Indian Journal of Clinical Biochemistry最新文献

The new competency-based medical education undergraduate curriculum (CBMC) was launched for the 2019 admission batch of MBBS students. The programme is designed to create an "Indian Medical Graduate" (IMG) possessing the requisite knowledge, skills, attitudes, values and responsiveness, so that the graduate may function appropriately and effectively as a physician of first contact with the community while being globally relevant. Given that implementation of this curriculum is still in its infancy across the country, we stand to gain from a unified approach to its implementation. Phase I of the curriculum includes anatomy, physiology, and biochemistry along with professional and personal development modules. Biochemistry enjoys an enviable position in the medical curriculum as it explains the molecular basis of diseases. We present an appraisal of the curriculum in Biochemistry by reviewing the components against Harden's six themes which are considered when planning or developing a curriculum. Further, five core components of CBME are selected on the basis of three research papers to characterize underlying assumptions of CBME to suggest ways of logical implementation for achieving the competencies expected of the Indian Medical Graduate. The insight gained shall help students to be equipped with competencies which they shall be able to use in their day- to- day work, which shall ultimately help benefit patient care and the society at large.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01088-y.

Breast carcinoma is a heterogeneous disease that affects millions of women worldwide. Wilms' tumor 1 (WT1) is an oncogene that promotes proliferation, metastasis and reduces apoptosis. MicroRNAs (miR) are short noncoding RNAs with a major role in cancer metastasis. In present study, we investigated the association of serum level of WT1 with oxidative stress and expression of miR-361-5p in breast cancer. Serum samples of 45 patients and of 45 healthy women analyzed for protein level of WT1, malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant capacity (TAC). Serum and tissue expression of miR-361-5p in 45 tumor tissues and 45 paired non-tumor adjacent tissues and 45 serum samples of patients and healthy women analyzed by qRT-PCR. Protein levels of WT1 not significantly difference in serum of patients compared to healthy controls. Serum levels of MDA and TOS in patients were higher, but TAC level was lower than healthy controls (p < 0.001). There was a positive correlation between WT1 with MDA and TOS, and a negative correlation between WT1 with TAC in patients. miR-361-5p expression in tumor tissues and serum of patients was lower than non-tumor adjacent tissues and serum of healthy controls, respectively (p < 0.001). Moreover, there was a negative correlation between miR-361-5p and WT1 in patients. The positive correlation between WT1 with MDA and TOS and negative correlation between TAC and miR-361-5p suggests that this gene can play an important role in worse prognoses in breast cancer. Additionally, miR-361-5p may serve as an invasive biomarker for early detection of breast cancer.

Human oral squamous cell carcinoma is the sixth most frequent malignant cancer, with an unacceptably high death rate that affects people's health. Albeit, there are several clinical approaches for diagnosing and treating oral cancer they are still far from ideal. We previously synthesised and characterised the docetaxel nanoformulation (PLGA-Dtx) and discovered that docetaxel nanoencapsulation may suppress oral cancer cells. The goal of this study was to figure out the mechanism involved in the suppression of oral cancer cell proliferation. We discovered that PLGA-Dtx inhibited SCC-9 cell growth considerably as compared to free docetaxel (Dtx), and that the viability of SCC-9 cells treated with PLGA-Dtx was decreased dose-dependently. MTT assay showed that PLGA-Dtx selectively inhibited the growth of PBMCs from oral cancer patients while sparing PBMCs from normal healthy controls. Further, flow cytometry analysis showed that PLGA-Dtx induced apoptosis and necroptosis in SCC-9 cells. G2/M cell cycle arrest has been confirmed on exposure of PLGA-Dtx for 24 h in SCC-9 cells. Interestingly, western blot investigation found that PLGA-Dtx increased the amounts of necroptic proteins and apoptosis-related proteins more efficiently than Dtx. Furthermore, PLGA-Dtx was more effective in terms of ROS generation, and mitochondrial membrane potential depletion. Pretreatment with necroptosis inhibitor Nec-1 efficiently reversed the ROS production and further recover MMP caused by PLGA-Dtx. Overall, this study revealed a mechanistic model of therapeutic response for PLGA-Dtx in SCC-9 cells and proposed its potency by inducing cell death via activation of concurrent apoptosis and necroptosis in SCC-9 cells via TNF-α/RIP1/RIP3 and caspase-dependent pathway.

Cancer is the most common leading cause of mortality, making it a critical public health issue worldwide. Environmental and genetic abnormalities play a role in carcinogenesis, characterized by single nucleotide polymorphisms (SNPs) and abnormal gene expression. Also, non-coding RNA is a hot spot in cancer growth and metastasis. This study aimed to demonstrate the contribution of LncRNA H-19 rs2107425 to colorectal cancer (CRC) susceptibility and the correlation between miR-200a and LncRNA H-19 in patients with CRC. The current study was conducted on 100 participants, divided into 70 subjects with colorectal cancer and 30 age- and sex-matched healthy subjects. Patients with CRC experienced a significant elevation in WBC count, platelets, ALT, AST, and CEA. However, hemoglobin and albumin notably declined in patients with CRC compared with those in healthy controls. The expression of LncRNA H-19 and miR-200a increased in patients with CRC with a significant difference compared to healthy controls. Moreover, LncRNA H-19 and miR-200a expression significantly increased in stage III CRC compared to stage II CRC. As compared to carriers with the homozygous CC genotype, the frequency of rs2107425 CT and rs2107425 TT increased in patients with CRC. Our results indicate that the rs2107425 SNP of LncRNA H-19 may serve as a novel susceptibility marker for colorectal cancer. Moreover, miR-200a and LncRNA H-19 are prospective biomarkers of colorectal cancer.

Immune dysregulation is a key feature of the coronavirus disease-2019 (COVID-19). However, disparities in responses across ethnic groups are underappreciated. This study aimed to determine the relationship between chemokines and cytokines and the severity of COVID-19. Multiplex magnetic bead-based Luminex-100 was used to assess chemokine and cytokine levels in COVID-19 patients at admission (day-1) and after 4 days. The mean age of the patients recruited was 54.3 years, with 19 (63.3%) males. COVID-19 patients had significantly lower lymphocyte, monocyte, hemoglobin and eosinophil levels than controls (p < 0.05). COVID-19 patients showed significantly higher neutrophil levels than controls (p < 0.05). The baseline levels of IL-2, IL-6, IL-8, IL-10, and IFN-α/γ significantly increased in COVID-19 patients (p < 0.05). Chemokine levels (IP-10, MCP-1, MIG, and CCL-5) were significantly in COVID-19 patients. IL-8, IP-10, and MIG levels were significantly higher in the patients with severe COVID-19 (p < 0.05). Individuals with mild COVID-19 showed significantly higher levels of INF-α, IL-2, IL-6, and IL-8, whereas IL-10 levels were significantly lower (p < 0.05). TNF-levels decreased significantly in individuals with severe COVID-19, whereas IL-6, IL-8, and MIG levels increased (p < 0.05). After 4 days, INFα-, IL-2, IL-6, IL-8, IP-10, and MIG levels were significantly higher in patients with mild disease, whereas IL-6, MIG, and TNF-αlevels were significantly higher in patients with severe disease (p < 0.05). Thus, we conclude that COVID-19 is characterized by INF-α/γ, IL-6, IL-10, IP-10, MCP-1, MIG, and CCL5 dysregulation. IL-8, MIG, and IP-10 levels distinguish between moderate and severe COVID-19. Changes in INF-α, IL-2, IL-6, IL-8, IP-10, and MIG levels can be used to monitor disease progression.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01108-x.

SARS-CoV-2, an etiological agent of COVID-19, has been reported to inflict remarkably diverse manifestations in different subjects across the globe. Though patients with COVID-19 predominantly have fever, respiratory and constitutional symptoms, atypical presentations are becoming increasingly evident. COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation in moderate to severe symptomatic cases. In this case report, we are reporting thromboembolic complications of COVID-19 in a mild symptomatic subject incidentally diagnosed with mesenteric venous occlusion with no abdominal symptoms. Early recognition of the abdominal symptoms, diagnosis, initiation of anticoagulants, and timely surgical intervention may improvise the outcome in a patient with COVID-19 infection-induced mesenteric thrombosis. Superior mesenteric artery and venous thrombosis may lead to subsequent ischemia necessitating emergency laparotomy. Thus, the usage of low-dose anticoagulants in all the patients of COVID-19 irrespective of the categorization into mild, moderate, and severe COVID-19 disease should be considered.

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the β-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6-1258) as compared to MCOV-19 at 219.8 ng/ml (167.7-299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the mitogen-activated protein kinase (MAPK), plays a critical role in the severity of chronic inflammatory diseases such as diabetes mellitus (DM) and ARDS. The RAGE gene is most expressed in the alveolar epithelial cells (AECs) of the pulmonary system. Several clinical trials are now being conducted to determine the possible association between the levels of soluble isoforms of RAGE (sRAGE and esRAGE) and the severity of the disease in patients with ARDS and acute lung injury (ALI). In the current article, we reviewed the most recent studies on the RAGE/ligands axis and sRAGE/esRAGE levels in acute respiratory illness, with a focus on COVID-19-associated ARDS (CARDS) patients. According to the research conducted so far, sRAGE/esRAGE measurements in patients with CARDS can be used as a powerful chemical indicator among other biomarkers for assessment of early pulmonary involvement. Furthermore, inhibiting RAGE/MAPK and Angiotensin II receptor type 1 (ATR1) in CARDS patients can be a powerful strategy for diminishing cytokine storm and severe respiratory symptoms.

Reserpine, a bioactive compound isolated from the roots of Rauwolfia serpentine, is known to deplete dopamine, a neurotransmitter. The clinical application of reserpine has been associated to manage hypertension, insanity, insomnia and schizophrenia. However, the usage of reserpine as a drug is restricted because of its ability of inducing excess free radicals production and oxidative stress resulting into damage to liver and other organs. Here, we have explored the antioxidative potential of extract of garlic prepared using ethanol (EEG) against reserpine-induced hepatic damage in the albino Wister rats.The animals were divided into four different groups containing 6 animals in each: (1) control + placebo, (2) control + EEG, (3) reserpine and (4) reserpine with EEG. The reserpine treatment resulted into sharp increase in the level of MDA and significant reduction in the activitiesof key antioxidative enzymes (SOD, GST, and CAT) in the rat liver. It also caused sharp perturbations in the levels of certain hepatic transaminases (ALT, AST) and glycolytic LDH. The histopathological results revealed hepatic necrosis, which could have occurred due to reserpine induced lipid peroxidation as well as reduction in the levels of antioxidant species.The administration of EEG, however, significantly ameliorated reserpine induced hepatotoxicity. These results reflected the ameliorative property of EEG, which was probably mediated via its antioxidant function as it contains several bioactive molecules with free radical quenching potential.This study suggestedthe prospective application of EEG as a supplement to combat the side effects of reserpine.