Urine Zinc-alpha-2-glycoprotein as a potential biomarker for incipient diabetic nephropathy: A pilot study at a tertiary care hospital

Introduction: Urine albumin-creatinine ratio (UACR) continues to be used as ana indicator for detecting diabetic nephropathy (DN); however, damage starts much before that. Currently, no biomarkers are there to indicate incipient damage. As a result, researchers are looking for new biomarkers that could be used to detect DN threats sooner and perhaps hinder the development of end-stage renal disease. The present study intended to know if urine Zinc-alpha-2-glycoprotein (ZAG) levels correlate with glomerular filtration rate (GFR) in the study participants of type 2 diabetes mellitus (T2DM). Materials and Methods: The study included 68 participants with a known history of T2DM. Serum urea and creatinine levels, fasting plasma glucose, serum cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, glycated hemoglobin (HbA1c) and urine ZAG were estimated and UACR along with estimated GFR (eGFR) were calculated for all individuals. The characteristics of the study participants in the microalbuminuric and normoalbuminuric groups were compared. Results: The levels of urine ZAG in the microalbuminuric and normoalbuminuric groups were not observed to be substantially different. The relationship between urine ZAG and diabetes mellitus duration was found to be highly significant in normoalbuminuric patients. Urinary ZAG and correlation with categories of HbA1c % (good 9 poor) among normoalbuminuric individuals were not found to be significant. Conclusion: Despite previous research, we were unable to find a positive relationship between urinary ZAG concentrations and eGFR in this study. Prospective studies with greater sample sizes and follow-up are required to fully comprehend the possible use of ZAG as a biomarker in diabetic nephropathy

Natural products and potent analogs: Capacity to interrupt the Spike-human ACE2 complex, Protease, and RdRp targets of COVID-19 replication via molecular docking and MD Simulations

Looking at the severity of SARS-CoV-2 even after the approval of several vaccines like Covishield and Covaxin, there is a concern to find a fruitful remedy for treating infected people in the whole world to stop the spreading of this virus. In this piece of work, we systematically carried out the computational study of potent natural flavonoids Podocarflavone A and Rugosaflavonoid A and their analogs with many targets of COVID-19 such as main Protease (6LU7), S-protein and human ACE2 receptor Complex (6VW1), and RdRp (6M71), which are essential for the survival of nCov-19. MD simulations for 50ns were carried out in TIP3P to check their stability. Thermodynamic stability of the receptor-ligand complexes was evaluated with MMGBSA, and MMPBSA study. The Podocarflavone A and dihydrorugosaflavonoid analogs showed effective binding energy (DS -8.8 to -8.0 Kcal/mol) with S-protein and human ACE2 receptor Complex (6VW1), Protease (6LU7), and RdRp (6M71) of COVID-19. The comparative analysis with several standard antivirals such as remdesivir, oseltamivir, lopinavir, sofosbuvir, tenofovir, galidesivir, and favipiravir displayed that these natural analogs can be better antiviral for the COVID-19. This study demonstrated that halogenated Podocarflavone 2b (MMGBSA -40.93 Kcal/mol, MMPBSA -14.16 Kcal/mol) has comparable results with lopinavir (MMGBSA -43.15 Kcal/mol, MMPBSA -11.89 Kcal/mol). These compounds could be selected for wet-lab screening to develop as lead molecules in the initial infective stage with spike protein and replicative stage with RdRp of the n-Cov-19 virus

Age of Antibiotic Resistance in MDR/XDR Clinical Pathogen of <i>Pseudomonas aeruginosa</i>

Antibiotic resistance in Pseudomonas aeruginosa remains one of the most challenging phenomena of everyday medical science. The universal spread of high-risk clones of multidrug-resistant/extensively drug-resistant (MDR/XDR) clinical P. aeruginosa has become a public health threat. The P. aeruginosa bacteria exhibits remarkable genome plasticity that utilizes highly acquired and intrinsic resistance mechanisms to counter most antibiotic challenges. In addition, the adaptive antibiotic resistance of P. aeruginosa, including biofilm-mediated resistance and the formation of multidrug-tolerant persisted cells, are accountable for recalcitrance and relapse of infections. We highlighted the AMR mechanism considering the most common pathogen P. aeruginosa, its clinical impact, epidemiology, and save our souls (SOS)-mediated resistance. We further discussed the current therapeutic options against MDR/XDR P. aeruginosa infections, and described those treatment options in clinical practice. Finally, other therapeutic strategies, such as bacteriophage-based therapy and antimicrobial peptides, were described with clinical relevance

Genetic Variations in IL-1β, TNF-α, and TGF-β Associated with the Severity of Chronic Cervical Spondylitis in Patients

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1β (-511C/T), TNF-α (-308G/A), and TGF-β (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1β and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-β showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls