Cobalt oxide modified sulfur and phosphorus Co-doped g-C3N4 for screening of urinary human albumin.

The fabrication of a heteroatom-doped nanocomposite based on cobalt oxide modified sulfur, phosphorus co-doped carbon nitride (Co3O4/SP-CN) with increased active sites is reported. The synthesized nanocomposite offers surprisingly high electrocatalytic oxidation efficacy toward human albumin (HA) despite its agglomeration. This improved efficacy of Co3O4/SP-CN nanocomposite could be attributed to its increased adsorption sites and surface defects, fast charge transportation capability, and conductivity. Additionally, morphological and compositional analysis of the fabricated Co3O4/SP-CN material has been performed  through scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photon spectroscopy (XPS), and Raman spectroscopy. The fabricated electrode shows remarkable amperometric response against the HA with a limit of detection of 8.39 nM and linear range of 20-4000 nM at applied potential of 0.25 V versus Ag/AgCl in 0.1 M PBS (pH 8.2). The designed Co3O4/SP-CN electrode has been successfully applied to monitor HA in  urine samples of diabetic patient with recovery percentage from 94.1 and 92.1% and with relative standard deviation (RSD) values of 5.8 and 7.8%. According to the best of our knowledge, this is the first report to use a Co3O4/SP-CN-based graphitic pencil (GP) electrode for monitoring of HA for early diagnosis of diabetic nephropathy.

Co-Doped CeO2/Activated C Nanocomposite Functionalized with Ionic Liquid for Colorimetric Biosensing of H2O2 via Peroxidase Mimicking.

Hydrogen peroxide acts as a byproduct of oxidative metabolism, and oxidative stress caused by its excess amount, causes different types of cancer. Thus, fast and cost-friendly analytical methods need to be developed for H2O2. Ionic liquid (IL)-coated cobalt (Co)-doped cerium oxide (CeO2)/activated carbon (C) nanocomposite has been used to assess the peroxidase-like activity for the colorimetric detection of H2O2. Both activated C and IL have a synergistic effect on the electrical conductivity of the nanocomposites to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The Co-doped CeO2/activated C nanocomposite has been synthesized by the co-precipitation method and characterized by UV-Vis spectrophotometry, FTIR, SEM, EDX, Raman spectroscopy, and XRD. The prepared nanocomposite was functionalized with IL to avoid agglomeration. H2O2 concentration, incubation time, pH, TMB concentration, and quantity of the capped nanocomposite were tuned. The proposed sensing probe gave a limit of detection of 1.3 × 10-8 M, a limit of quantification of 1.4 × 10-8 M, and an R2 of 0.999. The sensor gave a colorimetric response within 2 min at pH 6 at room temperature. The co-existing species did not show any interference during the sensing probe. The proposed sensor showed high sensitivity and selectivity and was used to detect H2O2 in cancer patients' urine samples.

Supramolecular solvent-based liquid phase extraction of antimony prior to spectrophotometric quantification.

Antimony (Sb) is highly hazardous to human health even in minute concentration. Therefore, its accurate and precise determination in the real environmental samples is of immense importance. In this work for the first time, UV-Vis spectrophotometric method was developed for the quantification of Sb(III) from water samples using supramolecular solvent (undecanol-tetrahydrofuran)-based extraction. The maximum absorption wavelength for antomony-diathizone complex was found to be 590 nm having molar absorptivity of 3.1 × 104 L.mol.cm-1. Factors affecting extraction efficiency like solution sample volume, amount of chelating agent, pH, matrix effect, and type and volume of supramolecular solvent were determined and optimized. Analytical parameters like limit of detection (0.19 µg L-1), limit of quantification (0.62 µg L-1), pre-concentration factor (15), enhancement factor (15), and relative standard deviation for 8 successive analysis (0.8%) were calculated under optimized experimental conditions. The method was applied to real water samples like tap water of laboratory, waste water from Kohat hospitals, and dam water (Tanda dam Kohat) with quantitative addition recovery (94-100%).

Non-enzymatic electrochemical dopamine sensing probe based on hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure.

A non-enzymatic dopamine electrochemical sensing probe was developed. A hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure was prepared by a facile hydrothermal approach. The combination of Zn, which has an abundance of electrons, and Co3O4 exhibited a synergistically electron-rich nanocomposite. The crystallinity of the nanostructure was investigated using X-ray diffraction. A scanning electron microscope (SEM) was used to examine the surface morphology, revealing hexagonal nanoparticles with an average particle size of 400 nm. High-resolution transmission electron microscopy (HR-TEM) was used to confirm the nanostructure of the doped material. The nanostructure's bonding and functional groups were verified using Fourier transform infrared spectroscopy (FTIR). The electrochemical characterization was conducted by using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and amperometry. The resistivity of the electrode was confirmed through EIS and showed that the bare glassy carbon electrode (GCE) exhibited higher charge transfer resistance as compared to modified Zn-Co2O4/GCE. The sensing probe was developed by modifying the surface of GCE with Zn-Co2O4 nanostructure and tested as an electrochemical sensor for dopamine oxidation; it operated best at a working potential of 0.17 V (vs Ag/AgCl). The developed sensor exhibited a low limit of detection (0.002 µM), a high sensitivity (126 µA. µM-1 cm-2), and a wide linear range (0.2 to 185 µM). The sensor showed a short response time of < 1 s. The sensor's selectivity was investigated in the presence of coexisting species (uric acid, ascorbic acid, adrenaline, epinephrine, norepinephrine, histamine, serotonin, tyramine, phenethylamine, and glucose) with no effects on dopamine determination results. The developed sensor was also successfully used for determining dopamine concentrations in a real sample.

Transcriptional regulators and regulatory pathways involved in prostate gland adaptation to a hypoandrogen environment.

Anti-androgen therapies, including orchiectomy, are effective at promoting prostate cancer remission, but are followed by progression to the more aggressive castration-resistant prostate cancer (CRPC). Castration promotes gland and tumor shrinkage. However, prostate adaptation to androgen deprivation involves striking parallel events, all requiring changes in gene expression. We hypothesized that transcription factors (TF) and other transcription-related genes are needed to orchestrate those changes. In this work, downstream analysis using bioinformatic tools and published microarray data allowed us to identify sixty transcriptional regulators (including 10 TF) and to integrate their function in physiologically relevant networks. Functional associations revealed a connection between Arnt, Bhlhe41 and Dbp circadian rhythm genes with the Ar circuitry and a small gene network centered in Pex14, which might indicate a previously unanticipated metabolic shift. We have also identified human homologs and mapped the corresponding genes to human chromosome regions commonly affected in prostate cancer, with particular attention to the PTEN/HHEX/MXI1 cluster at 10q23-25 (frequently deleted in PCa) and to MAPK1 at 22q11.21 (delete in intermediate risk but not in high risk PCa). Twenty genes were found mutated or with copy number alterations in at least five percent of three cancer cohorts and six of them (PHOX2A, NFYC, EST2, EIF2S1, SSRP1 and PARP1) associated with impacted patient survival. These changes are specific to the adaptation to the hypoandrogen environment and seem important for the progression to CRPC when mutated.

Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1142 -macrophages.

Prostate development and function are regulated by androgens. Epithelial cell apoptosis in response to androgen deprivation is caspase-9-dependent and peaks at Day 3 after castration. However, isolated epithelial cells survive in the absence of androgens. Znf142 showed an on-off expression pattern in intraepithelial CD68-positive macrophages, with the on-phase at Day 3 after castration. Rats treated with gadolinium chloride to deplete macrophages showed a significant drop in apoptosis, suggesting a causal relationship between macrophages and epithelial cell apoptosis. Intraepithelial M1-polarization was also limited to Day 3, and the inducible nitric oxide synthase (iNOS) knockout mice showed significantly less apoptosis than wild-type controls. The epithelial cells showed focal DNA double-strand breaks (DSB), 8-oxoguanine, and protein tyrosine-nitrosylation, fingerprints of exposure to peroxinitrite. Cultured epithelial cells induced M1-polarization and showed focal DSB and underwent apoptosis. The same phenomena were reproduced in LNCaP cells cocultured with Raw 264.7 macrophages. In conclusion, the M1 142 -macrophage (named after Znf142) attack causes activation of the intrinsic apoptosis pathway in epithelial cells after castration.

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases.

In vitro antibacterial activity of selected medicinal plants from lower Himalayas.

The present studies cover antibacterial activity of the crude methanolic extracts of 11 medicinal plants viz. Adhatoda vasica, Bauhenia variegate, Bombax ceiba, Carrisa opaca, Caryopteris grata, Debregeasia salicifolia, Lantana camara, Melia azedarach, Phyllanthus emblica, Pinus roxburghii and Olea ferruginea collected from lower Himalayas against two Gram positive (Staphylococcus aureus, Micrococcus luteus) and two Gram negative (Escherichia coli, Pseudomonas aureginosa) bacterial strains. The extracts were applied at four different concentrations (120 mg/mL, 90mg/mL, 60mg/mL and 30mg/mL) in dimethyl sulfoxide (DMSO) by using agar well diffusion method. Antibacterial activities against Staphylococcus aureus and Micrococcus luteus were observed formethanolic extracts of all the above mentioned plants. Greater antibacterial activity against Pseudomonas aeruginosa was only exhibited by Phyllanthus emblica, Pinus roxburghii, Debregeasia salicifolia and Lantana camara. Escherichia coli was highly resistant to all the plant extracts at all concentrations. It is inferred that methanolic crude extracts of the above mentioned plantsexhibitantibacterial activities against pathogenic bacteria, which proved the ethnobotanical importance of the selected plants that indigenous people use for cure against various diseases.

Uric acid quantification via colorimetric detection utilizing silver oxide-modified activated carbon nanoparticles functionalized with ionic liquid.

Uric acid (UA) is a significant indicator of human health because it is linked to several diseases, including renal failure, kidney stones, arthritis, and gout. Uric acid buildup in the joints is the source of chronic and painful diseases. When UA is present in large quantities, it causes tissue injury in the joints that are afflicted. In this research, silver oxide-doped activated carbon nanoparticles were synthesized and then functionalized with an ionic liquid. The synthesized nanomaterial assembly was employed as a colorimetric sensing platform for uric acid. Activated carbon offers a large internal surface area that acts as a good carrier for catalytic reactions. A salt-melting approach was used to synthesize the silver oxide-doped activated carbon nanocomposite. The synthesis was confirmed through various techniques, such as UV-vis spectrophotometer, FTIR, XRD, SEM, and EDX. The colorimetric change from blue-green to colorless was observed with the naked eye and confirmed by UV-vis spectroscopy. To obtain the best colorimetric change, several parameters, such as pH, capped NP loading, TMB concentration, hydrogen peroxide concentration, and time, were optimized. The optimized experimental conditions for the proposed sensor were pH 4 with 35 µL of NPs, a 40 mM TMB concentration, and a 4 minutes incubation time. The sensor linear range is 0.001-0.36 µM, with an R2 value of 0.999. The suggested sensor limits of detection and quantification are 0.207 and 0.69 nM, respectively. Potential interferers, such as ethanol, methanol, urea, Ca2+, K+, and dopamine, did not affect the detection of uric acid.

In-silico evaluation of natural alkaloids against the main protease and spike glycoprotein as potential therapeutic agents for SARS-CoV-2.

Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has resulted in global fatalities since late December 2019. Alkaloids play a significant role in drug design for various antiviral diseases, which makes them viable candidates for treating COVID-19. To identify potential antiviral agents, 102 known alkaloids were subjected to docking studies against the two key targets of SARS-CoV-2, namely the spike glycoprotein and main protease. The spike glycoprotein is vital for mediating viral entry into host cells, and main protease plays a crucial role in viral replication; therefore, they serve as compelling targets for therapeutic intervention in combating the disease. From the selection of alkaloids, the top 6 dual inhibitory compounds, namely liensinine, neferine, isoliensinine, fangchinoline, emetine, and acrimarine F, emerged as lead compounds with favorable docked scores. Interestingly, most of them shared the bisbenzylisoquinoline alkaloid framework and belong to Nelumbo nucifera, commonly known as the lotus plant. Docking analysis was conducted by considering the key active site residues of the selected proteins. The stability of the top three ligands with the receptor proteins was further validated through dynamic simulation analysis. The leads underwent ADMET profiling, bioactivity score analysis, and evaluation of drug-likeness and physicochemical properties. Neferine demonstrated a particularly strong affinity for binding, with a docking score of -7.5025 kcal/mol for main protease and -10.0245 kcal/mol for spike glycoprotein, and therefore a strong interaction with both target proteins. Of the lead alkaloids, emetine and fangchinoline demonstrated the lowest toxicity and high LD50 values. These top alkaloids, may support the body's defense and reduce the symptoms by their numerous biological potentials, even though some properties naturally point to their direct antiviral nature. These findings demonstrate the promising anti-COVID-19 properties of the six selected alkaloids, making them potential candidates for drug design. This study will be beneficial in effective drug discovery and design against COVID-19 with negligible side effects.

Colorimetric sensing of hydrogen peroxide using capped Morus nigra-sawdust deposited zinc oxide nanoparticles via Trigonella foenum extract.

Hydrogen peroxide (H2O2) is one of the main byproducts of most enzymatic reactions, and its detection is very important in disease conditions. Due to its essential role in healthcare, the food industry, and environmental research, accurate H2O2 determination is a prerequisite. In the present work, Morus nigra sawdust deposited zinc oxide (ZnO) nanoparticles (NPs) were synthesized by the use of Trigonella foenum extract via a hydrothermal process. The synthesized platform was characterized by various techniques, including UV-Vis, FTIR, XRD, SEM, EDX, etc. FTIR confirmed the presence of a Zn‒O characteristic peak, and XRD showed the hexagonal phase of ZnO NPs with a 35 nm particle size. The EDX analysis confirmed the presence of Zn and O. SEM images showed that the as-prepared nanoparticles are distributed uniformly on the surface of sawdust. The proposed platform (acetic acid-capped ZnO NPs deposited sawdust) functions as a mimic enzyme for the detection of H2O2 in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) colorimetrically. To get the best results, many key parameters, such as the amount of sawdust-deposited nanoparticles, TMB concentration, pH, and incubation time were optimized. With a linear range of 0.001-0.360 µM and an R2 value of 0.999, the proposed biosensor's 0.81 nM limit of quantification (LOQ) and 0.24 nM limit of detection (LOD) were predicted, respectively. The best response for the proposed biosensor was observed at pH 7, room temperature, and 5 min of incubation time. The acetic acid-capped sawdust deposited ZnO NPs biosensor was also used to detect H2O2 in blood serum samples of diabetic patients and suggest a suitable candidate for in vitro diagnostics and commercial purposes.

From waste to wealth: iron oxide doped hydroxyapatite-based biosensor for the colorimetric detection of ascorbic acid.

Ascorbic acid plays a pivotal role in the human body. It maintains the robustness, enlargement, and elasticity of the collagen triple helix. However, the abnormal concentration of ascorbic acid causes various diseases, such as scurvy, cardiovascular diseases, gingival bleeding, urinary stones, diarrhea, stomach convulsions, etc. In the present work, an iron-doped hydroxyapatite (HAp@Fe2O3)-based biosensor was developed for the colorimetric detection of ascorbic acid based on a low-cost, biocompatible, and ubiquitous material. Due to the catalytic nature of HAp owing to the acidic and basic moieties within the structure, it was used as a template for HAp@Fe2O3 synthesis. This approach provides an active as well as large surface area for the sensing of ascorbic acid. The synthesized platform was characterized by various techniques, such as UV-Vis, FTIR, SEM, XRD, TGA, EDX, etc. The HAp@Fe2O3 demonstrated inherent peroxidase-like activity in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) oxidized with the assistance of H2O2. It resulted in the color changing to blue-green, and after the addition of ascorbic acid, the color changed to colorless, resulting in the reduction of TMB. To achieve optimal sensing parameters, experimental conditions were optimized. The quantity of HAp@Fe2O3, H2O2, pH, TMB, time, and the concentration of ascorbic acid were fine-tuned. The linear range for the proposed sensor was 0.6-56 µM, along with a limit of detection of 0.16 µM and a limit of quantification of 0.53 µM. The proposed sensor detects ascorbic acid within 75 seconds at room temperature. The proposed platform was also applied to quantitatively check the concentration of ascorbic acid in a physiological solution.

Hymenaea courbaril resin-mediated gold nanoparticles as catalysts in organic dyes degradation and sensors in pharmaceutical pollutants.

In this study, green synthesis of gold nanoparticles (AuNPs) using aqueous extract from Hymenaea courbaril resin (HCR) is reported. The successful formation, functional group involvement, size, and morphology of the subject H. courbaril resin mediated gold nanoparticles (HCRAuNPs) were confirmed by Ultra Violet-Visible (UV-vis) spectroscopy, Fourier-Transform Infrared spectroscopy (FTIR), and Transmission Electron Microscopy (TEM) techniques. Stable and high yield of HCRAuNPs was formed in 1:15 (aqueous solution: salt solution) reacted in sunlight as indicated by the visual colour change and appearance of surface Plasmon resonance (SPR) at 560 nm. From the FT-IR results, the phenolic hydroxyl (-OH) functional group was found to be involved in synthesis and stabilization of nanoparticles. The TEM analysis showed that the particles are highly dispersed and spherical in shape with average size of 17.5 nm. The synthesized HCRAuNPs showed significant degradation potential against organic dyes, including methylene blue (MB, 85 %), methyl orange (MO, 90 %), congo red (CR, 83 %), and para nitrophenol (PNP, 76 %) up to 180 min. The nanoparticles also demonstrated the effective detection of pharmaceutical pollutants, including amoxicillin, levofloxacin, and azithromycin in aqueous environment as observable changes in color and UV-Vis spectral graph.

Identification of Novel Quinolone and Quinazoline Alkaloids as Phosphodiesterase 10A Inhibitors for Parkinson's Disease through a Computational Approach.

Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson's disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A. This study involved detailed in silico evaluations through docking followed by pharmacological, pharmacophoric, and pharmacokinetic analyses, prioritizing central nervous system (CNS)-active drug criteria. Seven cyclic peptides, those featuring the quinazoline/quinazoline moiety at both termini, exhibited notably enhanced docking scores compared to those of the remaining alkaloids within the screened library. We identified 7 quinolines and 1 quinazoline including Lepadin G, Aspernigerin, CJ-13536, Aurachin A, 2-Undecyl-4(1H)-quinolone, Huajiaosimuline 3-Prenyl-4-prenyloxyquinolin-2-one, and Isaindigotone that followed the standard CNS active drug criteria. The dominant quinoline ring in our study and its related quinazoline were central to our evaluations; therefore, the pharmacophoric features of these scaffolds were highlighted. The top alkaloids met all CNS-active drug properties; while nonmutagenic and without PAINS alerts, many indicated potential hepatotoxicity. Among the compounds, Huajiaosimuline was particularly significant due to its alignment with lead-likeness and CNS-active criteria. Aspernigerin demonstrated its affinity for numerous dopamine receptors, which signifies its potential to alter dopaminergic neurotransmission that is directly related to PD. Interestingly, the majority of these alkaloids had biological targets primarily associated with G protein-coupled receptors, critical in PD pathophysiology. They exhibit superior excretion parameters and toxicity end-points compared to the standard. Notably, selected alkaloids demonstrated stability in the binding pocket of PDE10A according to the molecular dynamic simulation results. Our findings emphasize the potential of these alkaloids as PDE10A inhibitors. Further experimental studies may be necessary to confirm their actual potency in inhibiting PDE10A before exploring their therapeutic potential in PD.

Nanozyme-based sensing of dopamine using cobalt-doped hydroxyapatite nanocomposite from waste bones.

Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.

Modulation in serum and hematological parameters as a prognostic indicator of COVID-19 infection in hypertension, diabetes mellitus, and different cardiovascular diseases.

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.

Decrypting the multi-genome data for chimeric vaccine designing against the antibiotic resistant Yersinia pestis.

Yersinia pestis, the causative agent of plague, is a gram-negative bacterium that can be fatal if not treated properly. Three types of plague are currently known: bubonic, septicemic, and pneumonic plague, among which the fatality rate of septicemic and pneumonic plague is very high. Bubonic plague can be treated, but only if antibiotics are used at the initial stage of the infection. But unfortunately, Y. pestis has also shown resistance to certain antibiotics such as kanamycin, minocycline, tetracycline, streptomycin, sulfonamides, spectinomycin, and chloramphenicol. Despite tremendous progress in vaccine development against Y. pestis, there is no proper FDA-approved vaccine available to protect people from its infections. Therefore, effective broad-spectrum vaccine development against Y. pestis is indispensable. In this study, vaccinomics-assisted immunoinformatics techniques were used to find possible vaccine candidates by utilizing the core proteome prepared from 58 complete genomes of Y. pestis. Human non-homologous, pathogen-essential, virulent, and extracellular and membrane proteins are potential vaccine targets. Two antigenic proteins were prioritized for the prediction of lead epitopes by utilizing reverse vaccinology approaches. Four vaccine designs were formulated using the selected B- and T-cell epitopes coupled with appropriate linkers and adjuvant sequences capable of inducing potent immune responses. The HLA allele population coverage of the T-cell epitopes selected for vaccine construction was also analyzed. The V2 constructs were top-ranked and selected for further analysis on the basis of immunological, physicochemical, and immune-receptor docking interactions and scores. Docking and molecular dynamic simulations confirmed the stability of construct V2 interactions with the host immune receptors. Immune simulation analysis anticipated the strong immune profile of the prioritized construct. In silico restriction cloning ensured the feasible cloning ability of the V2 construct in the expression system of E. coli strain K12. It is anticipated that the designed vaccine construct may be safe, effective, and able to elicit strong immune responses against Y. pestis infections and may, therefore, merit investigation using in vitro and in vivo assays.

Mechanical properties, and in vitro biocompatibility assessment of biomimetic dual layered keratin/ hydroxyapatite scaffolds.

A novel biomimetic dual layered keratin/hydroxyapatite (keratin/HA) scaffold was designed using iterative freeze-drying technique. The prepared scaffolds were studied using several analytical techniques to better understand the biological, structural, and mechanical properties. The developed multilayered, interconnected, porous keratin scaffold with different hydroxyapatite (HA) content in the outer and inner layer, mimics the inherent gradient structure of alveolar bone. SEM studies showed an interconnected porous architecture of the prepared scaffolds with seamless integration between the upper and lower layers. The incorporation of HA improved the mechanical properties keratin/HA scaffolds. The keratin/HA scaffolds exhibited superior mechanical properties in terms of Young's modulus and compressive strength in comparison to pure keratin scaffolds. The biocompatibility studies suggested that both keratin and keratin/HA scaffolds were cyto-compatible, in terms of cell proliferation. Furthermore, it showed that both the tested materials can served as an ideal substrate for the differentiation of Saos-2 cells, leading to mineralization of the extracellular matrix. In summary, ionic liquid based green technique was employed for keratin extraction to fabricate keratin/HA scaffolds and our detailed in vitro investigations suggest the great potential for these composite scaffolds for bone tissue engineering in future.

Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets.

Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.

Computer-aided identification of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) inhibitors from Gymnema sylvestre natural products.

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world's population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre.