Cell permeability was evaluated by measuring movements of FITC-dextran. A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins. The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.Mutations in human genes might lead to loss of functional proteins, causing diseases. Among these genetic disorders, a large class is associated with the deficiency in metabolic enzymes, resulting in both an increase in the concentration of substrates and a loss in the metabolites produced by the catalyzed reactions. The identification of therapeutic actions based on small molecules represents a challenge to medicinal chemists because the target is missing. click here Alternative approaches are biology-based, ranging from gene and stem cell therapy, CRISPR/Cas9 technology, distinct types of RNAs, and enzyme replacement therapy (ERT). This review will focus on the latter approach that since the 1990s has been successfully applied to cure many rare diseases, most of them being lysosomal storage diseases or metabolic diseases. So far, a dozen enzymes have been approved by FDA/EMA for lysosome storage disorders and only a few for metabolic diseases. Enzymes for replacement therapy are mainly produced in mammalian cells and some in plant cells and yeasts and are further processed to obtain active, highly bioavailable, less degradable products. Issues still under investigation for the increase in ERT efficacy are the optimization of enzymes interaction with cell membrane and internalization, the reduction in immunogenicity, and the overcoming of blood-brain barrier limitations when neuronal cells need to be targeted. Overall, ERT has demonstrated its efficacy and safety in the treatment of many genetic rare diseases, both saving newborn lives and improving patients' life quality, and represents a very successful example of targeted biologics. This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CI-AKI). Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription-polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal-deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.Due to its fast international spread and substantial mortality, the coronavirus disease COVID-19 evolved to a global threat. Since currently, there is no causative drug against this viral infection available, science is striving for new drugs and approaches to treat the new disease. Studies have shown that the cell entry of coronaviruses into host cells takes place through the binding of the viral spike (S) protein to cell receptors. Priming of the S protein occurs via hydrolysis by different host proteases. The inhibition of these proteases could impair the processing of the S protein, thereby affecting the interaction with the host-cell receptors and preventing virus cell entry. Hence, inhibition of these proteases could be a promising strategy for treatment against SARS-CoV-2. In this review, we discuss the current state of the art of developing inhibitors against the entry proteases furin, the transmembrane serine protease type-II (TMPRSS2), trypsin, and cathepsin L.We provide a brief review of the significance of platelets, mitochondria, vitamin D, serotonin and the gutmicrobiome in COVID-19. We hypothesize that hyperactive platelets and mitochondrial dysfunction, as well as low vitamin D level, gut dysbiosis and increased serum serotonin produced by enterochromaffin cells, may all represent important aspects in the pathophysiology of COVID-19. Peptides and peptide-based therapeutics are biomolecules that demarcate a significant chemical space to bridge small molecules with biological therapeutics such as antibodies, recombinant proteins, and protein domains. Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived thiazoline-based cyclopolypeptides (CTBCs), exhibit a wide array of pharmacological activities due to their unique structural features and interesting bioactions, which furnish them as promising leads for drug discovery. In the present study, we comprehensively review the natural sources, distinguishing chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities counting the mode of actions for biological portrayals which render CTBCs as indispensable sources for the emergence of prospective peptide-based therapeutics. In this milieu, metal organic frameworks and their biomedical applications are also briefly discussed. To boot, the challenges, approaches, and clinical status of peptide-based therapeutics are conferred.