Indian Journal of Clinical Biochemistry最新文献

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.

Ellagic acid (EA) is an antioxidant and anti-inflammatory compound primarily found in pomegranates and berries. It is a dimer of gallic acid and has been shown to have health advantages. We assessed the protective effect of EA against oxidative stress caused by tert-butyl hydroperoxide (t-BHP) on erythrocyte cell membrane indicators during the aging process in humans. In control and oxidative stress caused by t-BHP in human subjects' erythrocytes of both sexes (n = 80), we evaluated the in vitro effect of EA on Na⁺, H⁺ exchanger (NHE), Na⁺, K⁺ ATPase, Ca²⁺ ATPase, protein carbonyl group content and osmotic fragility. We note that the NHE activity increases relative to their respective controls in the young, middle, and old subjects. Stress-inducing t-BHP significantly increases (p < 0.001) NHE activity in all age groups compared to the respective control. NHE activity is further reduced by EA treatment. In middle-aged and older human participants, erythrocyte membrane Na⁺, K⁺, and Ca²⁺ ATPase activity was considerably (p < 0.001) lower than in younger subjects in the control group. In all age groups, there was a noteworthy reduction (p < 0.001) in Na⁺, K⁺, and Ca²⁺ ATPase activity in the membrane of t-BHP-induced erythrocytes compared to their corresponding controls. Administration of different concentrations of EA (10^-5-10^-7 M) decreases carbonyl group content significantly compared to their respective control in each age group in a concentration-dependent manner. When the erythrocytes were induced with stress using t-BHP, the lysis % increased, and after the treatment of EA, the lysis % was found to decrease in all the age groups. The activity of membrane-bound enzymes is markedly increased when EA is applied to these erythrocyte membranes. Through the modulation of membrane transporters, the study sheds light on the beneficial health advantages of EA.

Tobacco use causes serious public health concerns and causes many health problems like (asthma, COPD, stroke, cancer, etc.). While a number of pharmacological treatments are used to reduce tobacco use, they often have adverse effects. Fewer studies have assessed non-pharmacological treatments {Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA) or fish oil} to reduce tobacco use. Omega-3 fatty acids, already known for their benefits in reducing bad cholesterol, managing diabetes, and helping with fatty liver, are now being studied for their potential impact on smoking habits. We aimed to evaluate the effect of omega-3 supplementation (flaxseed oil as a vegetarian source of alpha-linolenic acid, ALA) on tobacco craving intensity, withdrawal symptoms, and various biochemical markers in tobacco users. This single-blind, placebo-controlled study involved 104 tobacco users divided into two groups: omega-3 (n = 54) receiving 10 ml flaxseed oil daily for 6 months and placebo (n = 50). We measured tobacco craving intensity {Visual Analogue Scale (VAS)}, withdrawal symptoms {Minnesota Nicotine Withdrawal Scale (MNWS)}, demographic parameters (BMI, WHR, BP, HR), and biochemical parameters (LFT, KFT, Lipid Profile) at baseline and after 6 months. Six-month consumption of edible grade pure flaxseed oil resulted in significant lowering of BMI in omega-3 group when compared to placebo group (p = 0.0002). Also, omega-3 effectively decreased tobacco craving intensity (p < 0.0001) and its withdrawal (p < 0.0001). More intriguingly, LFT panel showed significantly lower levels of bilirubin (D) (p = 0.0216) and SGPT (p = 0.0217). Urea level (p = 0.0489) was significantly decreased while creatinine and blood urea nitrogen were comparatively decreased in omega-3 than placebo group in KFT panel. Eventually in case of lipid profile, triglycerides (p = 0.0031), LDL (p = 0.0291) and VLDL (p = 0.0055) showed significant reduction in omega-3 group. Omega-3 supplementation with flaxseed oil effectively reduces tobacco craving intensity and withdrawal symptoms, suggesting its potential for aiding tobacco cessation. Additionally, it significantly improved liver and kidney functions as well as lipid profile, highlighting its potential for broader health benefits. Trial registration This study was registered at Clinical Trial Registry-India (http://www.ctri.nic.in) with reference no. CTRI202202040681 and was performed in accordance with the Declaration of Helsinki principles.

This study delves into the exploration of exosomal transfer RNA-derived fragments (tRFs) as potential diagnostic markers for cervical cancer (CC). Employing plasma-derived exosomes isolated through ultracentrifugation and confirmed via transmission electron microscopy (TEM), qNano, and western blot analysis, we extracted total RNA from CC and adjacent tissues (n = 48), alongside exosomes from cervical cancer patients (n = 140) and healthy donors (n = 140) using Trizol reagents. The expression of exosomal tRFs was assessed through quantitative polymerase chain reaction (qPCR) and subjected to statistical analysis using Mann-Whitney U or t-tests, along with receiver operating characteristic (ROC) analysis. The findings unveiled a significant downregulation of exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 in both CC tissues and plasma samples from early-stage patients compared to healthy controls. Remarkably, these two exosomal tRFs exhibited promising capabilities as circulating biomarkers for both the diagnosis and early detection of CC, as evidenced by their high area under the curve (AUC) values of 0.9337 and 0.9432, respectively. Consequently, exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 were downregulated in CC and early-stage CC, indicating their potential as innovative non-invasive biomarkers for early CC diagnosis.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01235-7.

Hydrogen sulfide (H₂S), once recognized as a harmful gas, is now emerging as a very significant biological substance with great emphasis on neuroprotection and neuromodulation. It has several functions within the nervous system, placing its physiological activities, biochemical characteristics as well as therapeutic possibilities to their proper perspective. Endogenously produced by cystathione beta-synthase (CBS), cystathione gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) enzymes, H₂S is a unique naturally occurring substance that contains multiple biological activities; it is anti-inflammatory, antioxidant, and anti-apoptotic. Such activity allows H₂S to reduce oxidative stress, which limits mechanisms of cell death and prevents disruption of mitochondria and thus neuronal injury. H₂S can also be regarded as a neuromodulator because it interacts with and affects the glutamatergic, dopaminergic and GABAergic systems at the synaptic level as well as on neurotransmitter systems and synapse dynamics. It modulates synaptic transmission and its plasticity which is essential for cognitive as well as motor activities and exhibits anti-inflammatory effects which are helpful in the progress of the neurodegenerative condition. Recently gathered some evidence emphasizes as well the possible use of H₂S in therapeutic interventions in Alzheimer's disease, Parkinson's disease and stroke. In the models of Alzheimer's disease, H₂S is able to reduce the toxicity of amyloid-beta peptides and improve cognitive performance. In Parkinson's disease, it protects dopaminergic neurons and reduces the severity of motor deficits. Moreover, H₂S provides protection in ischemic stroke models through decrease of reactive oxygen species and inflammation. Clinical practice with H₂S-based therapies seems to have certain hurdles even if preclinical results are promising. Aside from stabilizing H₂S in a biologically active form, developing a delivery system for H₂S appears a challenge as well. This review will attempt to summarize the existing studies on H₂S as neuroprotective and neuromodulatory agents, and their avenues of future use and development.

Cancer remains one of the most pressing global health concerns, ranking as the second leading cause of death worldwide. Oxidative stress plays a pivotal role in the initiation and progression of cancer, making antioxidants a critical area of research in cancer prevention and treatment. This review aims to provide a comprehensive analysis of fruit-derived antioxidants and their potential therapeutic applications in combating cancer. In particular, it looks at how bioactive compounds like flavonoids, polyphenols, and essential vitamins found in fruits help to neutralize reactive oxygen species, control gene activity, and stop tumors from spreading and growing. The review brings together new studies from the lab, on animals, and with people that show how fruit-derived antioxidants can help fight cancer, how they change important cellular pathways, and how they might work better when combined with other treatments. Furthermore, it discusses challenges related to bioavailability, standardization, and clinical translation, underscoring the need for more robust clinical trials. This review shows how important it is to include antioxidants from fruits in dietary guidelines and move forward with targeted research into their therapeutic use in cancer management. It does this by looking at the current evidence and pointing out research gaps.

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Research has shown that endothelial dysfunction due to low nitric oxide (NO) bioavailability is one of the primary causes of preeclampsia (PE). Variations in the eNOS gene may be implicated in reducing NO levels. This study examined the relationship between eNOS gene variations and NO and malondialdehyde (MDA) levels in preeclamptic women and their neonates in Bangladesh. This study compared 100 healthy pregnant women (controls) with 82 preeclampsia-diagnosed women and their newborns. PCR-RFLP was used to detect eNOS gene variants, while spectrophotometric methods were used to measure NO and MDA levels in plasma. The maternal eNOS gene variant rs2070744 exhibited a significant relationship with PE risk, particularly under the dominant model and allele frequency scrutiny. Similarly, the neonatal eNOS gene variant rs2070744 exhibited a robust association with PE risk across various genetic models. The case‒control comparison of the genotypic distribution of NO and MDA in the studied subjects revealed that although PE mothers with TT genotypes had significantly lower NO levels than did the controls, the neonates of PE mothers with TT and CC genotypes showed a significant decrease in NO levels compared to their control groups. Moreover, the PE group and their neonates with the TT and CT genotypes had significantly greater MDA levels than did the control group. These findings illuminate the profound influence of eNOS gene variants on preeclampsia onset, suggesting a potential mechanism involving altered NO production via heightened oxidative stress among affected mothers and neonates. Consequently, screening for eNOS variants and estimating NO levels in pregnant women could offer early identification of those predisposed to PE, thus enabling timely interventions.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01264-2.

Polycystic ovary syndrome (PCOS) is the most common form of endocrinopathy of women. Several studies have investigated the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with PCOS risk but the results are contradictory. So, the aim of the present study was to carry out a meta-analysis of a published case control studies to find out exact association between MTHFR gene C677T polymorphism and PCOS susceptibility. Pubmed, Springer link, Science Direct and Google Scholar databases were searched for case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) was used as association measure and meta-analysis was performed using MIX and MetaAnalyst programs. Meta-analysis of 24 studies showed strong significant association between C677T polymorphism and PCOS risk (OR: T vs. C = 1.18, 95% CI 1.01-1.38, p = 0.03; OR: TT vs. CC = 1.37, 95% CI 1.0-1.89, p = 0.04; OR: TT + CT vs. CC = 1.31, 95% CI 1.07-1.62, p = 0.008; OR: CT vs. CC = 1.31, 95% CI 1.04-1.62, p = 0.02 and OR: TT vs. CT + CC = 1.10, 95% CI = 0.82-1.47, p = 0.04). In subgroup analysis, MTHFR C677T polymorphism is significantly associated with PCOS risk with Asian individuals but in Caucasian population MTHFR C677T polymorphism was not significantly associated with PCOS risk. In conclusion, C677T polymorphism is a risk factor for PCOS.

Cell culture techniques are the vital basis for the majority of experimental cancer research. Targeting cancer cells metabolism is one of the key strategies for controlling the growth of cancer cells. D-Mannoheptulose (MH) (as Phytotherapy) a specific inhibitor, belonging to hexokinase category, to inhibit glycolysis pathway and Doxorubicin (DXR) (as Chemotherapy) has cytotoxic activity against cancer cells and anti-cancer effects by inducing apoptosis. Evaluating the effect of D-Mannoheptulose and Doxorubicin on the normal and breast cancer cell line by determining their anti-tumor activities. Cell culture of normal human mammary epithelial cells (HMECs) and MCF-7 cell line were achieved by using Minimum Essential Medium (MEM) and RPMI-1640 Medium. D-Mannoheptulose, and Doxorubicin stock and diluted solutions were prepared by using phosphate buffer saline (PBS), and dimethyl sulphoxide (DMSO) respectively. HMECs and MCF7 cell line were treated with MH, and DXR, cytotoxicity ratio was determined by methyl thiazolyl tetrazolium (MTT). The findings of study indicated a substantial increase in the cytotoxicity and antiproliferative effects of MH and DXR depending on the concentration gradient against breast cancer cell lines and IC50 values, while on the other hand, there was no significant cytotoxic effect on normal cells. Results of the study revealed that MH, DXR, can result in inhibiting the growth of breast cancer cell lines. This behaviour was mainly due to the increase in cytotoxicity through inhibiting the glycolysis pathway thereby resulting in apoptosis. This further lead to the decrease in HK activity and hence pyruvate as well as ATP amount. Overall, DXR and MH treatment display effective cytotoxic effects against the studied breast cancer cell lines.