Identification of Genetic Variants in Exon 4 of TP53 in Lung Carcinoma and in Silico Prediction of Their Significance.

Lung cancer is a severe and the leading cause of cancer related deaths in men and women all over the world. Tumor suppressor protein (TP53) encoded by the TP53 gene which plays a pivotal role in various cellular tumor suppression processes viz cell cycle arrest and apoptosis. Henceforth, the present study was aimed to TP53 exon4 variants from lung carcinoma. Histopathologic and clinically proven 20 patients of lung cancer were enrolled in this study the average age of patients was 45 ± 8 years which categorized as early onset of lung cancer. Genomic DNA was isolated from the blood specimen of patients. Extracted DNA was subjected to PCR amplification for exon 4 of TP53 using appropriate primers and subsequently amplified products were applied to nucleotide alterations via using the DNA sanger sequencing. The genetic analysis documented five variants in exon4 of TP53 which include viz. 4 substitutions [c.215 > C at codon 72, C. 358-359AA > GG at codon 120] were highly prevalent, occurring in 63% and 25% frequency in patients. Other two variants viz. C. 358 A > C at codon 120, C. 365T > G at codon 122 were present at frequency of 15% whilst one deletion variant [152 del C] was found with 5% frequency. Furthermore, alterations on codon 72, 120,122 and 51 were characterized as possibly damaging by Poly Phen-2 and decreased stability using stability bioinformatic tool. Taken together all these findings infer that TP53 gene involved in modulation and susceptibility to lung cancer.

Direct Relationship Between Uric Acid and C-Reactive Protein and Its Implication in the Chronic Kidney Disease.

Chronic Kidney disease (CKD) is a serious life threatening disease associated with morbidity and mortality in India. Hypothetical relationship between serum uric acid and C-Reactive protein (CRP) levels has been demonstrated in the pathophysiology of CKD. Fifty chronic kidney disease patients before dialysis and fifty controls were executed for measurement of serum uric acid and C-Reactive protein as well as other biochemical parameters analysis. Serum C-Reactive protein was measured by quantitative turbidimetric immunoassay. In this study, serum uric acid, creatinine, urea and C-Reactive protein levels were significant raised in CKD group to that of controls. Notably serum C-Reactive protein levels were significantly higher in the CKD patients associated with non-diabetic factors in comparison to diabetic associated CKD patients. A receiver operating characteristic curve (ROC) exhibited a strong association between uric acid and C-Reactive protein levels. A strong direct relationship between serum uric acid and C-Reactive protein in CKD patients are plausibly culprits in the progression of diseases.

An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy.

Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Recent studies have revealed that SARS-CoV-2 infection is associated with the generation of thrombosis and coagulopathy. Fundamentally, it has been believed that a diverse array of signalling pathways might be responsible for the activation of coagulation cascade during SARS-CoV-2 infection. Henceforth, a detailed understanding of these probable underlying molecular mechanistic pathways causing thrombosis in Covid-19 disease deserves an urgent exploration. Therefore, in this review, the hypothetical crosstalk between distinct signalling pathways including apoptosis, inflammation, hypoxia and angiogenesis attributable for the commencement of thrombotic events during SARS-CoV-2 infection has been addressed which might further unravel promising therapeutic targets in Covid-19 disease.

Ayurvedic lipid based rasayans - A perspective on the preparation and pharmacological significance of lipids on the bioavailability of phytoconstituents.

For thousands of years, lipid based Ayurvedic formulations have been made in India, and the craft has survived down the millennia up to the present time. Some of these deliciously potent phytonutrient preparations are very popular and have sustained the test of time pertaining to their efficacy. Recent researches on the role of phytonutrients in promoting cardio-pulmonary, brain and immune health substantially buttress the philosophy underlying the use of lipids in preparing these emulsions, since a large number of these bioactives are lipophilic. Being lipoidic, they are absorbed through the lacteals in the small intestine, and are then transported through the thoracic duct directly to the heart, bypassing the liver. The formulations utilizing ghee (clarified butter) or sesame oil as the carrier lipid, either while frying the myrobalams or as Anupana (adjuvant), have special significance in modulating bodily immunity, since the immune system is housed in lymphatics which are lipid rich. Amla and lipid based Ayurvedic rasayans (rejuvenating formulations) are a popular and highly palatable group of phytonutraceutical preparations. This group of polyherbal adaptogenic formulations is classified separately from other formulations in Ayurvedic therapeutics. Several of these health-promoting rasayans are suitable to be consumed by all age-groups in the recommended season and dose. Current research on endothelial and immune cell receptor mediated uptake of lipoidic molecules, together with the knowledge of lipid absorption pathways, lends credence to the usefulness of rasayans in targeting the cardio-pulmonary and immune systems. An attempt has been made in this paper to elucidate the mechanisms underpinning the complex interplay between lipid delivered hydrophobic phyto-molecules, systemic lymphatics and the Immune system.

Gut Microbiota and Alzheimer's Disease: Experimental Evidence and Clinical Reality.

Alzheimer's disease (AD) is characterized by progressive death of neuronal cells in the regions of the brain concerned with memory and cognition, and is the major cause of dementia in the elderly population. Various molecular mechanisms, metabolic risk factors and environmental triggers contributing to the genesis and progression of AD are under intense investigations. The present review has dealt with the impact of a highly discussed topic of gut microbiota affecting the neurodegeneration in the AD brain. A detailed description of the composition of gut bacterial flora and its interaction with the host has been presented, followed by an analysis of key concepts of bidirectional communication between gut microbiota and the brain. The substantial experimental evidence of gut microbiota affecting the neurodegenerative process in experimental AD models has been described next in this review, and finally, the limitations of such experimental studies vis-avis the actual disease and the paucity of clinical data on this topic have also been mentioned.

Analysis of performance of clinical biochemistry laboratory using Sigma metrics and Quality Goal Index.

BACKGROUND: Unreliable and ingenuine results issued by clinical laboratories have serious consequences for the patients. Sigma metrics is a standardized tool for Quality assessment for test performance in a laboratory. OBJECTIVE: To evaluate the performance of routine biochemistry laboratory at MMIMSR, Mullana in terms of Sigma metrics and Quality Goal Index. MATERIAL AND METHODS: This cross sectional study evaluated performance of 14 routine chemistry parameters using retrospective Internal Quality Control data of two levels on Siemens Dimension Rxl from Feb to Jul 2019 for CV% and EQAS reports from CMC, Vellore for Bias%. Sigma metrics was calculated using total allowable error targets as per CLIA and Biological Variability database guidelines. RESULTS: For level-2 IQC; TG, Chol, ALP showed excellent performance with σ â€‹> â€‹6 while σ â€‹< â€‹3 was observed for AST, Total Protein, Glucose, BUN and ALT using CLIA guidelines while in IQC Level-3 poor performers were only BUN and ALT with Ca, TG and Chol showing σ â€‹> â€‹6. Further by using Biological Variability data guidelines; 10 parameters of IQC Level-2 and 5 of IQC level-3 were poor performers with σ â€‹< â€‹3. CONCLUSION: Sigma metrics is an excellent tool for performance analysis of tests performed in a clinical laboratory. Lack of precision in terms of CV% was seen for majority of the poor performers. Total allowable error targets using Biological Variability data revealed σ â€‹< â€‹3 for 10 parameters while using CLIA guidelines σ â€‹< â€‹3 was seen for only 5 parameters of IQC level-2.

Alpha-Synuclein as a Biomarker of Parkinson's Disease: Good, but Not Good Enough.

Parkinson's disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

COVID-19 in India: Are Biological and Environmental Factors Helping to Stem the Incidence and Severity?

The ongoing Corona virus (COVID-19) pandemic has witnessed global political responses of unimaginable proportions. Many nations have implemented lockdowns that involve mandating citizens not to leave their residences for non-essential work. The Indian government has taken appropriate and commendable steps to curtail the community spread of COVID-19. While this may be extremely beneficial, this perspective discusses the other reasons why COVID-19 may have a lesser impact on India. We analyze the current pattern of SARS-CoV-2 transmission, testing, and mortality in India with an emphasis on the importance of mortality as a marker of the clinical relevance of COVID-19 disease. We also analyze the environmental and biological factors which may lessen the impact of COVID-19 in India. The importance of cross-immunity, innate immune responses, ACE polymorphism, and viral genetic mutations are discussed.

Effect of BMI and urinary pH on urolithiasis and its composition.

Urolithiasis is a common urological disease predominantly affecting males. The lifetime risk of urolithiasis varies from 1% to 5% in Asia, 5% to 9% in Europe, 10% to 15% in the USA and 20% to 25% in the middle-east; lowest prevalence is reported from Greenland and Japan. Such differences have been explained on the basis of race, diet and climate factors. Furthermore, changing socio-economic conditions have generated changes in the prevalence, incidence and distribution for age, sex and type of lithiasis in terms of both the site and the chemical as well as the physical composition of the calculi. The aim of our study was to determine the association between body mass index (BMI) and urine pH in patients with urolithiasis and the influence of body size, as reflected by the BMI, on the composition. The study was conducted in the Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research, on urolithiatic patients. The data included patient's age, sex, BMI, urine pH, serum calcium, serum uric acid, serum creatinine and stone composition. Data from 100 patients, 70 men (70%) and 30 women (30%), were analyzed, with 28 patients having normal weight, 38 patients being overweight and 34 patients being obese. The mean age of the patients was 36.58 ± 9.91 years in group I, 40.47 ± 14.48 years in group II and 37.85 ± 12.46 years in group III (P > 0.05). The stone composition was calcium oxalate (CaOx) in 66 patients, calcium phosphate (CaP) in 60 patients, uric acid (UA) in 38 patients, combined calcium oxalate and calcium phosphate in 28 patients and three stones in 10 patients. The urinary pH levels (mean ± SD) were 7.78 ± 1.49 in group I, 7.15 ± 1.11 in group II and 6.29 ± 1.14 in group III patients (P = 0.0001). Urine pH showed a stepwise decrease with increasing BMI (inverse correlation). Urine pH is inversely related to BMI among patients with urolithiasis, as is the occurrence of urate, calcium oxalate and calcium phosphate stones. Similarly, the serum creatinine increased as the BMI and number of stones increased among the study population.

To establish the reference range of glycated hemoglobin.

Background: Diabetes mellitus (DM) has emerged as a major healthcare problem in India. There were an estimated 40 million persons with DM in India in 2007 and this number is predicted to rise to almost 70 million by 2025. It is estimated that every fifth person with diabetes will be an Indian. The objective of the present investigation was to establish the reference range for glycated hemoglobin (HbA1C) in healthy non-diabetic subjects in our hospital laboratory and compare it with the values reported by standard laboratories. Methods: The study was conducted in the Department of Biochemistry, MMIMSR, Mullana (Ambala, Haryana). Total number of subjects was 50 (25 males, 25 females), aged 30 to 70 years. 2 ml of blood was collected from antecubital vein under aseptic conditions from each subject and put in EDTA vials. Hemolysed blood was estimated by semiautoanalyzer for HbA1C. Results: In females, the levels were 6.50 ± 0.74 % while in males the levels were 6.27 ± 0.94 %. The overall range in females was 4.8 - 7.56 % while in males it was 4.2 to 7.56 %. The values were comparable (p>0.05) with those reported by standard laboratories, e.g. Dr. Lal PathLabs (<6%), Charak diagnostic (4.5-6.3%) and Mayo Clinic (6.5-7%). Conclusion: Our laboratory levels of HbA1C are comparable with the reference range of different laboratories and hence suitable to be used as cut-offs while interpreting the results of patients with DM.