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Indian Journal Of Clinical Biochemistry[JOURNAL]

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Diagnostic Utility of Serum Ferritin in Identifying Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD): A Cross-Sectional Study Using National Health and Nutrition Examination Survey (NHANES-2017-2020) Data.

Ramasamy J

Indian J Clin Biochem · 2025 Jan · PMID 39835224 · Full text

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease worldwide. There are conflicting reports on the association of serum ferritin levels and its utility in discrimina... UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease worldwide. There are conflicting reports on the association of serum ferritin levels and its utility in discriminating various stages of liver fibrosis in patients with NAFLD. This study is done to address the conflicts by analysing the National Health and Nutritional Examination Survey 2017-2020 (NHANES 2017-2020) data. The survey data was screened, and the eligible participants (n = 5901) were categorized based on the controlled attenuation parameter (CAP) obtained from Vibration Controlled and Transient Elastography (VCTE) scan into 2 groups, NAFLD (CAP ≥ 274 dB/m, n = 2528) and non-NAFLD (CAP < 274 dB/m, n = 3373). The NAFLD group had a significantly higher proportion of obese, diabetic, and metabolic syndrome participants. Serum ferritin levels were significantly higher in the NAFLD group, and the levels showed an upward trend from simple steatosis to significant fibrosis. Multivariate regression analysis showed that ferritin has a significant positive association with the median liver stiffness parameter (LSM), which is the index of liver fibrosis. Receiver operator characteristic curve (ROC) analysis showed that serum ferritin levels are a poor predictor of fibrosis (LSM > 8 kPA) in those with NAFLD (AUC = 0.59, Sensitivity = 53.5%, Specificity = 60.3%). To conclude, serum ferritin levels were positively associated and it trended upward as the disease progressed from simple steatosis to fibrosis in NAFLD. However, its diagnostic utility in discriminating liver fibrosis in patients with NAFLD is limited. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01159-8.

Redefining the Reference Interval and Cut-Off Values of the Hematological and Biochemical Parameters and Deriving a Sensitive Predictive Marker for Crisis Events in Sickle Cell Disease.

Patel S, Chandrakar D, Wasnik PN … +4 more , Mohapatra E, Nanda R, Shah S, Gupta A

Indian J Clin Biochem · 2025 Jan · PMID 39835223 · Full text

UNLABELLED: The heterogeneity in clinical presentations in sickle cell disease (SCD) alters between crisis and steady state phases. Considering the pathophysiology, it is crucial to establish a disease-specific reference... UNLABELLED: The heterogeneity in clinical presentations in sickle cell disease (SCD) alters between crisis and steady state phases. Considering the pathophysiology, it is crucial to establish a disease-specific reference interval for hematological and biochemical parameters and identify the sensitive predictive markers for crisis. The case-control study included fifty-four healthy control, forty SCD cases in crisis state, and forty-six steady state cases. Blood samples were evaluated for complete blood count (CBC) and biochemical parameters. Red cell indices were calculated. 2.5th and 97.5th percentile values were delineated in the steady state cases as new reference interval. The new cut-off values were evaluated for sensitivity and specificity. The steady state cases reported a significant decrease in urea, sodium, Hb, Hct, and RBC count compared to the control group, whereas potassium, and red cell indices were higher. Compared to the steady state, the crisis state depicted a significant increase in urea, liver enzymes, leucocytes, inflammatory indices, and all red cell indices, whereas sodium, albumin, iron, Hb, Hct, and LMR were decreased. The revised 95 percentile ranges were sodium-132.35-143.65 mmol/L, potassium-3.75-6.09 mmol/L, albumin-2.9-5.0 g/dL, Hb-7.51-12.17 g/dL, RBC count-2.2-5.49 × 10/µL, and Hct-22.54-36.1%. Red cell indices like Ricerca, Green and King, and Huber-Heklotz could be good screening tools for crisis events with more than 70% sensitivity. Thus, the laboratory must derive a new reference interval and cut-off values at the steady state in the SCD population it is catering samples rather than comparing it with normal healthy individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01158-9.

Study of Glabranin as an Inhibitor Against Prostate Cancer: Molecular Docking, Molecular Dynamics Simulation, MM-PBSA Calculation and QSAR Prediction.

Browne RB, Goswami N, Borah P … +1 more , Roy JD

Indian J Clin Biochem · 2024 Jul · PMID 39641116 · Full text

UNLABELLED: Prostate cancer is the World's second most frequent malignancy, with the fifth-highest male mortality rate. In advanced prostate cancer patients, point mutations such as T877A and W741L are prevalent, imparti... UNLABELLED: Prostate cancer is the World's second most frequent malignancy, with the fifth-highest male mortality rate. In advanced prostate cancer patients, point mutations such as T877A and W741L are prevalent, imparting treatment resistance and hence promoting cancer development. The emergence of drug resistance in prostate cancer necessitates the development of suitable ligands to allow for stronger interactions with the receptors, which can inhibit cancer progression. The present study focuses on flavonoids produced by plants, which may act as inhibitors of point mutations like T877A and W741L in prostate cancer. This research was conducted using an in-silico method where the compound Glabranin and its derivatives were virtually screened to identify potential drugs for combating such point mutations. Thirty-five Molecular Dockings were performed to find the ligand-receptor complexes with the lowest binding energy. Moreover, employing a variety of tools, ligands were evaluated for drug-likeness and toxicity, indicating a promising drug candidate. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, eight structures were subjected to a 100 ns Molecular Dynamics simulation. A QSAR analysis was also performed based on the simulation findings. In this study, it was revealed that GlaMod2 phytocompound was effective against T877A and W741L mutations in prostate cancer. It was observed that the phytocompound was stable and had potential properties for the development of a novel drug to combat prostate cancer and drug resistance This phytocompound may therefore be effective in the development of prostate cancer inhibitors for patients with mutant androgen receptors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01134-3.

Sweet Bell Pepper: A Focus on Its Nutritional Qualities and Illness-Alleviated Properties.

Younes AH, Mustafa YF

Indian J Clin Biochem · 2024 Oct · PMID 39346723 · Full text

Sweet bell pepper (SBP, L.) can be employed as a spice in many dishes and may also be eaten as a delicious fruit. These two nutritional attributes are owing to the strong, deep taste of many SBP phytochemicals. This fru... Sweet bell pepper (SBP, L.) can be employed as a spice in many dishes and may also be eaten as a delicious fruit. These two nutritional attributes are owing to the strong, deep taste of many SBP phytochemicals. This fruit has many additional beneficial properties because it contains high concentrations of minerals and vitamins that distinguish it from other kinds of fruits. Almost every part of the SBP is thought to be an excellent source of bioactive substances that are health supporters, such as flavonoids, polyphenols, and various aromatic substances. The ability of SBP-phytochemicals to work as antioxidants, reducing the harmful effects of oxidative stress and consequently preventing many chronic illnesses, is one of their main biomedical characteristics. These phytochemicals have good antibacterial properties, mostly against gram-positive pathogenic microbes, in addition to their anti-carcinogenic and cardio-preventive effects. So, this review aims to highlight the nutritional qualities of SBP-derived phytochemicals and their illness-alleviated characteristics. Antioxidant, anti-inflammatory, antitumor, antidiabetic, and analgesic properties are some of the ones discussed.

Anti-tumor Effects of Polyphenols via Targeting Cancer Driving Signaling Pathways: A Review.

Moar K, Yadav S, Pant A … +2 more , Deepika, Maurya PK

Indian J Clin Biochem · 2024 Oct · PMID 39346722 · Full text

The use of drugs in chemotherapy poses numerous side effects. Hence the use of natural substances that can help in the prevention and cure of the disease is a dire necessity. Cancer is a deadly illness and combination of... The use of drugs in chemotherapy poses numerous side effects. Hence the use of natural substances that can help in the prevention and cure of the disease is a dire necessity. Cancer is a deadly illness and combination of diseases, the menace of which is rising with every passing year. The research community and scientists from all over the world are working towards finding a cure of the disease. The use of polyphenols which are naturally derived from plants have a great potential to be used as anti-cancer drugs and also the use of fruits and vegetables which are rich in these polyphenols can also help in the prevention of diseases. The study aims to compile the available literature and research studies on the anti-cancer effects of polyphenols and the signaling pathways that are affected by them. To review the anti-cancer effects of polyphenols, Google Scholar, PubMed and ScienceDirect were used to study the literature available. The article that have been used for literature review were filtered using keywords including cancer, polyphenols and signaling pathways. Majorly articles from the last 10 years have been considered for the review but relevant articles from earlier than 10 years have also been considered. Almost 400 articles were studied for the review and 200 articles have been cited. The current review shows the potential of polyphenols as anti-cancer compounds and how the consumption of a diet rich in polyphenols can help in the prevention of cancer. Because of their capacity to affect a variety of oncogenic and oncosuppressive signaling pathways, phytochemicals derived from plants have been effectively introduced as an alternative anticarcinogenic medicines.

Assessing Performance of Martins's and Sampson's Formulae for Calculation of LDL-C in Indian Population: A Single Center Retrospective Study.

Sankanagoudar S, Tomo S, Syiemlieh A … +3 more , Sharma PP, Banerjee M, Sharma P

Indian J Clin Biochem · 2024 Oct · PMID 39346721 · Full text

Various formulae had been derived to calculate the LDL-C from other lipid profile parameters to supplant the need for direct estimation. Martin's, Sampson's, and Cordova's formulae are recently derived formulae for calcu... Various formulae had been derived to calculate the LDL-C from other lipid profile parameters to supplant the need for direct estimation. Martin's, Sampson's, and Cordova's formulae are recently derived formulae for calculating LDL-C. However, no study has been undertaken till now to verify the newer formulae viz. Martins's and Sampson's in Indian population. The retrospective cross-sectional study was carried out after obtaining approval from the Institutional Ethics Committee on human subject research. The lipid profile data were collected for a period of 17 months from January 2020 to May 2021. The formulae proposed by Friedewald, Cordova, Anandaraja, Martin, and Sampson were used to assess calculated LDL-C. Intraclass correlations were performed to assess the effectiveness of each formula when compared with direct estimation. In our study, we observed that LDL-C calculated using Martin was observed to be closer to that of direct estimation. The bias observed was lowest for Martin's formulae, followed by Sampson's. Intraclass correlation analysis for absolute agreement demonstrated Cordova, Martin, and Sampson to have an average ICC > 0.9, with Martin, and Sampson having a value < 0.05. Martin fared superior to other formulae in intraclass correlation in patients with LDL > 70. In patients with TG below 200 mg/dL, Martin, and Sampson had a significant correlation with comparable average ICC. However, in patients with TG > 300 mg/dL, Cordova appears to fare better than all other formulae. Our study demonstrated a distinctly superior performance of Martin's formula over Friedewald's formula in the Indian patient population.

Phytochemical Screening, HPTLC Fingerprinting and Evaluation of In Vitro Cytotoxic Activity of Stem Bark Extracts of O (L.) Vent. Against Human Cervical Cancer Cells.

Gam S, Kumar S, Kushari S … +4 more , Dutta RS, Sarma H, Paul A, Zaman MK

Indian J Clin Biochem · 2024 Oct · PMID 39346720 · Full text

a well-known traditional medicinal plant which is used to alleviate various kinds of diseases in Asia. The study aimed to identify bioactive compounds present in stem bark using HPTLC technique. Further, the cytotoxic e... a well-known traditional medicinal plant which is used to alleviate various kinds of diseases in Asia. The study aimed to identify bioactive compounds present in stem bark using HPTLC technique. Further, the cytotoxic effects of the plant extracts were determined against HeLa (human cervical carcinoma) cell lines. The results of the study have shown the presence of the phytoconstituents such as flavonoids, phenols, tannins and steroids. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay showed that the ethanol, methanol and water extracts of exhibited cytotoxic effect in HeLa cell lines with IC values of 119, 89.43 and 114.1 µg/mL, respectively against standard doxorubicin with IC value 3.895 µg/mL. The current study suggests that the methanol extract of may offer chemopreventive properties. However, additional research is required to isolate and characterize the specific chemical entities present in . These studies will aid in identifying a potential lead compound that holds promise as a natural anticancer agent.

Double Trouble: Unravelling the Health Hazards of Microplastics and Heavy Metals.

Mitra P, Gupta S, Sharma P

Indian J Clin Biochem · 2024 Oct · PMID 39346719 · Full text

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Biochemical and Pharmacological Assessments of Tramadol Abuse on Human Male Fertility: Relation to Seminal Plasma 8-Hydroxyguanosine and Zinc.

Hassan MH, Saadeldin AA, Alsagheer G … +2 more , Desoky T, Hasan AS

Indian J Clin Biochem · 2024 Oct · PMID 39346718 · Full text

UNLABELLED: Tramadol is a pain killing drug highly used worldwide. There is a knowledge gap for fertility consequences of analgesic addiction in men. In this observational study, we investigated the hazards of tramadol a... UNLABELLED: Tramadol is a pain killing drug highly used worldwide. There is a knowledge gap for fertility consequences of analgesic addiction in men. In this observational study, we investigated the hazards of tramadol abuse on human male reproductive function. A total of 30 tramadol addicts and 30 healthy controls have participated in the study. History and clinical examination of the included subjects were performed. Biochemical and molecular assays were measured in all participants include serum reproductive hormones (calculated free testosterone, FSH, LH, prolactin and estradiol) using ELISA techniques, semen analysis, seminal plasma zinc and selenium assays using colorimetric kits, seminal plasma tramadol concentrations using Gas Chromatography-Mass Spectrometry (GC-MS), and seminal plasma 8-hydroxyguanosine (8-OHG) using high performance liquid chromatography were measured. Tramadol abuse significantly decreased semen parameters quality. Additionally, tramadol abuse significantly decreased testosterone ( = 0.001) and increased prolactin serum levels ( = 0.000). Tramadol abusers showed significantly higher levels of 8-OHG ( < 0.0001) with significantly lower levels of zinc and selenium in their seminal plasma compared with the controls ( < 0.0001, and 0.0002 respectively). Also, tramadol addicts displayed positive correlations between seminal plasma levels of 8-OHG (r = 0.905,  = 0.00) and sperm abnormal forms (r = 0.610,  = 0.000) with seminal plasma tramadol levels. Seminal plasma levels of zinc (r = - 0.815,  = 0.00), sperm motility (r = - 0.484,  = 0.007), and vitality (r = - 0.430,  = 0.018) were negatively correlated with seminal plasma levels of tramadol. Our data suggest that tramadol abuse may impair male fertility by increasing oxidative damage of sperms and reducing testosterone and the antioxidants trace elements in testicular tissues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01141-4.

Effect of Unmetabolized Folic Acid on Immunoinflammatory Markers in Sickle Cell Disease Patients Taking Folic Acid Supplementation.

Chandrakar D, Patel S, Wasnik PN … +4 more , Mohapatra E, Nanda R, Shah S, Gupta DL

Indian J Clin Biochem · 2024 Oct · PMID 39346717 · Full text

Folic acid (FA) supplementation in sickle cell disease (SCD) patients lead to accumulation of unmetabolized folic acid (UMFA) which might influence the level of cytokines and NK cell activity and thus trigger the crisis... Folic acid (FA) supplementation in sickle cell disease (SCD) patients lead to accumulation of unmetabolized folic acid (UMFA) which might influence the level of cytokines and NK cell activity and thus trigger the crisis event. The aim of the study was to investigate the effect of UMFA levels on immuno-inflammatory markers in SCD patients taking FA supplementation. The cross-sectional study was conducted on 60 HbSS confirmed SCD cases with 22 crisis and 38 cases at steady state of 15-40 years age group. Serum FA, 5-Methyl Tetrahydrofolate (5-MTHF), Dihydrofolate reductase, Interleukin-6 (IL-6), Highly sensitive C-Reactive Protein (HsCRP), and natural killer (NK) cell activity were estimated. More than 50% of the study population depicted presence of UMFA. The median UMFA level was significantly elevated in crisis group (131.8 ng/mL) as compared to the steady state group (36.31 ng/mL) ( = 0.041). The median value of HsCRP was significantly higher in the crisis group (18.41 mg/L) than the steady state group (2.04 mg/L) ( = 0.003). Similarly, IL-6 was higher in crisis group (13.29 pg/mL) than steady state group (5 pg/mL) ( = 0.060). The median NK cell activity was 39.28 nmol/L in crisis group and 35.31 nmol/L in steady state groups ( = 0.889). In bivariate correlation analysis, UMFA showed a significant negative correlation with NK cell activity (r = - 0.638;  =  < 0.001) and a positive correlation with IL-6 (r = 0.571;  = 0.001) and HsCRP (r = 0.237;  = 0.200). Accumulation of UMFA affect NK cell activity, thus influence the vulnerability for crisis state. Therefore, dosage modification for FA supplementation in SCD patients is suggested.

Correlation of Diabetes Related Factors with Vitamin D and Immunological Parameters in T2DM Kashmiri Population.

Tarfeen N, Ul Nisa K, Masoodi SR … +3 more , Bhat H, Wani S, Ganai BA

Indian J Clin Biochem · 2024 Oct · PMID 39346716 · Full text

In this study, the role of inflammatory biomarkers and vitamin D in Type 2 diabetes mellitus (T2DM) and their correlation with diabetes related factors (HbA1c, FPG, and insulin) was analysed. In this study, Kashmiri pati... In this study, the role of inflammatory biomarkers and vitamin D in Type 2 diabetes mellitus (T2DM) and their correlation with diabetes related factors (HbA1c, FPG, and insulin) was analysed. In this study, Kashmiri patients with T2DM and healthy individuals were considered as cases (n = 100) and controls (n = 100) respectively. Blood samples from both groups were collected, inflammatory biomarkers (TNF-α, CRP), as well as serum vitamin D levels, were estimated by ELISA. From our results it was revealed that patients with T2DM had significantly lower serum vitamin D levels than control groups (<0.05). Pro-inflammatory cytokine levels, including TNF-α and CRP, were seen to be elevated reaching a level of statistical significance (<0.05). On correlating the HbA1c, FPG and insulin with TNF-α, CRP and vitamin D, significant positive correlation (<0.05) was found between TNF-α and CRP with HbA1c and FPG in patients, non-significant positive correlation (>0.05) was observed between insulin with TNF-α, and vitamin D and weak negative correlation with CRP in case study group. On correlating the impact of vitamin D on HbA1c and FPG levels, non-significant weak negative correlation was observed in patient group than controls, indicating that patients with lower vitamin D levels have higher HbA1c, showing that lower vitamin D have some role in etiology of T2DM.

Assessment of Diagnostic Accuracy and Clinical Utility of DNA Methylation (5-mC) in Detecting Severity of Occupational Lead Exposure.

Kalahasthi R, Adepu VK, Nagaraju R

Indian J Clin Biochem · 2024 Oct · PMID 39346715 · Full text

This study investigated the diagnostic accuracy (DA) and clinical utility (CU) of DNA methylation (5 methylcytosine) in occupational Pb-exposure from Pb based industry. Blood Lead levels (BLLs) were measured using the IC... This study investigated the diagnostic accuracy (DA) and clinical utility (CU) of DNA methylation (5 methylcytosine) in occupational Pb-exposure from Pb based industry. Blood Lead levels (BLLs) were measured using the ICP-OES method. The total DNA methylation (5-mC) was quantified using ELISA method. Based on their BLLs, the Pb-exposed workers were categorised into three groups: low (< 10 µg/dL), moderate (10-30 µg/dL), and high exposure (> 30 µg/dL). DNA methylation (5-mC) was significantly lower in moderate and high Pb-exposure groups when compared to the low Pb-exposure group. Workers exposed to high levels of Pb-exposure, the DA variables of 5-mC showed that the sensitivity was 74.7% [95% CI 65.4-84.0], specificity was 69.6% [95% CI 50.8-88.4], positive predictive value (PPV) was 89.9% [95% CI 82.7-97.0], Postive likelihood ratio (LR+) was 2.454 [95% CI 1.3-4.6], and diagnostic odds ratio (DOR) is 6.3 [95% CI 6.5-7.7]. In moderate Pb-exposure, the DA variables of 5-mC revealed that the sensitivity is 64.9% [95% CI 55.2-74.5], the specificity is 69.6% [95% CI 50.8-88.4], the PPV is 89.7% [95% CI 82.5-97.0], the LR+ is 2.132 [95% CI 1.13-4.03], and the DOR is 4.2 [95% CI 3.6-5.7]. The high Pb-exposure group had higher DA metrics when compared to moderate Pb exposure. The clinical utility (CU+) of 5-mC was found to have good utility of 0.671 [95% CI 0.566-0.776] in the high Pb exposure group and fair utility of 0.582 [95% CI 0.470-0.694] in moderate Pb exposure group. In conclusion, DNA methylation (5mC) could be used as a predictive biomarker for high Pb-exposure.

Role of the AMP-Activated Protein Kinase in the Pathogenesis of Polycystic Ovary Syndrome.

Jalil AT, Zair MA, Hanthal ZR … +4 more , Naser SJ, Aslandook T, Abosaooda M, Fadhil A

Indian J Clin Biochem · 2024 Oct · PMID 39346714 · Full text

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by elevated androgen levels, menstrual irregularities, and polycystic morphology of the ovaries. Affecting 6-10% of women in childbearing age, PCOS is... Polycystic ovary syndrome (PCOS) is a complex disorder characterized by elevated androgen levels, menstrual irregularities, and polycystic morphology of the ovaries. Affecting 6-10% of women in childbearing age, PCOS is a leading cause of infertility worldwide. In recent years, there has been a growing acknowledgment of the involvement of adenosine monophosphate-activated protein kinase (AMPK) in the development of polycystic ovary syndrome (PCOS). The expression of AMPK is diminished in polycystic ovaries, and when AMPK is silenced in human granulosa cells, there is a rise in the expression of steroidogenic enzymes, resulting in increased production of estradiol and progesterone. Additionally, in mouse models, the inhibiting AMPK intensifies the polycystic appearance of ovaries and impairs the process of ovulation. Moreover, it has been shown that AMPK activators like metformin and resveratrol ameliorate PCOS associated signs and symptoms in experimental and clinical studies. These findings, collectively, indicate the key role of AMPK in the pathogenesis of PCOS. Understanding the role of AMPK in PCOS will offer rewarding information on details of PCOS pathogenesis and will provide novel more specific therapeutic approaches. The present review summarizes the latest findings regarding the role of AMPK in PCOS obtained in experimental and clinical studies.

Identification of Novel Biomarkers Using Serum and Urinary Proteomics for Early Detection of Hypoxic Ischemic Encephalopathy.

Gurtoo S, Kotimoole CN, Sahana KS … +1 more , Arun AB

Indian J Clin Biochem · 2024 Oct · PMID 39346713 · Full text

UNLABELLED: Hypoxic-ischemic encephalopathy (HIE) is a severe birth complication affecting neonates. Around 40-60% of affected neonates die by two years of age or have severe disabilities and neurodevelopmental delays. T... UNLABELLED: Hypoxic-ischemic encephalopathy (HIE) is a severe birth complication affecting neonates. Around 40-60% of affected neonates die by two years of age or have severe disabilities and neurodevelopmental delays. The early assessments of brain injury using traditional clinical and biochemical indicators do not always align with its severity and recovery. This delays identifying neonates who may benefit from adjuvant therapeutic strategies and monitoring therapy response. Our aim was to identify specific proteins using proteomic approach to predict the severity of neonatal asphyxia so that its outcome can also be prevented. To achieve this goal a case-control study was conducted on 38 neonates, and serum and urine samples were collected within 24 h of life. Clinical findings, biochemical parameters, and outcomes of the neonates were recorded. A tandem mass spectrometry-based quantitative proteomics approach was used to identify proteins in the serum and urine of HIE neonates. Bioinformatics analyses were performed to assess the potential features and competence of the identified differentially expressed proteins. This resulted in identification of 51 differentially expressed proteins which were found common to both serum and urine proteomic data. Some of the promising biomarkers found were APOD, ORM1, SOD1, and FABP1. These proteins were associated with the pathways like Amyloid fiber formation, diseases of programmed cell death, detoxification of reactive oxygen species, and neurodegenerative diseases. This study will pave the way for identifying the biomarkers (proteins) that can screen neonates for brain injury and monitor the disease progression, which may reduce mortality and neurodevelopmental impairment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01143-2.

Effects of Dietary Zinc Deficiency and Supplementation on Prepubertal Rat Testes: Sulfhydryl and Antioxidant Status.

Kumari D, Nair N, Bedwal RS

Indian J Clin Biochem · 2024 Oct · PMID 39346712 · Full text

The study was designed to investigate the effects of dietary zinc deficiency and supplementation on antioxidant system viz. superoxide-dismutase, glutathione reductase, glutathione peroxidase, glutathione- S-transferase,... The study was designed to investigate the effects of dietary zinc deficiency and supplementation on antioxidant system viz. superoxide-dismutase, glutathione reductase, glutathione peroxidase, glutathione- S-transferase, catalase and sulfhydryls levels (GSH, TSH, NPSH and PBSH) in testes of Wistar rats. Pre-pubertal rats were divided into two groups with 6 sub-groups each viz. zinc control (ZC), pair fed (PF), zinc deficient (ZD), zinc control supplementation (ZCS), pair-fed supplementation (PFS) and zinc deficient supplementation (ZDS). Experiments were set for 2- and 4-weeks followed by 4 weeks of zinc supplementation. The zinc deficient group animals exhibited significant decrease in gonado-somatic index (2- and 4- weeks), sulfhydryls levels, GSH, GPx, GR (2 and 4-weeks) and GST concentration (2-weeks). However, after zinc supplementation significant improvement in gonadosomatic index, SH, GSH, antioxidant enzyme levels (GR, GPx, and GST) in deficient groups has been observed. Zinc deficiency during pre-pubertal period affected growth and caused dysregulation of the glutathione antioxidant system. The significant alterations in the levels of antioxidant enzymes and non-enzymatic antioxidant system (GSH and SH) in zinc deficient groups could be due to alleviated generation of free radicals, causative factor for increased oxidative stress which may lead to infertility as oxidative stress is a common pathology seen during infertility. Altered antioxidant system and sulfhydryls levels in testes due to dietary zinc deficiency reflect the significance of optimum zinc for maintaining homeostatic balance in gonadal physiology. Supplementing zinc for 4 weeks could reduce the redox imbalance which may help in alleviating oxidative stress induced alterations in testes.

Circulating miRNA-373 and Vascular Endothelial Growth Factor as Potential Biomarkers for Early Detection of Breast Cancer.

Raheem AR, Abdul-Rasheed OF, Khattab OS … +3 more , Alsammarraie AZ, Al-Aubaidy H, Abid HA

Indian J Clin Biochem · 2024 Oct · PMID 39346711 · Full text

UNLABELLED: Breast cancer is the leading cause of cancer-related mortality among women worldwide. MicroRNAs (miRNAs), short non-coding RNAs, have been implicated in cancer-related processes such as tumor development, met... UNLABELLED: Breast cancer is the leading cause of cancer-related mortality among women worldwide. MicroRNAs (miRNAs), short non-coding RNAs, have been implicated in cancer-related processes such as tumor development, metastasis, angiogenesis, and drug resistance. Circulating miRNA-373 demonstrates higher relative exosomal serum levels in breast cancer patients compared to healthy women, making it a potential non-invasive biomarker. Separately, vascular endothelial growth factor (VEGF) is crucial for angiogenesis, and is elevated in breast cancer. In this case-control study, we aimed to investigate the diagnostic accuracy of miRNA-373 and VEGF as biomarkers for early-stage breast cancer detection. Serum samples were collected from 120 participants, comprising 30 breast cancer patients, 30 benign breast tumor patients, and 60 healthy controls, over the period of April 2022 to January 2023. MiRNA-373 expression was analyzed by reverse transcription-quantitative PCR with GAPDH normalisation, while VEGF levels in serum samples were measured by ELISA. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of both biomarkers. MiRNA-373 expression (∆Ct) differed significantly between the three groups (breast cancer: - 12.20 ± 1.11; benign tumors: - 12.79 ± 1.09; controls: - 13.64 ± 0.93). ROC analysis revealed moderate discriminative power for miRNA-373 (specificity = 76.7%; sensitivity = 70.0%; AUC = 0.839) and excellent discriminative power for VEGF (specificity = 85.0%; sensitivity = 90.0%; AUC = 0.944) in distinguishing early-stage breast cancer patients from healthy controls. In summary, this study demonstrates the promising potential of miRNA-373 as an early diagnostic biomarker for breast cancer detection, requiring further validation in larger cohorts. Our findings also reinforce the diagnostic value of circulating VEGF levels for breast cancer screening. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-023-01174-9.

TRAIL C1595T Variant Critically Alters the Level of sTRAIL in Terms of Histopathological Parameters in Colorectal Cancer.

Horozoglu C, Yildiz A, Sonmez D … +4 more , Demirkol S, Yildiz Y, Arikan S, Yaylim I

Indian J Clin Biochem · 2024 Oct · PMID 39346710 · Full text

TRAIL, a member of the TNF family, is expressed in tumor and tumor surrounding tissue in many solid organ cancers. While the induction of tumor-specific apoptosis in correlation with cytokine stimulation may cause anti-t... TRAIL, a member of the TNF family, is expressed in tumor and tumor surrounding tissue in many solid organ cancers. While the induction of tumor-specific apoptosis in correlation with cytokine stimulation may cause anti-tumoral effects, the pro-tumorigenic effects of its expression by tumor surrounding tissue members have been reported in the literature. In our study, it was aimed to evaluate the effect of the gene variant of TRAIL on soluble levels in patients with colorectal cancer (CRC) on the molecular pathological axis. TRAIL C1595 gene variant PCR-RFLP and sTRAIL levels were determined by ELISA in age and sex adjusted CRC and control groups. It was determined that CT carriage was high in patients without perineural invasion and sTRAIL levels were approximately 2.72 times lower than CC in patients with CT in this group ( < 0.05). Similarly, sTRAIL level was found to be high in patients with CC genotype in CRC without lymph node metastas. It was determined that CT carriage was high in patients without perineural invasion and sTRAIL levels were approximately 2.49 times lower than CC in patients with CT in this group.is ( < 0.05). We think that TRAIL C1595T in CRC can change sTRAIL levels in the clinicopathological axis in advanced stages such as metastasis and invasion, but both are not independent risk factors.

Exploring Micronutrient Dynamics in COVID-19 Severity and Mortality: Unraveling the Roles of Vitamin D, Calcium, Phosphorus, Magnesium and ALP.

Kumar PK, Japa P, Tomo S … +12 more , Sankanagoudar S, Purohit P, Charan J, Purohit A, Nag VL, Bhatia PK, Singh K, Dutt N, Garg MK, Misra S, Sharma P, Yadav D

Indian J Clin Biochem · 2024 Oct · PMID 39346709 · Full text

UNLABELLED: The COVID-19 pandemic has underscored the critical importance of understanding the intricate relationship between micronutrient levels and disease outcomes. This study explores the impact of Vitamin D, calciu... UNLABELLED: The COVID-19 pandemic has underscored the critical importance of understanding the intricate relationship between micronutrient levels and disease outcomes. This study explores the impact of Vitamin D, calcium, phosphorus, magnesium, and alkaline phosphatase (ALP) on COVID-19 severity and mortality. The study involves 200 participants (100 COVID-19 patients, 100 controls), we meticulously analyzed micronutrient dynamics. Calcium, phosphorus, magnesium and ALP was measured spectrophotometrically. Vitamin D was measured using Chemiluminescent method. The study reveals that diminished levels of calcium, phosphorus, magnesium, and with elevated ALP, are significantly associated with COVID-19 cases. Whereas the Vitamin D levels in severe group was increased when compared to mild cases but decreased than control group. Disease severity correlated with declining calcium (r = - 0.35,  < 0.01), phosphorus (r = - 0.26,  < 0.05), and magnesium (r = - 0.21,  < 0.05), and increased ALP (r = 0.42,  < 0.001). Post-discharge, calcium ( < 0.05) and phosphorus ( < 0.01) showed positive trends, while ALP ( < 0.001) decreased. Notably, calcium (OR = 0.63,  < 0.05) and ALP (OR = 1.87,  < 0.001) emerged as significant predictors of disease severity. The findings not only illuminate potential therapeutic avenues but also emphasize the need to optimize nutrient levels, including magnesium, for COVID-19 prevention and management. Given the complexities of these relationships, further rigorous exploration, including well-designed trials and understanding underlying mechanisms, is imperative to unravel the dynamics of these nutrient interactions in the context of COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-024-01225-9.

Optimization of Automated Dimethylmethylene Blue Assay for Quantification of Pediatric Urine Samples.

Indika NR, Peiris H, Deutz NEP … +1 more , Perera R

Indian J Clin Biochem · 2024 Oct · PMID 39346708 · Full text

The metachromatic dye dimethylmethylene blue is used to quantify total glycosaminoglycans in urine. Understanding the interaction of dimethylmethylene blue with glycosaminoglycans is pertinent to optimize the assay proce... The metachromatic dye dimethylmethylene blue is used to quantify total glycosaminoglycans in urine. Understanding the interaction of dimethylmethylene blue with glycosaminoglycans is pertinent to optimize the assay procedure depending on the type of sample and interpret the findings meaningfully. The present spectrophotometric study determined the optimum sample-to-dye ratio, primary wavelength for measuring absorbance, after studying the interaction of two different chondroitin sulfate species (unfractionated chondroitin sulfate from bovine trachea vs. chondroitin sulfate oligosaccharide with degree of polymerization of 12, from shark cartilage) with dimethylmethylene blue. Respective dye-glycosaminoglycan complexes of the two chondroitin sulfate species showed significantly different absorbance maxima, while that of the chondroitin sulfate oligosaccharide was closer to absorbance maxima of urine glycosaminoglycans. The chondroitin sulfate oligosaccharide showed relatively less stable absorbance readings at higher concentrations in the reaction volume. Furthermore, the chondroitin sulfate reference materials exhibited differences in the linearity of standard curves and hence parallelism. Based on the findings, the method was semiautomated on Beckman Coulter D✕C 700 biochemistry analyzer using the chondroitin sulfate oligosaccharide as the standard. The urine glycosaminoglycan concentration obtained was slightly lower but reasonably close to that obtained through the External Quality Assurance (EQA) scheme administrated by ERNDIM (European Research Network, Inherited Disorders of Metabolism). The findings of the present study can be used to guide the dimethylmethylene blue assay optimization, redevelopment efforts, and harmonization across laboratories. The chondroitin sulfate oligosaccharide is better than the unfractionated chondroitin sulfate from bovine trachea due to its absorbance maxima closer to urine glycosaminoglycans. On the other hand, unfractionated chondroitin sulfate exhibit poor parallelism leading to falsely lower urine glycosaminoglycan levels.

Are Altered Expression of Vascular Endothelial Growth Factor and Placental Growth Factor Associated with Placental Angiogenesis in Recurrent Pregnancy Loss?

Sultana S, Renjini Devi MR, Rathod MK … +2 more , Reddy PP, Ananthapur V

Indian J Clin Biochem · 2024 Jul · PMID 39005877 · Full text

Angiogenesis is one of the most important steps during pregnancy for placental and fetal development. Based on the hypothesis that vascular insufficiency and altered angiogenesis may lead to early pregnancy loss, the pre... Angiogenesis is one of the most important steps during pregnancy for placental and fetal development. Based on the hypothesis that vascular insufficiency and altered angiogenesis may lead to early pregnancy loss, the present study was aimed to understand the role of Vascular endothelial growth factor (VEGFA) and Placental growth factor (PLGF) gene expression in placental angiogenesis in the pathogenesis of Recurrent pregnancy loss (RPL). Gene expression analysis of VEGFA and PLGF was carried out in the placental tissue collected from 30 women with recurrent pregnancy loss and compared with the placenta obtained from 16 women with medically terminated pregnancy. The mRNA expression of both VEGFA and PLGF genes were significantly downregulated in the placenta of recurrent pregnancy loss in comparison to the placenta of medically terminated pregnancies. In conclusion the results of the present study suggest that altered expression of VEGFA and PLGF genes in placenta disturb the angiogenesis and contribute to the pathogenesis of recurrent pregnancy loss.
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