Indian Journal of Clinical Biochemistry最新文献

Head and neck squamous cell carcinomas (HNSCC) is one of the most prevalent type of cancer known in Indian population. Studies are needed to identify the early biomarkers for HNSCC. MicroRNAs (miRNAs) are non-coding RNA molecules, expression of which can be used as biomarker for early diagnosis of HNSCC. For miRNA profiling total RNA, which also contained small RNAs were isolated from ten HNSCC tissue samples and adjacent control. Purity and concentration of eluted RNA was assessed using the NanoDrop1000® spectrophotometer, Reverse Transcription reaction was carried out with megaplex RT primers of pool A and pool B and the expression of selected miRNAs (miR-143/145 and miR-18a/b) was measured using TaqMan primers specific for mature miRNAs. Our study showed dramatic downregulation in expression of two miRNAs, miR-18b and miR-145 in blood samples of HNSCC patients, which are inhibitor of tumorigenesis and can be targeted as biomarker of HNSCC pathogenesis therefore developing avenues for miRNA role in prognosis and therapeutics.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-023-01119-2.

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.

The development of lower respiratory complications in children with primary immunodeficiencies characterized by recurrent infections significantly contributes to morbidity and mortality. This is clinically more important and specific in the evaluation of prognosis. The inflammatory response that develops throughout the clinical process can cause the release of several biomarkers. This study aimed to evaluate the inflammatory biomarker "mid-regional pro-adrenomedullin (MR-proADM)" levels by distribution of lower respiratory tract complications. Plasma MR-proADM levels were measured in children with (n = 52) and without (n = 103) lower respiratory tract complications. The complicated group was also evaluated as "infective and non-infective" groups. The median MR-proADM levels were higher in the complicated cases (p = 0.175). It was 205.5 (73.4- 562.6) ng/L in the infective group while it was 96.1 (26.1-43.3) ng/L in the non-infective group and the difference between the two groups was statistically significant (p = 0.003). The predictive value of MR-proADM (AUC = 0.749, p = 0.003) was statistically significant compared to CRP (AUC = 0.330, p = 0.040) and SAA (AUC = 0.261, p = 0.004) in the infective group. This study evidences that the MR-proADM levels are higher in PID cases with infective pulmonary complications. Among other markers, MR-proADM appears to be a particularly good predictive inflammation marker for these children.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01061-9.

Chronic Lead (Pb) exposure is associated with disrupting certain endocrine levels and is referred to as an endocrine disruptor. Thyroid hormones, involved in regulating numerous physiological functions, are reported with conflicting associations with chronic Pb exposure. This study broadly evaluated the association between long-term lead exposure and thyroid function parameters. In this systematic review, the observational studies documenting the changes in thyroid function parameters between the chronically Pb-exposed and controls were systematically identified from PubMed-Medline, Scopus, and Embase digital databases from the beginning to March 31, 2022. The protocol was previously registered with PROSPERO (ID: CRD42022315520) and executed following PRISMA 2020 guidelines. The random-effects model was used to analyze the mean differences in thyroid function parameters between groups. The classical I² statistic was applied to assess heterogeneity, while the Newcastle Ottawa Scale was used to assess the risk of various biases. Where data allowed, sub-group, sensitivity, and meta-regression analyses were carried out. The current systematic review included fifteen observational studies. The Pb-exposed have a higher mean blood Pb level [i.e. 28.07 (95% CI 21.43-34.72) µg/dl], significantly higher free T₃ [(i.e. 0.48 pg/dl (95% CI 0.05-0.95)] and trend of higher T₃. T₄, FT₄, and TSH levels than controls with high heterogeneity (I² > 85%). Considering the important role of thyroid hormone in multiple biological functions, the present findings emphasize the requisite for high-quality studies to investigate the association between levels of thyroid function parameters among individuals known for cumulative exposure to Pb.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-023-01113-8.

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^-ΔCt 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 (P = 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.

Reference values for Fatty Acids (FAs) are not well defined in the Indian population. Therefore, it is critical to establish FAs reference range for the healthy non-pregnant and pregnant Indian population. The present multi-centric, and cross-sectional study determines the 95% reference interval for FAs in an apparently pregnant Indian population and compare it to the healthy non-pregnant women. Physicians identified 164 reference individuals as healthy (56 non-pregnant and 108 pregnant) at various government and private hospitals of northern India. The 95th and 97.5th percentile reference limits were used to estimate the 95 percentile of the reference distribution. The reference ranges observed for Alpha-linolenic acid (0.29-0.42%; 0.36-0.58%), Docosahexaenoic-acid (3.38-4.23%; 3.8-4.55%), Eicosapentaenoic-acid (1.24-1.76%; 1.09-1.62%), Docosapentaenoic-acid-3 (0.61-0.69%; 0.65-0.76%), Linoleic-acid (18.44-20.75%; 19.51-21.88%), gamma-linolenic-acid (0.24-0.35%; 0.32-0.42%), Eicosatrienoic-acid (0.26-0.32%; 0.34-0.39%), Arachidonic-acid (9.29-11.02%; 10.02-11.56%), Docosatetraenoic-acid (0.62-0.89%; 0.79-1.09%), Docosapentaenoic-acid-6 (0.23-0.31%; 0.33-0.41%), Eicosatrienoic-acid (1.17-1.41%; 1.43-1.74%), Eicosenoic-acid (0.28-0.38%; 0.37-0.49%), Nervonic-acid (1.39-1.69%; 1.41-1.74%), Palmitoleic-acid (1.17-1.58%; 2-2.66%), Oleic-acid (19.8-22.26%; 19.68-22.94%), Myristic-acid (1.16-1.68%; 0.82-1.3%), Palmitic-acid (20.05-21.8%; 20.7-22.43%), Stearic-acid (11.34-12.56%; 10.29-11.02%), Arachidic-acid (0.17-0.2%; 0.18-0.23%), Lignoceric-acid (0.81-1.08%; 0.77-1.08%), trans-palmitoleic-acid (0.22-0.29%; 0.26-0.37%), trans-oleic-acid (0.55-0.72%; 0.68-0.84%), trans-linoleic-acid (0.38-0.54%; 0.42-0.59%) respectively for non-pregnant and pregnant women. Furthermore, total FAs were significantly (p ≤ 0:05) higher in women aged 31-45 years than in women aged 16-30 years. whereas, there was no significant change in total FAs profile based on omega-supplementation, diet category, preterm-birth history, and gestation period. Thus, the current study provides information about an individual who is deficient in FAs and the dose required to increase FA concentrations in the body.

Anti-mullerian hormone (AMH) has been proposed to add significance to diagnosis of PCOS in case of ambiguity. However, variable cutoffs of AHM among PCOS women have been reported. Using case-control design, this study investigated the diagnostic threshold of serum AMH levels among age matched 113 PCOS and 75 normo-ovulatory women and its correlation with clinical, hormonal and ultrasonographic parameters.PCOS was defined as per Rotterdam criteria 2003. Results depicted the mean serum AMH level to be significantly higher in PCOS group (7.84 ± 3.67vs. 3.23 ± 1.56 ng/mL) than controls. The AMH levels were positively(p = 0.001) associated with ovarian volume (r = 0.521) as well as number of ovarian follicles(r = 0.461). Further, serum AMH levels showed a positive correlation with luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (r = 0.206, p = 0.02), but no correlation significant with age, BMI,FG score and testosterone levels. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/ml with 86.7% sensitivity and 62.7% specificity. The mean level of AMH were highest among PCOS women with phenotype A (12.67 ± 3.46 ng/ml) with least among PCOS women displaying phenotype B(7.28 ± 1.60 ng/ml) where there is absence of PCOM. In conclusion, serum AMH levels are highly predictive of PCOM and high LH/FSH ratio among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01058-4.

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.

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors. The heterozygous state for Phe508del mutation in Exon 11 combination with Glu92Ala in Exon 4 resulted in epigenetic effect on atypical phenotype as PBS, a novel mutation identified in our case.

Myocardial infarction (MI) remains the most common cause of cardiac failure and continuous increasing rate of morbidity and mortality. We aimed to investigate the association of estrogen receptor-α (ESR1) gene polymorphism c454-397T>C with serum estradiol levels and dyslipidemia in 220 patients with MI in the age range of 35-70 years of both the genders. Genotyping study was performed through PCR-RFLP method using PvuII restriction enzyme. Serum estradiol level was estimated using the Access Sensitive Estradiol assay kit. Men patients had 43.2% increased risk for TC heterozygote in co-dominant (OR 10.66) and over-dominant models (OR 8.30), while women patients had 50% increased risk in co-dominant (OR 16.57) and over-dominant (OR 14.04) models. Variant C allele showed 25% increased risk of MI for in men (OR 2.24; CI 1.49-3.36; p = 0.0001), and 24% increased risk in women (OR 3.35; CI 1.95-5.76; p = 0.0001). Men patients had significantly increased serum estradiol levels compared to controls (25.28 ± 5.80 vs 17.04 ± 2.01; p < 0.0001). Significant difference was observed in estradiol levels between men and women patients (25.28 ± 5.80 vs 17.56 ± 3.32; p < 0.0001). Furthermore, significantly increased estradiol level was found in men patients compared to women for TT (25.46 ± 5.91 vs 16.71 ± 4.46; p < 0.0001), and TC genotypes (25.47 ± 5.91 vs 17.70 ± 2.86; p < 0.0001). Significantly increased HDL levels were observed in men patients with TC (43.10 ± 8.18 vs 38.91 ± 7.84; p < 0.01) and CC (47.16 ± 8.09 vs 38.91 ± 7.84; p < 0.001) genotypes compared to TT genotype. These findings suggest that TC heterozygote plays an important role as a genetic risk factor during MI pathogenesis in the South Indian population.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01104-1.