Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

Background: For ages, botanical medicine has been used in the treatment of diabetes mellitus (DM). Notoginsenoside R1 (NGR1), a Panax notoginseng (Burkill) F.H.

mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.

The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging.

An Overview of the Role of Furin in Type 2 Diabetes.

Post-translational modifications (PTMs) play important roles in regulating several human diseases, like cancer, neurodegenerative disorders, and metabolic disorders. Investigating PTMs' contribution to protein functions is critical for modern biology and medicine. Proprotein convertases (PCs) are irreversible post-translational modifiers that have been extensively studied and are considered as key targets for novel therapeutics.

Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches.

Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I.

Exploring the Binding Mechanism of NRG1-ERBB3 Complex and Discovery of Potent Natural Products to Reduce Diabetes-Assisted Breast Cancer Progression.

Diabetes mellitus significantly contributes to breast cancer progression, where hyperglycemia upregulates specific genes, leading to more aggressive tumor growth. In patients with BC that develop diabetes, neuregulin 1 (NRG1) and epidermal growth factor receptor 3 (ERBB3) overexpression exacerbate tumor growth and progression. Since the interaction between NRG1 and ERBB3 is critical for tumor growth, understanding the molecular mechanisms underlying NRG1-ERBB3 complex formation is essential for elucidating diabetes-assisted breast cancer progression.

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase.

Ethnopharmacological Relevance: Ayurvedic medicine has been used in the treatment of diabetes mellitus for centuries. In Arabia and some areas of Africa, Commiphora myrrha (CM) has been extensively used as a plant-based remedy. We have previously shown that an aqueous CM resin solution directly stimulates insulin secretion from MIN6 cells, a mouse β-cell line, and isolated mouse and human islets.

Discovery of natural products to block SARS-CoV-2 S-protein interaction with Neuropilin-1 receptor: A molecular dynamics simulation approach.

Neuropilin-1 (NRP1) is a widely expressed cell surface receptor protein characterized by its pleiotropic function. Recent reports highlighted NRP1 as an additional entry point of the SARS-CoV-2 virus, enhancing viral infectivity by interacting with the S-protein of SARS-CoV-2. The ubiquitous distribution and mechanism of action of NRP1 enable the SARS-CoV-2 virus to attack multiple organs in the body simultaneously.

Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity.

Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78.

Molecular Simulation-Based Investigation of Highly Potent Natural Products to Abrogate Formation of the nsp10-nsp16 Complex of SARS-CoV-2.

The SARS-CoV-2 non-structural protein (nsp) nsp10-nsp16 complex is essential for the 2'-O-methylation of viral mRNA, a crucial step for evading the innate immune system, and it is an essential process in SARS-CoV-2 life cycle. Therefore, detecting molecules that can disrupt the nsp10-nsp16 interaction are prospective antiviral drugs. In this study, we screened the North African Natural Products database (NANPDB) for molecules that can interact with the nsp10 interface and disturb the nsp10-nsp16 complex formation.

Outcomes of COVID-19: Disparities by ethnicity.

Objectives: To investigate the role of ethnicity in COVID-19 outcome disparities in a cohort in Kuwait.

Methods: This is a retrospective analysis of 405 individuals infected with SARS-CoV-2 in Kuwait. Outcomes such as symptoms severity and mortality were considered.

Higher binding affinity of furin for SARS-CoV-2 spike (S) protein D614G mutant could be associated with higher SARS-CoV-2 infectivity.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614G substitution in the severe acute respiratory syndome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S protein), which may affect viral infectivity.

Methods: The effect of D614G substitution on the structure and thermodynamic stability of the S protein was analyzed with use of DynaMut and SCooP.

Comparative Proteomic Analysis Identifies EphA2 as a Specific Cell Surface Marker for Wharton's Jelly-Derived Mesenchymal Stem Cells.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, a proteomic approach was employed to identify specific proteins differentially expressed by WJ-MSCs in comparison to those by neonatal foreskin and adult skin fibroblasts (NFFs and ASFs, respectively).

Structural analysis of ACE2 variant N720D demonstrates a higher binding affinity to TMPRSS2.

Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel member of the betacoronaviruses family affecting the lower respiratory tract mainly through binding to angiotensin converting enzyme 2 (ACE2) via its S-protein. Genetic analysis of (ACE2) gene revealed several variants that have been suggested to regulate the interaction with S protein. This study investigates the N720D variant, positioned in the collectrin-like domain (CLD) at proximity to type II transmembrane serine protease (TMPRSS2) cleavage site.

Palmitic acid-induced lipotoxicity promotes a novel interplay between Akt-mTOR, IRS-1, and FFAR1 signaling in pancreatic β-cells.

Background: Free fatty acid receptor 1 (FFAR1) is G-protein coupled receptor predominantly expressed in pancreatic β-cells that is activated by a variety of free fatty acids (FFAs). Once activated, it promotes glucose-stimulated insulin secretion (GSIS). However, increased levels of FFAs lead to lipotoxicity, inducing loss of β-cell function.