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Diabetes is emerging as an epidemic and is becoming a public health concern worldwide. Diabetic nephropathy is one of the serious complications of diabetes, and about 40% of individuals with diabetes develop diabetic nephropathy. The consistent feature of diabetes and its associated nephropathy is hyperglycemia, and in some cases, hyperamylinemia. Currently, the treatment includes the use of medication for blood pressure control, sugar control, and cholesterol control, and in the later stage requires dialysis and kidney transplantation, making the management of this complication very difficult. Bioactive compounds, herbal medicines, and extracts are extensively used in the treatment and prevention of several diseases, and some are reported to be efficacious in diabetes too. Therefore, in this study, we tried to identify the therapeutic potential of phytochemicals used in in silico docking and molecular dynamic simulation studies using a library of 5284 phytochemicals against the two potential targets of type 2 diabetes-associated nephropathy. We identified two phytochemicals (i.e., gentisic acid and michelalbine) that target human amylin peptide and dipeptidyl peptidase-4, respectively, with good binding affinity. These phytochemicals can be further evaluated using in vitro and in vivo studies for their anti-hyperglycemia and anti-hyperamylinemia effects. [ABSTRACT FROM AUTHOR]

To the Editor, The current worldwide coronavirus sickness outbreak is caused by a new coronavirus structurally connected to the virus that causes severe acute respiratory syndrome (SARS), known as (COVID-19). Indeed, since COVID-19 (SARSCoV2) was discovered in Wuhan, Hubei Province, China in December 2019, healthcare systems throughout the world have faced huge challenges.[1] Hypertension, which is common in people all over the world, has been recognized as a key risk factor for higher COVID-19 severity. Hypertension is still a moving target in the context of COVID-19 and post-acute COVID-19 syndrome. [Extracted from the article]

Keywords: COVID-19; vaccines; S protein; neutralizing antibodies; two proline substitutions EN COVID-19 vaccines S protein neutralizing antibodies two proline substitutions 769 772 4 09/04/21 20210701 NES 210701 The spike protein of SARS-CoV-2 is the first target identified by researchers on COVID-19 vaccines. Consequently, an efficient way of enhancing the effectiveness of S protein vaccines is by stabilizing the pre-fusion conformation of the S protein. Moreover, T cells targeting the S protein have been identified in SARS-CoV, MERS-CoV, and SARS-CoV-2. Some studies reported that the S-2P expression in the Ad26 vaccine from Janssen induces high levels of nAbs and is safer than the other native S protein vaccines in NHPs [[19]]. [Extracted from the article]

Keywords: COVID-19; vaccines; T cell; adenovirus vector; lipid nanoparticle EN COVID-19 vaccines T cell adenovirus vector lipid nanoparticle 5 7 3 01/20/22 20220101 NES 220101 B Abbreviations b : LNP: lipid nanoparticle; AdV: adenovirus vector; DCs: dendritic cells; PKR: dsRNA-dependent kinase; TLR: Toll-like receptors The fast approval of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a result of the development of vaccine technologies in the last several years. Comparison of neutralizing antibody responses against SARS-CoV-2 in healthy volunteers who received the BNT162b2 mRNA or the AZD1222 vaccine: should the second AZD1222 vaccine dose be given earlier? Hence, a new vaccine that can be taken through inhalation and can stimulate tissue-resident memory T cells in the lung, which are formed at the initial infection, may be produced using mRNA vaccines because they can self-replicate (imitate viral replication) [[15]]. [Extracted from the article]

Antifibrotic drug combinations are likely to target many orthogonal pathways, comprising a variety of receptors, signaling, and types of cells that have been shown to act in multiple disease states as key drivers of fibrosis. Dear Editor, Fibrosis is described as the overgrowth, hardness, and/or scarring of different tissues caused by an excess of extracellular matrix components such as collagen. As observed in intestinal and liver fibrosis, the last stage for fibrosis clinical trials proceed to develop and can involve a global approach involving patients, researchers, scientists, business leaders, and regulatory partners. [Extracted from the article]

Food and Drug Administration (FDA) and the European Medicines Agency (EMA) were approved the only topical minoxidil and oral finasteride as treatment for androgenetic alopecia. Finasteride is made to prohibit the conversion of testosterone to Dihydrotestosterone (DHT) through inhibition of the testosterone 5 -reductase enzyme. Caserini, M. Radicioni, C. Leuratti, Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia. [Extracted from the article]

The infiltration of immune cells is a hallmark of most forms of malignancy. It is well known that in Tumor Microenvironment (TME), monocytes undergo reprogramming process to differentiate into Tumor Associated Macrophages (TAMs) (M2 macrophages). Interestingly, this reprogramming process depends on signals provided by tumors. Hence, tumors from several tissues are infiltrated by functionally distinct TAMs populations. Tumor Protein p53(TP53) plays a role in the regulation or progression of DNA damage and repair through multiple mechanisms of the cell cycle, apoptosis, and genomic stability. Although, TP53 acts as a physiological break for M2 macrophages polarization; the potential regulatory function of TP53 in the infiltration of macrophages is still unknown. We used the Cancer Genomic Atlas (TCGA) clinical data from 10,009 samples across 30 types of cancer via the Tumor IMmune Estimation Tool (TIMER) (https://cistrome.shinyapps.io/timer/) to investigate whether TP53 status has an important clinical outcome on macrophages infiltration in different cancer types. Our analysis of TCGA showed that Ovarian Serous Cystadenocarcinoma (OV) patients with mutant TP53 had significantly higher macrophages infiltration than those with wild-type TP53 (P-value < 0.05) and poor prognosis associated. In contrast, Stomach Adenocarcinoma (STAD) patients with wild-type TP53 had considerably higher macrophages infiltration than those with mutant TP53 (P-value < 0.01) and poor clinical outcomes. Herein, our study sheds light on the novel clinical role of TP53 in macrophages infiltration in TME of OV and STAD patients. Furthermore, the modulation of TP53 and its co-regulators may serve as promising targets for OV and STAD patients. [ABSTRACT FROM AUTHOR]

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic cancer. Emerging evidence suggests that tumor-associated macrophages (TAMs) play an immunosuppressive role in the tumor microenvironment and promote tumor growth, angiogenesis, and metastasis in ovarian cancer. Therefore, targeting TAMs in patients with ovarian cancer is an appealing strategy; however, all trials to date have failed. To improve the efficacy of this approach, we sought to elucidate the underlying mechanisms of the role of TAMs in ovarian cancer. We found that the developmental transcription factor GATA3 was highly expressed in HGSOC cell lines but not in the fallopian tube, which is the main origin of HGSOC. GATA3 expression was associated with poor prognosis in HGSOC patients (P <.05) and was found to promote proliferation and migration in HGSOC cell lines. GATA3 was released abundantly from TAM cells via exosomes and contributed to tumor growth in the tumor microenvironment. Moreover, GATA3 acted as a regulator for macrophage polarization and interactions between TAMs and HGSOC to support proliferation, motility, and cisplatin chemoresistance in mutant TP53 HGSOC cell lines. Furthermore, GATA3 played a critical role in the interactions between TAMs and mutant TP53 HGSOC to promote angiogenesis and epithelial-mesenchymal transition with epigenetic regulation. Targeting GATA3 using GATA3siRNA in TAMs impeded GATA3-driven proliferation, migration, cisplatin chemoresistance, and angiogenesis in mutant TP53 HGSOC cell lines. Our findings indicate that GATA3 plays a novel role in immunoediting of HGSOC and demonstrate that GATA3 may serve as a prognostic marker for HGSOC and a promising target in the treatment of HGSOC. Unlabelled Image • Expression of TAMs markers is often associated with poor clinical outcome in HGSOC patients. • GATA3 is highly expressed in HGSOC patients but not in the fallopian tube, the main origin of HGSOC. • GATA3 act as oncogenic protein in HGSOC patients. • GATA3 was released abundantly from TAM cells via exosomes and contributed to tumor growth in the tumor microenvironment. • GATA3 is a master regulator for macrophage polarization and interactions between TAMs and HGSOC. • TAMs-Exosomal-GATA3 was supported proliferation, motility, angiogenesis and cisplatin-chemoresistance in mutant-TP53 HGSOC. • GATA3 plays a novel role in immuno-editing of HGSOC. • GATA3 is a promising target to eradicate HGSOC in the future. • GATA3 acted as tumor suppressor in endometrial cancer. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Comment on: Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in male rats," by Amr Ahmed El-Arabey in the 2016 issue.

A letter to the editor is presented in response to the article "Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats" by S. Jilanchi and colleagues in a previous issue.

The transmembrane glycoprotein angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS). It was shown to be the receptor of severe acute respiratory syndrome coronavirus 2 in the COVID-19 outbreak (SARS-COV-2). Furthermore, ACE2 aids in the transport of amino acids across the membrane. ACE2 is lost from the membrane, resulting in soluble ACE2 (sACE2). We aim to examine the structural conformation alterations between SARS-CoV-1 or 2 variants at various periods with ACE2 from various sources, particularly in the area where it interacts with the viral protein and the receptor. It is important to study the molecular dynamics of ACE2/SARS-COV RBD when the structure is available on the database. Here we analyzed the crystal structure of ACE2 from Human, Dog, Mus, Cat, and Bat ACE2 in complex with RBD from SARS-COV-1 and SARS-COV-2. The result shows, there is a variation in the type of residues, number of contact atoms and hydrogen bonds in ACE2 and RBD during the interaction interfaces. By using molecular dynamics simulation, we can measure RMSD, RMSF, SASA, Rg and the difference in the percentage of α helix and β strand. As bat ACE2 & SARS-CoV-2 RBD found to have a high amount of β strand compared to another structure complex, while hACE2 & SARS-CoV-1 RBD has fewer amounts of β strand. Our study provides a deep view of the structure which is available and a summary of many works around ACE2/SARS-CoV RBD interaction.Communicated by Ramaswamy H. Sarma.

The SARS-CoV-2 infection activates host kinases and causes high phosphorylation in both the host and the virus. There were around 70 phosphorylation sites found in SARS-CoV-2 viral proteins. Besides, almost 15,000 host phosphorylation sites were found in SARS-CoV-2-infected cells. COVID-19 is thought to enter cells via the well-known receptor Angiotensin-Converting Enzyme 2 (ACE2) and the serine protease TMPRSS2. Substantially, the COVID-19 infection doesn't induce phosphorylation of the ACE2 receptor at Serin-680(s680). Metformin's numerous pleiotropic properties and extensive use in medicine including COVID-19, have inspired experts to call it the "aspirin of the twenty-first century". Metformin's impact on COVID-19 has been verified in clinical investigations via ACE2 receptor phosphorylation at s680. In the infection of COVID-19, sodium-dependent transporters including the major neutral amino acid (B 0 AT1) is regulated by ACE2. The structure of B 0 AT1 complexing with the COVID-19 receptor ACE2 enabled significant progress in the creation of mRNA vaccines. We aimed to study the impact of the interaction of the phosphorylation form of ACE2-s680 with wild-type (WT) and different mutations of SARS-CoV-2 infection such as delta, omicron, and gamma (γ) on their entrance of host cells as well as the regulation of B 0 AT1by the SARS-CoV-2 receptor ACE2. Interestingly, compared to WT SARS-CoV-2, ACE2 receptor phosphorylation at s680 produces conformational alterations in all types of SARS-CoV-2. Furthermore, our results showed for the first time that this phosphorylation significantly influences ACE2 sites K625, K676, and R678, which are key mediators for ACE2-B 0 AT1 complex., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: Several methods for synthesizing 2-thiohydantoin derivatives have been devised and exploited, and they have found widespread application as antioxidants, antimicrobials, antivirals, and anticancer agents. As a result, we tried to understand the underlying processes of the 2- thiohydantoin derivative's anti-LIHC activity., Methods: We predicted the anticancer mechanism of N-(4-oxo-5-(2-oxo-2-(p-tolylamino)ethyl)-3- phenyl-2-thioxoimidazolidin-1-yl)benzamide as a derivative of 2-thiohydantoin by utilizing molecular docking and molecular dynamic simulation. Furthermore, based on the results of molecular dynamic modelling, we employed bioinformatics to anticipate the immunotherapy of this molecule in the tumor microenvironment (TME) of Liver Hepatocellular Carcinoma (LIHC) patients. Next, we examined how this derivative affected proliferation, cell cycle progression, reactive oxygen species production, and apoptosis in HepG2 cancer cells., Results: Substantially, our investigation revealed that the IC50 value was 2.448 μM and that it arrested the cell cycle of HepG2 in the S phase. Furthermore, molecular docking and dynamics studies revealed a worthy interaction of this compound with AKT1 and CDK2 proteins. Considerably, AKT1 and CDK2 have negative affinity energies of -10.4 kcal/mol and -9.6 kcal/mol, respectively. Several bioinformatic tools were used in this investigation to provide insight into the future clinical application of this derivative as a novel candidate to target immune cells such as macrophages, neutrophils, eosinophils, and CD8+ T cells., Conclusion: The relevance of this 2-thiohydantoin derivative was demonstrated by our experimental tests, docking studies, and bioinformatics analysis, and it may be investigated as a lead molecule for anticancer medicines, notably as AKT1 and CKD2 inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Studying the structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein is important to understand the infection process. The S protein is necessary in completing the virus life cycle and is responsible for the appearance of new variants and drug and vaccine resistance. Understanding the structure and dynamics of biological macromolecules is essential for understanding how they function. In this work, we investigated the effects of mutations on S protein stability and solubility through molecular dynamic (MD) simulation in a 100 ns (ns) period. We screened four variants in addition to the wild type (WT). Results show that changes on MD simulation parameters of S protein indicate fluctuations and changes in the conformation, especially in the area between 300 and 600 amino acids (aa). This provides us an image of how the virus protein can reshape itself to adapt to any changes that occur in human angiotensin-converting enzyme 2 or drugs that can target the protein region. Our results also show that the Brazil variant has high fluctuations and unstable folding at some stages compared with other variants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)