Searches / Indian Journal Of Clinical Biochemistry[JOURNAL]

Indian Journal Of Clinical Biochemistry[JOURNAL]

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Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development.

Ay A, Alkanli N, Cevik G

Indian J Clin Biochem · 2024 Jan · PMID 38223012 · Full text

The aim of this study is to determine the roles of eNOS gene variations in BCA development. Our study included 91 patients diagnosed with BCA and 91 healthy controls. eNOS 4VNTR (4a/b), T786C and G894T gene variations ge... The aim of this study is to determine the roles of eNOS gene variations in BCA development. Our study included 91 patients diagnosed with BCA and 91 healthy controls. eNOS 4VNTR (4a/b), T786C and G894T gene variations genotype distributions were determined by PCR and RFLP methods. The significant difference was determined between these groups in terms of eNOS T786C and eNOS G894T gene variations genotype distributions ( < 0.05). TT genotype for G894T gene variation and CC genotype for T786C gene variation were detected higher in patients. The CC genotype of T786C gene variation was detected significantly higher in male patients than in male controls ( < 0.05). In addition, aa-TT, ab-TT, bb-TT haplotypes of 4VNTR (4a/b)-G894T gene variations, aa-CC, ab-CC, bb-CC haplotypes of 4VNTR (4a/b)-T786C gene variations and TT-TT, TT-CC, TT-CT, GG-CC, GT-CC haplotypes of G894T-T786C gene variations were observed in patient group more than control group. The significant difference was detected between these groups in terms of eNOS (G894T-T786C) haplotypes ( < 0.05). In our study, eNOS T786C and eNOS G894T gene variations were determined important genetic risk factor in the Thrace population of Turkey.

Protein Carbonyl, Lipid Peroxidation, Glutathione and Enzymatic Antioxidant Status in Male Wistar Brain Sub-regions After Dietary Copper Deficiency.

Kurup AR, Nair N

Indian J Clin Biochem · 2024 Jan · PMID 38223011 · Full text

Copper a quintessential transitional metal is required for development and function of normal brain and its deficiency has been associated with impairments in brain function. The present study investigates the effects of... Copper a quintessential transitional metal is required for development and function of normal brain and its deficiency has been associated with impairments in brain function. The present study investigates the effects of dietary copper deficiency on brain sub-regions of male Wistar rats for 2-, 4- and 6-week. Pre-pubertal rats were divided into four groups: negative control (NC), copper control (CC), pairfed (PF) and copper deficient (CD). In brain sub regions total protein concentration, glutathione concentration and Cu-Zn SOD activity were down regulated after 2-, 4- and 6 weeks compared to controls and PF groups. Significant increase in brain sub regions was observed in protein carbonyl and lipid peroxidation concentration as well as total SOD, Mn SOD and catalase activities after 2-, 4- and 6 weeks of dietary copper deficiency. Experimental evidences indicate that impaired copper homeostasis has the potential to generate reactive oxygen species enhancing the susceptibility to oxidative stress by inducing up- and down-regulation of non-enzymatic and enzymatic profile studied in brain sub regions causing loss of their normal function which can consequently lead to deterioration of cell structure and death if copper deficiency is prolonged.

A Novel Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation.

Kumar P, Paramasivam G, Devasia T … +8 more , Prabhu M, Rai MK, Prakashini K, Mallya S, Reghunathan D, Megha A, Nayak K, Moka R

Indian J Clin Biochem · 2024 Jan · PMID 38223010 · Full text

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterised by unexplained left ventricular hypertrophy in the absence of abnormal loading conditions. The global prevalence of HCM is estimated... Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterised by unexplained left ventricular hypertrophy in the absence of abnormal loading conditions. The global prevalence of HCM is estimated to be 1 in 250 in the general population. It is caused due to mutations in genes coding for sarcomeric proteins. α-tropomyosin is an important protein in the sarcomeric thin filament which regulates sarcomere contraction. Mutations in are known to cause hypertrophic cardiomyopathy, dilated cardiomyopathy and left ventricular non-compaction. Mutations in causing hypertrophic cardiomyopathy are < 1%. However, some high-risk mutations causing sudden cardiac death are also known in this gene. We present a case of a novel heterozygous mutation, NM_001018005.2:c.203A>G, p.Gln68Arg; co-segregating in an Indian family with hypertrophic cardiomyopathy. Our report expands the mutational spectrum of HCM due to and provides the correlated cardiac phenotype.

Monosodium Glutamate Even at Low Dose May Affect Oxidative Stress, Inflammation and Neurodegeneration in Rats.

Kesherwani R, Bhoumik S, Kumar R … +1 more , Rizvi SI

Indian J Clin Biochem · 2024 Jan · PMID 38223009 · Full text

Monosodium glutamate (MSG) is a widely used flavour enhancer. A daily intake of MSG at high dosage (2000-4000 mg/kg body weight) is reported to be toxic to humans and experimental animals. The present study aims to inves... Monosodium glutamate (MSG) is a widely used flavour enhancer. A daily intake of MSG at high dosage (2000-4000 mg/kg body weight) is reported to be toxic to humans and experimental animals. The present study aims to investigate the toxic effect of oral administration of MSG at low concentrations (30 and 100 mg/kg body weight) by evaluating biochemical parameters of oxidative stress and inflammation in blood; expression of neuroinflammatory gene and histopathological changes in brain on male Wistar rats. The administration of MSG significantly increases serum level of fasting glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein and decrease level of high-density lipoprotein. Significant low level of FRAP, GSH, SOD, CAT and higher level of MDA, PCO, AOPP, PMRS, NO, CRP, IL-6, TNF-α confirms substantial oxidative stress followed by inflammation after 100 mg MSG treatment. RT-PCR figure shows significant expression of neuroinflammatory gene IL-6 and TNF-α and histopathological examination revealed severe neurodegeneration in hippocampus (CA1 and CA3) and cerebral cortex region of brain at 100 mg MSG treatment. Our result provides evidence that MSG administration at 30 mg does not impose toxicity, however at 100 mg/kg body weight, which is considered a low dose, there is significant toxic effects and may be detrimental to health.

Irisin and Triglyceride Glucose Index as Markers of Dyslipidemia in Young Adults.

Nilofer Sagana MK, Arul Senghor KA, Vinodhini VM … +1 more , P R

Indian J Clin Biochem · 2024 Jan · PMID 38223008 · Full text

Irisin, is a new myokine, considered a favorable metabolic factor and inversely associated with non-communicable diseases. The biological activities of irisin are currently unknown; however, they include browning white a... Irisin, is a new myokine, considered a favorable metabolic factor and inversely associated with non-communicable diseases. The biological activities of irisin are currently unknown; however, they include browning white adipose tissue, insulin sensitivity, and anti-inflammatory and antioxidant effects. Triglyceride glucose index is a notable insulin resistance marker that predicts the risk of metabolic dyslipidemia and cardiovascular risk. The study aimed to evaluate the relation of irisin and Triglyceride glucose index (TyG) in young adults to assess the cardiovascular risk. This observational cross-sectional study included 80 participants aged 18 to 35 years (male and females) with cut-off TyG > 4.5 as the prime criteria. With consent, anthropometric measurements were documented. Fasting lipid profile parameters were analyzed, and atherogenic lipid ratios and TyG index were calculated. Serum irisin was analyzed in Bio-Rad ELISA using a standardized Abbkine kit. Decreased irisin levels (0.32 ± 0.04ng/ml) and increased TyG index (4.95 ± 0.012) were observed in the participants with elevated triglyceride levels. The lipid profile parameters and atherogenic lipid ratios were observed to be elevated in males as compared to females. Correlation of irisin with lipid parameters revealed statistically significant positive correlation with HDLc (r = + 0.305) and negative correlation with non-HDLc (r = - 0.393), TC/HDLc (r = -0.508), LDLc/HDLc (r= -0.475) and TyG (r = -0.28). The study concludes that decreased irisin and increased TyG index in young adults reflect the state of metabolic dyslipidemia which enables the identification of individuals with metabolic and atherogenic risk.

Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics.

Nisa KU, Tarfeen N, Mir SA … +3 more , Waza AA, Ahmad MB, Ganai BA

Indian J Clin Biochem · 2024 Jan · PMID 38223007 · Full text

Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in na... Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.

An Updated Trial Sequential Meta-analysis of Vitamin D Receptor Gene Polymorphism (Fok1, Bsm1, Taq1 and Apa1) and Risk to Tuberculosis.

Shah S, Priyanka, Sharma S

Indian J Clin Biochem · 2024 Jan · PMID 38223006 · Full text

UNLABELLED: Vitamin D receptor (VDR) is one of the most widely studied genes for the Tuberculosis (TB) susceptibility. Several studies have been conducted to establish some association between them but most of the time t... UNLABELLED: Vitamin D receptor (VDR) is one of the most widely studied genes for the Tuberculosis (TB) susceptibility. Several studies have been conducted to establish some association between them but most of the time they are contradictory and underpowered. So, a trial sequential meta-analysis between VDR gene polymorphisms and TB susceptibility can provide a better understanding of the relationship. A meta-analysis was carried out using a total of 17 case-control studies which includes Fok1 (14 Studies), Bsm1 (8 Studies), Apa1 (8 Studies) and Taq1 (12 Studies) polymorphisms in the VDR gene searched from Pubmed and Google Scholar. Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were calculated using StatsDirect Version 3, using random effects model. Trial sequential analysis (TSA) was also performed to assess if the statistical significance of the meta-analysis was within monitoring boundaries. It was found that the individuals with BB genotype of Bsm1 polymorphism with OR = 0.713 (95%CI = 0.521, 0.974; p value < 0.05) and FF genotype of Fok1 polymorphism with pooled OR = 0.716 (95%CI = 0.523, 0.979; p value < 0.05) had decreased incidence of TB. Also, the aa genotype of Apa1 gene polymorphism increases susceptibility to TB with pooled OR = 1.997 (95%CI = 1.121, 3.558; p value < 0.05). All these analyses reached the required information size through TSA analysis. No statistically significant result was found for Taq1 polymorphisms and TB susceptibility. VDR polymorphisms in Fok1 and Bsm1 played protective roles against development of TB infection, while Apa1 appeared to have a significant association to TB susceptibility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01091-3.

Diabetic Encephalopathy: Role of Oxidative and Nitrosative Factors in Type 2 Diabetes.

Mazumdar D, Singh S

Indian J Clin Biochem · 2024 Jan · PMID 38223005 · Full text

Diabetes mellitus is a set of complex metabolic disorders characterized by chronic hyperglycaemic condition due to defective insulin secretion (Type 1) and action (Type 2), which leads to serious micro and macro-vascular... Diabetes mellitus is a set of complex metabolic disorders characterized by chronic hyperglycaemic condition due to defective insulin secretion (Type 1) and action (Type 2), which leads to serious micro and macro-vascular damage, inflammation, oxidative and nitrosative stress and a deranged energy homeostasis due to imbalance in the glucose and lipid metabolism. Moreover, patient with diabetes mellitus often showed the nervous system disorders known as diabetic encephalopathy. The precise pathological mechanism of diabetic encephalopathy by which it effects the central nervous system directly or indirectly causing the cognitive and motor impairment, is not completely understood. However, it has been speculated that like other extracerebellar tissues, oxidative and nitrosative stress may play significant role in the pathogenesis of diabetic encephalopathy. Therefore, the present review aimed to explain the possible association of the oxidative and nitrosative stress caused by the chronic hyperglycaemic condition with the central nervous system complications of the type 2 diabetes mellitus induced diabetic encephalopathy.

The 'Insertion/Deletion' Polymorphism, rs4340 and Diabetes Risk: A Pilot Study from a Hospital Cohort.

Shah M, Gupta A, Talekar M … +5 more , Chaaithanya K, Doctor P, Fernandes S, Doctor R, Marita AR

Indian J Clin Biochem · 2024 Jan · PMID 38223004 · Full text

The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian... The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes. Genomic DNA, isolated from a cohort of 410 urban subjects attending our hospital, was genotyped using polymerase chain reaction followed by electrophoresis. Among the subjects, 84 had type-2 diabetes and 68 had hypertension while 258 were free from these risk factors. Majority (57/84) of diabetic subjects were also suffering from hypertension. Genotype frequencies of ACE I/D polymorphism, of diabetic (84) patients were not different from that of non-diabetic subjects (258). In sharp contrast, we found significant differences, in genotype frequencies of women with diabetes (n = 38) compared to non-diabetic women (70). Diabetic women had significantly higher prevalence of the high risk 'D' allele. Analysis of odds ratio, OR revealed that women with 'D/D' genotype, exhibited threefold risk (OR 3.12, 95% CI 1.21-8.05; p = 0.018) of diabetes, in the recessive model (D/D vs I/I + I/D). Further when we analysed Odds ratio of diabetic women (8) who were free from hypertension, the results revealed even a greater, 6- fold (OR 6.0, 95% CI 1.29-27.96, p = 0.027) risk of diabetes for D/D homozygous women (D/D vs I/I + I/D). These results suggest 'sex-specific' association of ACE 'I/D' polymorphism, with type-2 diabetes, affecting women while there was no influence observed among men. In view of the increased cardiovascular mortality among Indians, data from our pilot study if confirmed in a larger cohort, could add value to our future intervention efforts.

Evaluation of Bone Turnover Markers Such as Osteoprotegerin, Sclerostin and Dickkopf-1 in Subclinical Hyperthyroidism.

Özbek AE, Korkmaz H, Sözen M … +5 more , İpekçi SH, Abuşoğlu S, Kıraç CO, Ünlü A, Kebapçılar L

Indian J Clin Biochem · 2024 Jan · PMID 38223003 · Full text

In this study, it was aimed to assess effects of subclinical hyperthyroidism (SH) on bone metabolism using osteoprotegerin (OPG), sclerostin, Dickkopf-1 (DKK1) and biochemical parameters. This cross-sectional prospective... In this study, it was aimed to assess effects of subclinical hyperthyroidism (SH) on bone metabolism using osteoprotegerin (OPG), sclerostin, Dickkopf-1 (DKK1) and biochemical parameters. This cross-sectional prospective study included 40 patients with SH and 40 euthyroid controls. Serum OPG, sclerostin, DKK-1, type-1 procollagen, C-terminal polypeptide (CTx) and 24-hours urine N-terminal telopeptide (NTx) were measures using ELISA kit. Bone mineral density measurements were performed using dual energy X-ray absorptiometry (DEXA). Risk for 10-years hip and major fracture was estimated by Turkish version of FRAX. No significant difference was detected in age, gender, body mass index, smoking and menopause rates between SH and control groups. The risk for 10-years hip fracture and major osteoporotic fracture were estimated as 4.45% and 0.55% in SH group, respectively. The OPG levels were significantly lower in patients with SH than controls ( = 0.017). No significant difference was detected in other bone formation and degradation parameters. No significant correlation was detected between OPG level and risk for major osteoporotic fracture ( > 0.05); however, a negative correlation was detected between OPG level and risk for hip fracture (rho = 0.233;  = 0.038). Serum OPG is markedly affected in patients with SH. In addition, OPG seemed to be associated with osteoporotic fracture risk. Available data show that SH is significantly associated with risk for fracture; thus, it is important to assess risk for fracture in patients with SH.

Role of Supply Chain Management in Clinical Laboratory.

Mitra P, Gupta S, Sharma P

Indian J Clin Biochem · 2024 Jan · PMID 38223002 · Full text

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Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis.

Namiduru ES, Namiduru M, Karaoğlan İ … +1 more , Erbağci E

Indian J Clin Biochem · 2024 Jan · PMID 38223001 · Full text

Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role... Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role and efficacy of serum and cerebrospinal fluid heparin binding protein in differentiating bacterial meningitis from tuberculosis and viral meningitis. A case diagnosed with acute bacterial meningitis (n:37), viral meningitis (n:30) and tuberculous meningitis (n:30) was included in this study. The diagnosis was based on history, clinical criteria, cerebrospinal fluid examination, latex agglutination and culture, and response to therapy. Heparin-binding protein was measured using enzyme-linked immunosorbent technique in both cerebrospinal fluid and serum. Cerebrospinal fluid heparin-binding protein levels were 7.81 ± 0.23 ng/mL in bacterial meningitis, 6.11 ± 0.3 ng/mL in tuberculosis meningitis and 5.75 ± 0.1 ng/mL in viral meningitis. The mean serum level was 14.98 ± 1.1 ng/mL in bacterial meningitis, 6.89 ± 0.4 ng/mL in tuberculosis meningitis, and 6.02 ± 0.4 ng/mL in viral meningitis. Both heparin-binding protein levels were significantly higher in patients with bacterial meningitis. We found that serum and cerebrospinal fluid heparin binding protein is a useful marker for differentiating bacterial meningitis from non-bacterial meningitis.

Homeodomain Transcription Factors Nkx2.2 and Pax6 as Novel Biomarkers for Meningioma Tumor Treatment.

Farheen S, Pm MM, Rehman S … +5 more , Hoda MF, Gupta Y, Ali A, Chosdol K, Shahi MH

Indian J Clin Biochem · 2024 Jan · PMID 38223000 · Full text

UNLABELLED: Meningioma is a common brain tumour which has neither a specific detection nor treatment method. The Sonic hedgehog (Shh) cell signaling pathway is a crucial regulatory pathway of mammalian organogenesis and... UNLABELLED: Meningioma is a common brain tumour which has neither a specific detection nor treatment method. The Sonic hedgehog (Shh) cell signaling pathway is a crucial regulatory pathway of mammalian organogenesis and tumorigenesis including meningioma. Shh cell signalling pathway cascade function by main transcription factor Gli1 and which further regulates in its downstream to Pax6 and Nkx2.2. This current study is aimed to explore the regulation of the Sonic hedgehog-Gli1 cell signaling pathway and its potential downstream targets in meningioma samples. A total of 24 surgically resected meningioma samples were used in this current study.Cytological changes were assessed using electron microscopic techniques as well as hematoxylin & eosin and DAPI staining. The expression pattern of Gli1, Nkx2.2 and Pax6 transcription factors were determined by using immunohistochemistry. The mRNA expression was assessed using RT-qPCR assays. Later, the whole transcriptome analysis of samples was performed with the amploseq technique. Results were compared with those obtained in normal human brain tissue (or normal meninges). Compared to the normal human brain tissue, meningioma samples showed crowded nuclei with morphological changes. Transcription factor Nkx2.2 expressed highly in all samples (24/24, 100%). Twenty-one of the 24 meningiomas (88%) showed high Gli1 and Pax6 expression. Whole transcriptome analysis of two meningioma samples also exhibited a very high increase in Gli1 expression signal in meningioma samples as compare to normal control. Hence, we may conclude that the Shh-Gli1 pathway is aberrantly activated in meningioma cells and is canonically upregulating the expression of transcription factors Pax6 and Nkx2.2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01085-1.

Vitamin C Improves Inflammatory-related Redox Status in Hyperlipidemic Rats.

Kumar R, Rizvi SI

Indian J Clin Biochem · 2023 Oct · PMID 37746546 · Full text

Excessive dietary fat is mainly responsible for metabolic diseases including atherosclerosis and cardiovascular disease. We have evaluated the role of Vitamin C in an experimental hyperlipidemic model of rats (male Wista... Excessive dietary fat is mainly responsible for metabolic diseases including atherosclerosis and cardiovascular disease. We have evaluated the role of Vitamin C in an experimental hyperlipidemic model of rats (male Wistar rat 12-16 months). The hyperlipidemic model of the rat was created by treatment with an atherogenic suspension: cholesterol, cholic acid, and coconut oil, for 30 days once daily, and supplemented with Vitamin C (Ascorbic acid) doses of 0.5 g/kg body weight (orally) for the 30 days once daily. Bodyweight, fasting glucose, triglyceride, cholesterol, ROS (Reactive oxygen species), MDA (Malondialdehyde), FRAP (Ferric reducing the ability of plasma), GSH (Reduced glutathione), PCO (Protein carbonyl), PON-1(Paraoxonase-1), AGE (Advanced glycation end product), PMRS (Plasma membrane reduced system), and inflammatory cytokines (TNF-α and IL-6) were estimated in blood and plasma. Our result shows that oxidative stress, and inflammatory markers, were increased in the HFD-treated group of rats. Vitamin C supplementation protected against lipidemic and, oxidative stress. We conclude that Vitamin C may be useful in maintaining cellular redox balance and protecting against lipidemic stress.

Association of the Human Leptin Receptor Gene (rs1137101; Gln223Arg) Polymorphism and Circulating Leptin in Patients with Metabolic Syndrome in the Indian Population.

Parchwani D, Dholariya S, Patel DD … +6 more , Agravatt A, Uperia J, Parchwani T, Singh R, Radadiya M, Desai Y

Indian J Clin Biochem · 2023 Oct · PMID 37746545 · Full text

Phenotypic expression of metabolic syndrome is precipitated by environmental variables along with the individual genetic susceptibility to the obesogenic environment and growing body of evidence suggest a paramount role... Phenotypic expression of metabolic syndrome is precipitated by environmental variables along with the individual genetic susceptibility to the obesogenic environment and growing body of evidence suggest a paramount role of adipocytokines. Therefore, identifying the genetic influence on circulation leptin levels and clarifying genotype-phenotype correlation of rs1137101 {Leptin receptor gene (LEPR) Gln223Arg (Q223R; A668G)} in metabolic syndrome were the primary objective of this study. A total of 447 adult participants, including 214 metabolic syndrome patients and 233 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci {Leptin receptor gene; Gln223Arg (Q223R; A668G); rs1137101} on the occurrence of metabolic syndrome in consort with circulation leptin levels. Suitable descriptive statistics was used for different variables. The genotype frequencies were found to be in Hardy-Weinberg equilibrium for both cases (p > 0.2722) as well as in controls (p > 0.2331). However, genotype (x2: 11.26, 2 d.f. p = 0.0036) and allele distribution (x2: 10.51, 2 d.f. p: 0.0012) of the LEPR Gln223Arg (Q223R; A668G) differed significantly between cases and controls. Gln/Arg genotype (OR = 1.6099; 95% CI = 1.0847-2.3893; p value = 0.0181), Arg/Arg genotype (OR = 2.8121; 95% CI = 1.4103-5.6074; p value = 0.0033) and R allele (OR = 1.5875; 95% CI = 1.1996-2.1008; p value = 0.0012) were significantly associated with increased risk of metabolic syndrome in univariate analysis. Further a multivariate logistic regression adjusted for potential confounders showed that Arg/Arg genotype (OR = 1.9; 95% CI = 1.271-2.639; p-value < 0.05) and Gln/Arg (OR: 1.3; 95% CI = 0.873-2.034; p value < 0.05) have a significant risk for the occurrence of the metabolic syndrome. A progressive increase in the serum leptin levels from major homozygous alleles to minor homozygous alleles were observed indicating that rs1137101 modify the serum leptin concentrations in patients with metabolic syndrome. These findings provide enough evidence of a significant association of LEPR Gln223Arg (Q223R; A668G) polymorphism in the LepR gene in Indian patients with increased risk of metabolic syndrome for R allele and Arg/Arg homozygote. Thus, rs1137101 might be a pleiotropic locus for metabolic syndrome and its components in studied population.

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity.

Zare N, Dana N, Mosayebi A … +2 more , Vaseghi G, Javanmard SH

Indian J Clin Biochem · 2023 Oct · PMID 37746544 · Full text

UNLABELLED: The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could pred... UNLABELLED: The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2 values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group ( = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

Association of Serum Complement C3 Levels with Severity and Mortality in COVID 19.

Tomo S, Kiran Kumar P, Yadav D … +11 more , Sankanagoudar S, Charan J, Purohit A, Nag VL, Bhatia PK, Singh K, Dutt N, Garg MK, Misra S, Sharma P, Purohit P

Indian J Clin Biochem · 2023 Oct · PMID 37746543 · Full text

UNLABELLED: The severe acute respiratory distress syndrome-associated coronavirus-2 infection can activate innate and adaptive immune responses which may lead to harmful tissue damage, both locally and systemically. C3,... UNLABELLED: The severe acute respiratory distress syndrome-associated coronavirus-2 infection can activate innate and adaptive immune responses which may lead to harmful tissue damage, both locally and systemically. C3, a member of complement system of serum proteins, is a major component of innate immune and inflammatory responses. This study is aimed to assess serum C3 as a marker of COVID-19 severity and a predictor of disease progression. A total of 150 COVID-19 patients, confirmed by RT-PCR, and 50 healthy controls were recruited. Serum C3 levels were determined by using direct colorimetric method. Median levels of serum C3 in total cases and controls were 157.8 and 165.7 mg/dL respectively. Serum C3 although not significantly decreased, they were lower in cases when compared to controls. Similarly, significant differences were found between the groups, with severe group (140.6 mg/dL) having low levels of serum C3 protein when compared to mild (161.0 mg/dL) and moderate group (167.1 mg/dL). Interestingly, during hospitalization, significant difference between baseline (admission) and follow-up (discharge) was observed only in patients with moderate disease. Based on our results, lower levels of C3, with an increase in IL-6 and d-dimer levels, are associated with higher odds of mortality. Therefore, we would like to emphasize that measuring serum C3 levels along with other inflammatory markers might give an added advantage in early identification of patients who are prone to having a severe disease course and can help in a more effective follow-up of disease progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01148-x.

Acton-Prolongatum Stimulated Blood Steroid Profile in Apparently Healthy Asian Indian Women of Reproductive-Age Group.

Sarathi V, Reddy A, Tirupati S … +1 more , Jumkhawala K

Indian J Clin Biochem · 2023 Oct · PMID 37746542 · Full text

Blood steroid profile is a recently introduced test in India that is commercially available through a few diagnostic laboratories. In adult women, ACTH-stimulated steroid panel helps to differentiate polycystic ovary syn... Blood steroid profile is a recently introduced test in India that is commercially available through a few diagnostic laboratories. In adult women, ACTH-stimulated steroid panel helps to differentiate polycystic ovary syndrome (PCOS) from nonclassical forms of CAH. However, the interpretation of ACTH-stimulated steroid panels is often impeded by the limited availability of reference ranges. Here, we report the adrenal steroid levels after stimulation with Acton Prolongatum in Asian Indian women of reproductive age. This prospective study was conducted at a tertiary health care center in the Southern part of India. Apparently healthy women in the reproductive age group with regular menstrual cycles (21-35 days) at least over the last 6 months were included. All participants received intramuscular Acton Prolongatum® (Pfizer) in the morning hours during the follicular phase and the steroid profile was analyzed by liquid chromatography-tandem mass spectrometry in a blood sample collected 60-min later. The study included 32 apparently healthy women. The mean age of the study population was 22.19 ± 4.36 years. None of the participants experienced any adverse events during the procedure. The median (range) serum cortisol, 17α-hydroxyprogesterone, 11-deoxycortisol, and corticosterone were 22.65 (14.3-37.21) μg/dl, 99.72 (47.21-344.71) ng/dl, 287.2 (74.41-530.61) ng/dl and 728.04 (118.74-1708.2) respectively. In conclusion, this is the first report of the response of adrenal steroids measured by LC-MS/MS at 60 min after Acton Prolongatum in Asian Indian women of the reproductive age group. However, further larger studies are warranted to establish more robust ACTH-stimulated reference ranges for steroid profile in Indian women.

Metabolic and Genetic Association of Vitamin D with Calcium Signaling and Insulin Resistance.

Tarfeen N, Nisa KU, Ahmad MB … +2 more , Waza AA, Ganai BA

Indian J Clin Biochem · 2023 Oct · PMID 37746541 · Full text

Various evidences have unveiled the significance of Vitamin D in diverse processes which include its action in prevention of immune dysfunction, cancer and cardiometabolic disorders. Studies have confirmed the function o... Various evidences have unveiled the significance of Vitamin D in diverse processes which include its action in prevention of immune dysfunction, cancer and cardiometabolic disorders. Studies have confirmed the function of VD in controlling the expression of approximately nine hundred genes including gene expression of insulin. VD insufficiency may be linked with the pathogenesis of diseases that are associated with insulin resistance (IR) including diabetes as well as obesity. Thus, VD lowers IR-related disorders such as inflammation and oxidative stress. This review provides an insight regarding the molecular mechanism manifesting, how insufficiency of VD may be connected with the IR and diabetes. It also discusses the effect of VD in maintaining the Ca levels in beta cells of the pancreas and in the tissues that are responsive to insulin.

In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles.

Kaur B, Kaur M, Ahlawat P … +1 more , Sharma S

Indian J Clin Biochem · 2023 Oct · PMID 37746540 · Full text

UNLABELLED: Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, com... UNLABELLED: Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01062-8.
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