Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.

Association of serum C-reactive protein (CRP) and D-dimer concentration on the severity of COVID-19 cases with or without diabetes: a systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease (COVID-19) is a highly contagious disease that poses major public health risks. Fewer studies link high CRP and D-dimer levels to severe COVID-19 infection. Therefore, this study investigates the association of serum CRP and D-dimer concentration with COVID-19 severity in diabetic and non-diabetic patients. AREAS COVERED: Relevant published articles were identified using electronic search engines, such as Google Scholar, PubMed, Springer, Science Direct, and Researchgate. A total of 29 articles reporting on 15,282 patients (4,733 diabetes and 10,549 non-diabetes) were included in this systematic review and meta-analysis. RevMan V5.4, STATA V14 software, and SPSS V25 were used for the meta-analysis. Egger's regression and Begg-Mazumdar's test were used for assessing publication bias. The pooled result of all studies revealed that serum CRP (Standard mean difference (SMD) 0.41 mg/L; P < 0.0001; I2 93%) and D-dimer (SMD 0.32 mg/L; P < 0.0001; I2 83%) concentration was significantly higher in COVID-19 diabetic patients. The prevalence of COVID-19 infection was comparatively higher in male diabetic patients (OR 2.41; P < 0.00001; I2 88%). There was no publication bias. CRP and D-dimer rose with age in COVID-19 diabetic and non-diabetic patients. EXPERT OPINION: Overall, the serum CRP and D-dimer concentration in COVID-19 diabetic patients was significantly higher than non-diabetic patients indicating severe illness.

Obesity, a major risk factor for immunity and severe outcomes of COVID-19.

An influenza-like virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 disease and spread worldwide within a short time. COVID-19 has now become a significant concern for public health. Obesity is highly prevalent worldwide and is considered a risk factor for impairing the adaptive immune system. Although diabetes, hypertension, cardiovascular disease (CVD), and renal failure are considered the risk factors for COVID-19, obesity is not yet well-considered. The present study approaches establishing a systemic association between the prevalence of obesity and its impact on immunity concerning the severe outcomes of COVID-19 utilizing existing knowledge. Overall study outcomes documented the worldwide prevalence of obesity, its effects on immunity, and a possible underlying mechanism covering obesity-related risk pathways for the severe outcomes of COVID-19. Overall understanding from the present study is that being an immune system impairing factor, the role of obesity in the severe outcomes of COVID-19 is worthy.