Muhammad Ishtiaq Jan

Increased levels of oxalic acid are associated with an increased risk of kidney stone formation, which can lead to renal failure. In addition, its high concentration in the blood can lead to cardiovascular diseases. Therefore, it is vital to detect and quantify oxalic acid economically and rapidly. Copper oxide nanoparticles (CuONPs) are gaining importance as colorimetric nanosensors due to their intrinsic color change, cost-effectiveness, and easy synthesis. Paracetamol-mediated CuO NPs were synthesized through a new approach and characterized through various spectroscopic and morphological techniques. UV-visible spectroscopy confirmed the synthesis of CuO NPs through surface plasmon resonance at 225 nm. The peak at 850 cm⁻¹ corresponds to the stretching vibration of CuO NPs. The XRD and SEM characterization techniques confirmed the particle size of 27.51 nm with a spherical morphology. A machine learning-assisted strategy was developed with four prediction models: Random Forest, Linear Regression, XGBoost, and Decision Tree Regression. The intrinsic colorimetric features of CuO NPs were observed through the naked eye and quantified through spectroscopy with the addition of oxalate. The developed platform selectively detected oxalate levels in concentrations ranging from 1 to 120 µM, with a limit of detection (LOD) of 0.23 µM and a limit of quantification (LOQ) of 0.78 µM. The developed biosensor successfully quantified oxalate, crucial for diagnosing hyperoxaluria and preventing calcium oxalate stone formation in the kidneys. The machine learning complementary tools further bolster the accuracy of colorimetric concentration prediction.

Introduction: Atrial fibrillation (AFib) is a sustained form of cardiac arrythmia that occurs due to sympathetic overdrive, neurohumoral and electrophysiological changes. Sympatho-renal modulatory approach via miRNA-based therapeutics is likely to be an important treatment option for AFib. The study was aimed to unravel the common miRNAs as therapeutic targets involved in sympatho- renovascular axis to combat AFib. Methods: We employed the bioinformatics approach to discover differentially expressed genes (DEGs) from microarray gene expression datasets GSE41177 and GSE79768 of AFib patients. Concomitantly, genes associated with sympathetic cardio-renal axis, from Genetic Testing Registry (GTR) of National Center for Biotechnology Information (NCBI) were also analyzed. Overlapping miRNAs that target the maximum number of genes across all three pathological conditions perpetuating AFib were shortlisted. To confirm the reliability of the identified miRNAs, differential expression analysis was performed on miRNA expression profiles GSE190898, GSE68475, GSE70887 and GSE28954 derived from AFib patient samples. Results: ShinyGO analysis revealed enrichment in beta-adrenergic signaling, calcium signaling, as well as G protein-coupled receptor (GPCR) signaling involved in post synaptic membrane potential. The intersection of top 10 modules in miRNA-mRNA network revealed hub miRNAs having highest node degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC) scores. Differential expression analysis revealed hub miRNAs identified through integrated approach were found to be significantly dysregulated in AFib patients. Conclusion: This integrated approach identified 6 hub miRNAs, 4 reported (miR-101-3p, miR-23-3p, miR-27-3p, miR-25-3p) and 2 novel (miR-32-5p, miR-92-3p) miRNAs that might act as putative biomarkers for AFib.

The association of environmental and infectious health issues is increasing due to various hazardous metals, including cadmium, and microbial pathogens. Therefore, to cope with the concern of health problems, the fluorescence carbon dots (CDs) were developed and characterized using the green carbon source of Momordica charantia L. through hydrothermal approaches. The developed CDs were investigated for sensing cadmium (II) (Cd ²⁺ ) in real water samples and antibacterial activities against Escherichia coli , Pseudomonas aeruginosa , Streptococcus mutans , and Klebsiella pneumonia using the well diffusion method. The results demonstrated that the average size of the developed CDs was 21.4 nm. The fluorescence intensity of CDs was successfully quenched through the CDs/Cd ²⁺ complex via the inner filter effect. The developed fluorescence probe has wide linearity for detecting Cd ²⁺ in the concentration range of 0.1–30 µg/mL with a detection limit of 30 ng/mL. The synthesized CDs only inhibited the growth of E. coli with maximum concentrations of 500 µg/mL, with zones of inhibition of 28 ± 0.12 mm. The fabricated fluorescent sensor provides a simple, rapid, economical, eco‐friendly, and sensitive platform for detecting Cd ²⁺ in the environmental field and for the treatment of bacterial infections caused by E. coli .

Zinc oxide nanoparticles (ZnO NPs) are becoming an innovative agent in biological and environmental applications due to its unique characteristics, biocompatibility, low cost and toxicity. In this study, the composite ZnO NPs using Rhododendron arboreum (R. arboreum) stem bark were synthesized and characterized for UV–visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The biomedical assessment of the synthesized nanoparticles showed zones of inhibition of 23 ± 0.09, 18 ± 0.1 and 16 ± 0.05 mm, against the Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains, respectively. Likewise, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against K. pneumoniae, S. aureus, and E. coli were found to be 34 ± 0.21 and 72.71 ± 0.47, 47 ± 0.11 and 94.86 ± 0.84 and 94 ± 0.18 and 185.43 ± 0.16 µg/mL, respectively. The biosynthesized ZnO NPs resulted in significant eradication of the outer and inner membranes of the tested bacterial cells. In addition, the environmental application of the synthesized ZnO NPs also showed time-dependent photocatalytic degradation activity and revealed 65% methyl orange dye degradation with an irradiation period of 6 h. The findings of this study suggest the suitability of the novel R. arboreum stem bark-based ZnO NPs as an effective ameliorant against bactericidal activities and photocatalytic potential for the removal of potentially toxic substances from water.

SARS-CoV-2 infection affects and modulates serum as well as hematological parameters. However, whether it modifies these parameters in the existing disease conditions, which help in the erection of specific treatments for the disease, is under investigation. Here, we aimed to determine whether serum and hematological parameters alteration in various diseases, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD) and myocardial infarction (MI) conditions correlate and signal SARS-CoV-2 infection, which could be used as a rapid diagnosis tool for SARS-CoV-2 infection in disease conditions. To assess the projected goals, we collected blood samples of 1,113 male and female patients with solo and multiple disease conditions of DM/HTN/IHD/MI with severe COVID-19, followed by biochemical analysis, including COVID-19 virus detection by RT-qPCR. Furthermore, blood was collected from age-matched disease and healthy individuals 502 and 660 and considered as negative control. In our results, we examined higher levels of serum parameters, including D-dimer, ferritin, hs-CRP, and LDH, as well as hematological parameters, including TLC in sole and multiple diseases (DM/HTN/IHD/MI) conditions compared to the control subjects. Besides, the hematological parameters, including Hb, RBC, and platelet levels, decreased in the patients. In addition, we found declined levels of leukocyte count (%), lymphocyte (%), monocyte (%), and eosinophil (%), and elevated level of neutrophil levels (%) in all the disease patients infected with SARS-CoV-2. Besides, NLR and NMR ratios were also statistically significantly (p < 0.05) high in the patients with solo and multiple disease conditions of DM/HTN/IHD/MI infected with the SARS-CoV-2 virus. In conclusion, rapid alteration of sera and hematological parameters are associated with SARS-CoV-2 infections, which could help signal COVID-19 in respective disease patients. Moreover, our results may help to improve the clinical management for the rapid diagnosis of COVID-19 concurrent with respective diseases.

Zinc nanoparticles (ZnNPs) open new opportunities for biomedical applications as a strategy against microbes and dye removal in an efficient way. The composite ZnNPs using Rhododendron arboreum (R. arboreum) stem bark were synthesized and characterized for UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized nanoparticles showed zones of inhibition of 23±0.09, 18±0.1 and 16±0.05 mm, against the Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against K. pneumoniae, S. aureus, and E. coli were found to be 34±0.21 and 72.71±0.47, 47±0.11 and 94.86±0.84 and 94±0.18 and 185.43±0.16 µg/mL, respectively. The biosynthesized ZnNPs resulted in significant eradication of the outer and inner membranes of the bacterial cells. Likewise, the synthesized ZnNPs showed time-dependent photocatalytic degradation activity and revealed 65% methyl orange dye degradation with an irradiation period of 6 hours. The findings of this study suggest the suitability of the novel R. arboreum stem bark-based ZnNPs as an effective ameliorant against bactericidal activities and photocatalysts for the removal of hazardous water contaminants.

Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood. The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments. HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dl), triglycerides (45.45 ± 0.39 mg/dl), LDL-c (66.12 ± 0.10 mg/dl), VLDL-c (19.34 ± 0.16 mg/dl), and a decrease in HDL-c (10.34 ± 0.18 mg/dl). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dl), triglycerides (32.33 ± 0.16 mg/dl), LDL-c (50.34 ± 0.15 mg/dl) and VLDL-c (13.15 ± 0.45 mg/dl) respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dl). 15-oxo ursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol). It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats which might lead to new medication with significant hypolipidemic potential.

It is important to develop new antibacterial drugs since the emergence of bacterial resistance to available antibiotics. Metal nanoparticles have the potential to combat antibiotic resistance and are effective antibacterial agents. Here, we demonstrate the biogenic production of zinc nanoparticles using Rhododendron arboreum stem bark. The biosynthesized ZnNPs were characterized through different analytical techniques such as UV-vis, FTIR, EDX, SEM, and XRD. Clinical isolates such as E. coli, S. aureus, and K. pneumonia were used to check the antibacterial efficacy of the biosynthesized zinc nanoparticles. The MIC and MBC values against K. pneumonia, S. aureu, and E. coli were found to be 34±0.21 and 11.71±0.47, 47±0.11 and 23.86±0.84 and 94±0.18 and 40.43±0.16 µg/mL, respectively. It dramatically decreased the integrity of the cell membrane and markedly increased the permeability of both inner and outer membranes. The green synthesized ZnNPs have good catalytic activity. It degraded 65% of methyl orange dye within 6h when the mixture was kept in direct sunlight, thus demonstrating good photodegradation potential and can be employed as a good photocatalyst. According to these results, biosynthesized zinc nanoparticles could be a potential therapy option for controlling bacterial pathogenesis and an effective photocatalyst for the elimination of hazardous water contaminants.

Bacterial resistance to antibiotics and host defense systems is primarily due to bacterial biofilm formation in antibiotic therapy. In the present study, two complexes, bis (biphenyl acetate) bipyridine Cu (II) (1) and bis (biphenyl acetate) bipyridine Zn (II) (2), were tested for their ability to prevent biofilm formation. The minimum inhibitory concentration and minimum bactericidal concentration of complexes 1 and 2 were 46.87 ± 1.822 and 93.75 ± 1.345 and 47.87 ± 1.345 and 94.85 ± 1.466 μg/mL, respectively. The significant activity of both complexes was attributed to the damage caused at the membrane level and was confirmed using an imaging technique. The biofilm inhibitory potential levels of complexes 1 and 2 were 95% and 71%, respectively, while the biofilm eradication potential levels were 95% and 35%, respectively, for both complexes. Both the complexes showed good interactions with the E. coli DNA. Thus, complexes 1 and 2 are good antibiofilm agents that exert their bactericidal actions possibly by disrupting the bacterial membrane and interacting with the bacterial DNA, which can act as a powerful agent to restrain the development of bacterial biofilm on therapeutic implants.

The aim of the current study was to evaluate therapeutic potentials of Hydroxyquinoline Sulfanilamide (HSM) for Alzheimer’s disease in a mice model of Streptozotocin (STZ)-induced diabetes. The antioxidant analysis of mice brain homogenates was carried out by catalase (CAT) assay, reduced glutathione (GSH) assay, and lipid peroxidation (LPO) assay. Biochemical analysis of blood plasma was conducted by peroxidase (POD) assay and superoxide dismutase (SOD) assay. The expression of mice brain proteins was evaluated using Western Blotting analysis. The administration of HSM increased the activity of antioxidant enzymes including CAT, SOD, GSH, and POD and lowered LPO actions. These findings indicate that STZ may lead to diabetes in mice, followed by hypercholesterolemia, expressed as triglycerides in mice blood. However, HSM significantly decreased STZ-induced hyperglycemia and hypercholesterolemia in adult albino mice. The data confirmed that HSM lowered STZ-induced oxidative stress, inhibited phosphorylated JNK, NF-kB, and upregulated Nrf-2 to improve and restore the synapse and memory defects in adult albino mice. Conclusively, the current findings suggested that HSM is a safe, novel, and potential drug candidate against metabolic dysfunction and induced cognitive impairment.