Indian Journal of Clinical Biochemistry最新文献

Peru is one of the countries with the highest lead contamination in the world. Biological monitoring has limitations due to the shortage of laboratories with validated methodologies for the measurement of blood lead, and it is necessary to use alternative methods for its measurement in high-altitude cities. We aimed to compare the blood lead levels (BLL) measured by the LeadCare II (LC) method and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS). We measured the BLL of 108 children from the city of La Oroya. The mean and median BLL for GF-AAS were 10.77 ± 4.18 and 10.44 µg/dL, respectively; for the LC method, the mean was 11.71 ± 4.28 and the median was 11.60 µg/dL. We found a positive linear correlation (Rho = 0.923) between both methods. Notwithstanding, the Wilcoxon test suggests a significant difference between both methods (ρ = 0.000). In addition, the Bland-Altman analysis indicates that there is a positive bias (0.94) in the LC method, and this method tends to overestimate the BLL. Likewise, we performed a generalized linear model to evaluate the influence of age and hemoglobin on BLL. We found that age and hemoglobin had a significant influence on BLL measured by the LC method. Finally, we used two non-parametric linear regression methods (Deming and Passing-Bablok regression) to compare the LC method with the GF-AAS. We found that these methods differ by at least a constant amount, and there would be a proportional difference between both. Although in general there is a positive linear correlation, the results of both methods differ significantly. Therefore, its use in cities located at high altitudes (higher than 2440 m.a.s.l.) would not be recommended.

Neural tube defects (NTDs) are among the most prevalent and debilitating birth defects with their causes are still unknown, despite mounting evidence that genetic and/or environmental factors may play a role. We aimed to analyze two single nucleotide polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, serum folate and vitamin B12 status among a cohort of Egyptian children with NTDs and their mothers. A case-control study has been conducted on 50 Egyptian children with various types of NTDs and their mothers. They were comparable with 50 unrelated healthy, age and sex matched children and their mothers (50) selected as controls. Pediatric and neurosurgical assessments were performed to the included cases. Serum folate and vitamin B12 were measured using ELISA kits. MTHFR 677Cp<0.05 for all). Significantly higher frequencies of both heterozygous mutant (CT) and homozygous mutant (TT) genotypes, and mutant T allele of MTHFR 677Cp<0.05 for all), with lack of significant differences of this SNP between pediatric groups. Mutant homozygous (AA) genotype and mutant A allele of MTHFR 1298Ap<0.05 for both), with OR 6.081 and 7.071, [95%CI were 3.071-11.287 and 3.296-15.172, respectively]. Significantly frequent wild homozygous (CC) genotype and normal C allele of MTHFR 1298Ap<0.05 for both), with OR 0.231 and 0.754, [95%CI were 0.095-0.561and 0.432-1.317, respectively].Low serum folate and B12 are frequently common among children with NTDs and their mothers. MTHFR 677C

Abstract: The endoplasmic reticulum (ER) is the site for protein synthesis, its folding and secretion. An intricate set of signalling pathways, called UPR pathways, have been evolved by ER in mammalian cells, to allow the cell to respond the presence of misfolded proteins within the ER. Breaching of these signalling systems by disease oriented accumulation of unfolded proteins may develop cellular stress. The aim of this study is to explore whether COVID-19 infection is responsible for developing this kind of endoplasmic reticulum related stress (ER-stress). ER-stress was evaluated by checking the expression of ER-stress markers e.g. PERK (adapting) and TRAF2 (alarming). ER-stress was correlated to several blood parameters viz. IgG, pro- and anti-inflammatory cytokines, leukocytes, lymphocytes, RBC, haemoglobin and PaO₂/FiO₂ ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen) in COVID-19 affected subjects. COVID-19 infection was found to be a state of protein homeostasis (proteostasis) collapse. Changes in IgG levels showed very poor immune response by the infected subjects. At the initial phase of the disease, pro-inflammatory cytokine levels were high and anti-inflammatory cytokines levels were low; though they were partly compromised at later phase of the disease. Total leukocyte concentration increased over the period of time; while percentage of lymphocytes were dropped. No significant changes were observed in cases of RBC counts and haemoglobin (Hb) levels. Both RBC and Hb were maintained at their normal range. In mildly stressed group, PaO₂/FiO₂ ratio (oxygenation status) was in the higher side of normal range; whereas in other two groups the ratio was in respiratory distress syndrome mode. Virus could induce mild to severe ER-stress, which could be the cause of cellular death and systemic dysfunction introducing fatal consequences.

Graphical abstract: Schematic representation of SARS-CoV-2 infection and related consequences.

Buccal mucosa cancer has an aggressive nature as it rapidly grows and penetrates with high recurrence rate. Strikingly, carcinoma of buccal mucosa is the most common cancer of oral cavity in India. Recently, telomerase and telomere biology have been implicated in the pathogenesis and progression in various cancers via regulation of telomere maintenance by telomerase expression which is controlled by telomerase reverse transcriptase (TERT) promoter. Strikingly, h-TERT promoter mutations have been incriminated in regulation of telomerase gene expression. Here, we present a 35 years old male with intense coughing, short breathlessness and fever since 15 days, was admitted to the pulmonary unit. He was a chronic smoker and gutka user. The cytopathological analysis of gastric aspirate revealed buccal mucosa carcinoma of IV stage. We identified h-TERT promoter mutations in isolated genomic DNA from whole blood using DNA sequencer. Genetic analysis disclosed that h-TERT promoter region was highly mutated in this patient. Identified mutations include C.-248 del G, C.-272 del G, C.-279 del G, C.-331 del G, C.-349 del G, C.-351 del C, C.-360 G > A, C.-362 T > A, C.-371 del T and C.-372 del T. Further, all identified mutations were subjected to predict the pathologic functional consequences using bioinformatics tools viz TFsitescan and CiiiDER which showed either loss or gain of transcription factors binding sites in h-TERT promoter. This is a unique case in which total 9 mutations were observed in h-TERT promoter in a single case. In conclusion, all together these mutations in h-TERT promoter may alter the epigenetics and subsequently the tenacity of binding transcription factors which are of functional significance.

Growing number of research studies have shown that an anti-ageing gene Klotho (KL) is closely associated with Type 2 Diabetes Mellitus (T2DM). In this study, the association is genetically analyzed with single nucleotide polymorphism (SNP) of KL found in T2DM case of an Asian cohort. KL SNP information was obtained from a big database of the Korean Association Resource (KARE) from which 20 KL SNPs were available. Statistical analyses were conducted based on the 3 genetic models, such as additive, dominant, and recessive. Of the 20 KL SNPs, 12 SNPs were found to be significantly associated with T2DM in both of additive and dominant models. Odds ratios of the KL SNPs indicate increased susceptibility to T2DM in additive and dominant models. Significant association of KL with T2DM was further analyzed using imputed KL SNPs from HapMap reference data of the Eastern population. The statistically significant KL SNPs including the imputed SNPs distributed evenly over the KL gene area. The results in this study suggest klotho is a major player in the development of T2DM and the KL SNPs found in the case could be a risk marker of T2DM in the cohort.

Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets.

Despite being close to equator and receiving sufficient sun rays, evidences revealed that Indians have severe deficiency of vitamin D (vit D) ranging from 41 to 100% in different geographical locations. Therefore, in this study levels of 25(OH)D (physiologically measurable form) along with other bone metabolism associated biochemical markers were determined in serum sample of 300 apparently healthy study subjects (rural) from Doiwala block of Dehradun district in the state of Uttarakhand. Demographic data was also obtained based on a structured questionnaire to establish an association between 25(OH)D levels and various dietary and socio-cultural factors. Results demonstrated that of all study subjects, 197 (65%) had 25(OH)D levels below < 12 ng/mL (deficient) and 65 (21%) had 25(OH)D levels between 12 and 20 ng/mL (insufficient) with all other markers falling within respectively established reference ranges. Further, in univariate analysis, gender, occupation (indoor and outdoor), education were independently associated with vitamin D status. Additionally, parathyroid hormone associated significantly with gender and occupation, while calcium associated significantly with gender, occupation and education. Lastly, regression analysis revealed that gender and occupation independently associated with vitamin D status of subjects. In conclusion, apparently healthy subjects showed considerable vitamin D deficiency thereby generating an urgent need for formulating and implementing better government policies for enrichment of vitamin D levels among rural adults of Uttarakhand in future.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01048-6.

Human immunodeficiency virus (HIV) infection associated with weakened immune system due to decreased CD4 T cell count favors development of tuberculosis. Effector immune responses are also associated with micronutrient status due to their prominent role in maintaining immune functions. Micronutrient deficiencies are quite common among HIV patients that further result into compromised immunity thus making the conditions even more favorable for mycobacteria to establish disease. So, current study was designed to assess association of different micronutrients with development of TB in HIV patients. Micronutrient levels were measured in asymptomatic HIV patients who were monitored for the development of TB during follow up period (incident TB) within one month to one year and also in symptomatic microbiologically confirmed HIV-TB patients. Among various micronutrients assessed, levels of ferritin were found to be significantly increased (p < 0.05) with significant decreased zinc (p < 0.05) and selenium (p < 0.05) levels in incident TB group as well as in HIV-TB subjects compared to asymptomatic HIV patients who did not develop TB in the follow up period. Importantly, increased levels of ferritin and decreased levels of selenium were significantly associated with development of tuberculosis in HIV patients.

In 2019-2020, the novel "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)" had emerged as the biggest challenge for humanity, causing "coronavirus disease 19 (COVID-19)". Scientists around the world have been putting continuous efforts to unfold potential inhibitors of SARS-CoV-2. We have performed computational studies that help us to identify cyanobacterial photoprotective compounds as potential inhibitors against SARS-CoV-2 druggable target human angiotensin-converting enzyme (ACE2), which plays a vital role in the attachment and entry of the virus into the cell. Blocking the receptor-binding domain of ACE2 can prevent the access of the virus into the compartment. A molecular docking study was performed between photoprotective compounds mycosporine-like amino acids, scytonemins and ACE2 protein using AutoDock tools. Among sixteen molecularly docked metabolites, seven compounds were selected with binding energy < 6.8 kcal/mol. Afterwards, drug-likeness and toxicity of the top candidate were predicted using Swiss ADME and Pro Tox-II online servers. All top hits show desirable drug-likeness properties, but toxicity pattern analysis discloses the toxic effect of scytonemin and its derivatives, resulting in the elimination from the screening pipeline. Further molecular interaction study of the rest two ligands, mycosporine-glycine-valine and shinorine with ACE2 was performed using PyMol, Biovia Discovery studio and LigPlot+. Lastly biological activity of both the ligands was predicted by using the PASS online server. Combining the docking score and other studied properties, we believe that mycosporine-glycine-valine and shinorine have potential to be potent inhibitors of ACE2 and can be explored further to use against COVID-19.