoacetate hydrolase (FAH). The deficiency leads to the accumulation of toxic metabolites leading to the hepatorenal complications. The present study was planned for the identification of the spectrum of disease-causing mutations in the FAH gene of North Indian population. 70 clinically suspected tyrosinemia type I patients were recruited. Urinary Succinylacetone was estimated using Gas Chromatography Mass spectrometry (GCMS). The gene FAH was sequenced by Sanger sequencing in the patients whose exons showed band mobility change by single standard conformation polymorphism (SSCP) screening. Identified variants were functionally analyzed using insilico software tools for identification of pathogenic variants with in vitro functional characterization. Urinary Succinylacetone was not detected in urine of the recruited patients. Sequencing analysis revealed 24variants in nine patients. The majority of these variants were predicted to be disease causing by in silico software programs. In vitro, analysis showed that variants L17P + F22I + I373T and G307X, S130C and G307X can reduce protein expression and catalytic activity of FAH. Tyrosinemia type I is a rare disease but has severe mortality and morbidity. In India, diagnostic and treatment strategies are insufficient against this disease; therefore, majority of the cases may remain undiagnosed. Identification of these disease-causing mutations in the recruited study subjects implicate the requirement of neonatal or prenatal screening for Tyrosinemia Type I in future.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01236-6.

An ideal level of vital trace elements (TE) is crucial for the immune system to protect organs from infections. TE, in particular, zinc (Zn), copper (Cu), magnesium (Mg), manganese (Mn), chromium (Cr), and iron (Fe), affect an individual's sensitivity to the exposure and progression of viral diseases, such as COVID-19. Therefore, this study evaluated the level of these TE during hospitalization in an isolation center and investigated their association with the severity of COVID-19. This study included 118 individuals, 63 male and 55 female aged between 20 and 60 years. Seventy-eight COVID-19 patients and 40 healthy individuals were included in this study. Infected individuals were classified into moderate and severe based on the severity of their symptoms. The levels of Zn, Mg, Mn, Cr, and Fe were significantly decreased in moderate and severe groups compared to the controls (p < 0.0001), respectively. Conversely, levels of Cu were found significantly increasing compared to individuals in the control's groups (p < 0.0001). Among the total number of infected cases, the levels of Zn, Cu, Mn, Cr, and Fe did not significantly increase with increasing severity (from moderate to severe). The findings indicated that TE levels were not altered in a severity-dependent manner, showing that TE affect the individual's vulnerability to COVID-19, not its progression.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01254-4.

Toxic metal exposure is a global health concern with serious implications for human well-being. Metals such as lead, mercury, arsenic, and cadmium are widely present in the environment due to natural processes and human activities, including industrial emissions, mining, and agricultural practices. Humans are exposed to these metals through inhalation, ingestion, and dermal contact via contaminated air, water, food, and consumer products. Once inside the body, toxic metals disrupt cellular functions by inducing oxidative stress, interfering with enzymatic activity, and binding to biomolecules like proteins and DNA. This leads to cellular damage, inflammation, and apoptosis. The health consequences are severe, affecting multiple organ systems. Lead and mercury are known for their neurotoxic effects, leading to cognitive impairment and neurodevelopmental deficits. Cadmium exposure is linked to hypertension and cardiovascular disease, while arsenic and cadmium have carcinogenic properties, increasing the risk of lung, bladder, and liver cancer. Kidney damage is another major concern associated with cadmium and lead exposure. Preventing toxic metal exposure requires stringent regulations, pollution control measures, and public education. Environmental monitoring and biomarker assessments are essential for identifying at-risk populations. Effective strategies include reducing industrial emissions, promoting safer alternatives, and implementing global policies to minimize contamination. Addressing toxic metal exposure requires a collaborative effort at local, national, and international levels to safeguard public health and mitigate long-term health risks.

The most prevalent inflammatory arthropathy in the world is rheumatoid arthritis (RA). An essential part of the pathogenesis of RA involves autoimmune responses. Variants in lncRNAs may have an impact on the course and/or result of a disease and may have diagnostic or prognostic significance. Our study looked into the connection of rs12826786 and rs1899663 polymorphisms of HOX antisense RNA (HOTAIR) transcript with genetic susceptibility to RA. The study involved 300 participants in total, 150 of them were RA patients and the remaining 150 were healthy controls. Using tetra primer ARMS-PCR, the HOTAIR polymorphisms rs12826786 and rs1899663 were detected. More observations of the T allele of rs1899663 and the C allele of rs12826786 were made in the study group compared to the control group. The HOTAIR rs12826786 variant displayed a significant association with susceptibility to RA in both recessive (OR = 2.45, 95% CI = 1.47-4.09, P = 0.0004) and over-dominant (OR = 0.42, 95% CI = 0.26-0.68, P = 0.0003) models. In addition, the HOTAIR rs1899663 was shown to be linked to RA susceptibility in the co-dominant model (OR = 0.32, 95% CI = 0.17-0.61, P = 0.0004 for GG genotype), dominant model (OR = 0.48, 95% CI = 0.29-0.81, P = 0.005), and recessive model (OR = 0.43, 95% CI = 0.25-0.74, P = 0.001). The CT haplotype is linked to a greater risk of RA, whereas the CG haplotype confers protection against RA. We reported for the first time, HOTAIR rs12826786 and rs1899663 variants are associated with susceptibility to developing RA among the Iranian population. In addition, the CT and CG haplotypes were associated with the risk of RA. Further functional studies are needed to elucidate the role of these variations on HOTAIR expression.

The outbreak of the novel coronavirus disease due to the SARS-CoV-2 virus originated in Wuhan in December 2019, and emerged as a considerable global pandemic threat, with serious impact on different aspects of people's health and lives. Though, the disease is no longer considered a global emergency, its potential risks for long-term reproductive health remain a concern. Various guidelines and precautionary measures such as suspension of non-essential medical services were adopted for the containment of this deadly virus. Although such restrictions were proven to be an effective tool in preventing the spread of novel coronavirus, however, this has also negatively impacted society, including infertile couples undergoing fertility treatment. During the period of the pandemic, females experienced changes in menstrual cycles, thyroid dysfunction, and stress-associated loss in libido and other related sexual dysfunctions, leading to consequential effects on their reproductive and mental health. The SARS-CoV-2-associated defects are not only limited to female reproductive dysfunction rather the male reproductive organs were found to be equally impacted by this SARS-CoV-2 virus. The expression of ACE2 in the male reproductive count is a major factor for significant alterations observed in male reproductive function. In this current article, we have focused on the impact of SARS-CoV-2 on reproductive health, and the challenges of assisted reproductive technology (ART) during the pandemic outbreak.

The main process, for the elimination of cholesterol from the human body, involves the alteration of cholesterol into bile acid (BA), by the liver. The farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is essential for the regulation of BA, glucose, and lipid metabolism. It is largely found in the liver, intestines, kidney, and adrenal glands, and to a smaller degree in the heart and adipose tissue. The binding locations, of the FXR, are in close proximity to formerly undisclosed target genes, with distinctive activities associated with transcriptional regulators, autophagy, apoptosis, hypoxia, inflammation, RNA processing, and a number of cellular signaling pathways. The preservation of BA homeostasis, by the FXR, entails the direct stimulation of the expression of the small heterodimer partner in the liver, and the fibroblast growth factor 15/19 (FGF15/FGF19) in the intestine, which impedes the activity of enzymes associated with hepatic BA synthesis, including cytochrome P450 7A1 (Cyp7a1). This investigation delves into the role of the FXR in terms of BA metabolism regulation, as well as its role in the pathophysiologic activity of cholestasis.

Although most of the babies are born healthy and appear normal, a few babies exhibit abnormal medical conditions. Newborn screening for inborn errors of metabolism is an established panel of tests that assist in the timely recognition of treatable disorders. 8007 Neonates born in a well known hospital from August 2019 to August 2021 were screened for the following five tests: Thyroid stimulating Hormone, 17-hydroxy progesterone (17-OHP), Total Galactose(GAL), Glucose 6 Phosphate Dehydrogenase (G6PD) and Biotinidase (BTD). Dried blood spots (DBS) were processed for the above tests using Enzyme-linked immunosorbent assay (ELISA), colorimetric, and dissociation-enhanced lanthenide-fluroscent immunoassay (DELFIA) techniques. DBS with abnormal results were retested for confirmation. Affected infants were recalled for venous blood collection for confirmation. We found 4 newborns with Hypothyroidism (CH 1: 2002), 4 with congenital adrenal hyperplasia (CAH 1:2002), 9 with G6PD deficiency (1:900), one with galactose-phosphate-uridyl transferase deficiency (1: 8000) and one with biotinidase deficiencyduring the study period. Parents of G6PD deficient babies were counseled. Congenital Hypothyroidism (CH) and Congenital Adrenal Hyperplasiababies were treated and followed up to find the response. The outcome of the screening result shall prevent the family and society in turn from facing severe and unbearable consequences.