While the world is still attempting to recover from the damage caused by the broad spread of COVID-19, the monkeypox virus poses a new threat of becoming a global pandemic. Although the Monkeypox virus itself is not deadly and contagious as COVID-19, still every day, new patients case has been reported from many nations. Therefore, it will be no surprise if the world ever faces another global pandemic due to the lack of proper precautious steps. Recently, Machine learning (ML) has demonstrated huge potential in image-based diagnoses such as cancer detection, tumor cell identification, and COVID-19 patient detection. Therefore, a similar application can be adopted to diagnose the Monkeypox related disease as it infected the human skin, which image can be acquired and further used in diagnosing the disease. However, there is no publicly available Monkeypox dataset that can be used for training and experimenting the ML model development. Consequently, there is an immediate need to develop a dataset containing Monkeypox infected patients' images. Considering this opportunity, in this work, we introduce a newly developed "Monkeypox2022" dataset that is publicly available to use and can be obtained from our shared GitHub repository. The dataset is created by collecting images from multiple open-source and online portals that do not impose any restrictions on use, even for commercial purposes, hence giving a safer path to use and disseminate such data when constructing and deploying any type of ML models. Further, we propose and evaluate a modified VGG16 model, which includes two distinct studies: Study One and Two. Our exploratory computational results indicate that our suggested model can identify Monkeypox patients with an accuracy of 97 ± 1.8% (AUC = 97.2) and 88 ± 0.8% ( AUC = 0.867) for Study One and Two, respectively. Additionally, we explain our model's prediction and feature extraction utilizing Local

Antibiotic resistance poses an immediate and growing threat to human health. Multidrug efflux pumps are promising targets for overcoming antibiotic resistance with small-molecule therapeutics. Previously, we identified a diaminoquinoline acrylamide, NSC-33353, as a potent inhibitor of the AcrAB− TolC efflux pump in Escherichia coli. This inhibitor potentiates the antibacterial activities of novobiocin and erythromycin upon binding to the membrane fusion protein AcrA. It is also a substrate for efflux and lacks appreciable intrinsic antibacterial activity of its own in wild-type cells. Here, we have modified the substituents of the cinnamoyl group of NSC-33353, giving rise to analogs that retain the ability to inhibit efflux, lost the features of the efflux substrates, and gained antibacterial activity in wild-type cells. The replacement of the cinnamoyl group with naphthyl isosteres generated compounds that lack antibacterial activity but are both excellent efflux pump inhibitors and substrates. Surprisingly, these inhibitors potentiate the antibacterial activity of novobiocin but not erythromycin. Surface plasmon resonance experiments and molecular docking suggest that the replacement of the cinnamoyl group with naphthyl shifts the affinity of the compounds away from AcrA to the AcrB transporter, making them better efflux substrates and changing their mechanism of inhibition. These results provide new insights into the duality of efflux substrate/inhibitor features in chemical scaffolds that will facilitate the development of new efflux pump inhibitors.

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Optimization of compound permeation into Gram-negative bacteria is one of the most challenging tasks in the development of antibacterial agents. Two permeability barriers�the passive diffusion barrier of the outer membrane (OM) and active drug efflux�act synergistically to protect cells from the antibacterial action of compounds. In Escherichia coli (E. coli) and relatives, these two barriers sieve compounds based on different physicochemical properties that are defined by their interactions with OM porins and efflux pumps, respectively. In this study, we critically tested the hypothesis that the best substrates and inhibitors of efflux pumps are compounds that can effectively permeate the OM and are available at relatively high concentrations in the periplasm. For this purpose, we filtered a large subset of the ZINC15 database of commercially available compounds for compounds containing a primary amine, a chemical feature known to facilitate the uptake through E. coli general porins. The assembled library was screened by ensemble docking to AcrA, the periplasmic component of the AcrAB-TolC efflux pump, followed by experimental testing of the top predicted binders for antibacterial activities, efflux recognition, and inhibition. We found that the filtered primary amine library is a rich source of compounds with effluxinhibiting activities and identified efflux pump inhibitors with novel chemical scaffolds effective against E. coli AcrAB-TolC and efflux pumps of multidrug-resistant clinical isolates of Acinetobacter baumannii. However, primary amines are not required for the recognition of compounds by efflux pumps and their efflux-inhibitory activities.

Both acute and chronic kidney diseases substantially contribute to the morbidities and mortality of patients worldwide. The existing therapeutics, which are mostly developed from synthetic sources, present some unexpected effects in patients, provoking researchers to explore potential novel alternatives. Natural products that have protective effects against various renal pathologies could be potential drug candidates for kidney diseases. Mangiferin is a natural polyphenol predominantly isolated from Mangifera indica and possesses multiple health benefits against various human ailments, including kidney disease. The main objective of this review is to update the renoprotective potentials of mangiferin with underlying molecular pharmacology and to highlight the recent development of mangiferin-based therapeutics toward kidney problems. Literature published over the past decade suggests that treatment with mangiferin attenuates renal inflammation and oxidative stress, improves interstitial fibrosis and renal dysfunction, and ameliorates structural alteration in the kidney. Therefore, mangiferin could be used as a multi-target therapeutic candidate to treat renal diseases. Although mangiferin-loaded nanoparticles have shown therapeutic promise against various human diseases, there is limited information on the targeted delivery of mangiferin in the kidney. Further research is required to gain insight into the molecular pharmacology of mangiferin targeting kidney diseases and translate the preclinical results into clinical use.

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BackgroundHuman health is largely affected by self-medication in both ways, adversely and favorably, as evidenced by the COVID-19 pandemic. The fear of spreading COVID-19 among health workers and hospital environments has led many Bangladeshi people to practice self-medicate for as a preventive strategy against this disease. Consequently, this practice entails an improper and injudicious use of medicine to cure self-recognized symptoms. To date, the COVID-19 has no effective treatment. The lack of a cure for COVID-19 and the continual progression of the diseases in educational settings induce a substantial population to practice self-medication. Therefore a study of self-medication practices is necessary for the framework of the pandemic. This study aimed to estimate the prevalence and factors associated with self-medication to prevent or manage future COVID-19 infections among recovered COVID-19 patients.MethodsThis cross-sectional study was conducted from September 2020 to February 2021 using an e-survey along with 360 participants. Data were collected using a pre-tested self-reported questionnaire. Descriptive statistics and correlations analysis were performed in the study.ResultsAmong 360 participants, males were 69.7%, and females 30.3%. The prevalence of self-medication is 11%, and monthly family income, residence, education, occupation, and previous history of SM are the associated factors. Among the participants, 29.7% use antibiotics, and 30% use herbal products or drugs as medication.ConclusionThe present study found SMP is moderately prevalent among COVID-19 recovered patients. To minimize the rate of SMP, adequate health care access systems and public education should be introduced, and media & community should be engaged in rational use of medication.