Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.

Aims: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

Methods: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

Repercussion of SARS-CoV-2 on the Sexual Function in Males Updated Review.

SARS-CoV-2, also called coronavirus causes SARS-CoV-2 or severe acute respir-atory syndrome, a highly transmissible disease that has rapidly spread worldwide, straining healthcare systems and leading to a substantial number of fatalities. Interestingly, SARS-CoV-2 has revealed a gender difference, with males dying at a greater rate and with more severe cases than women. It's worth noting that the male reproductive system might be par-ticularly susceptible to damage during periods of moderate to severe sickness, which has been linked to cases of orchitis and erectile dysfunction.

Exploring the effects of probiotics on olanzapine-induced metabolic syndrome through the gut microbiota.

Background: Maintaining gut microbial homeostasis is crucial for human health, as imbalances in the gut microbiota (GM) can lead to various diseases, including metabolic syndrome (MS), exacerbated by the use of antipsychotic medications such as olanzapine (OLZ). Understanding the role of the GM in OLZ-induced MS could lead to new therapeutic strategies. This study used metagenomic analysis to explore the impact of OLZ on the GM composition and examined how probiotics can mitigate its adverse effects in a rat model.

Decoding multiple sclerosis: Unravelling the complexities of pathogenesis, progression, mechanisms and therapeutic innovations.

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.

Intrinsic Chirality Modulation and Biosensing Application of Helical Gold Nanorods by Anisotropic Etching.

The investigation of plasmonic chirality is a profound and intriguing topic, and the distinctive morphology of intrinsically chiral nanoparticles has prompted significant interest in the structure-activity relationship between particle morphology and chirality. In this work, the anisotropic etching of chiral helical gold nanorods (HGNRs) by a cetyltrimethylammonium bromide (CTAB)-HAuCl complex was observed with an interesting bidirectional variation of intrinsic chirality that initially enhanced and subsequently weakened, which was related with the diversity in CTAB distribution. In addition, an ultrasensitive and convenient sensing platform for acetylcholinesterase was developed based on the circular dichroism signal recovery of HGNRs caused by the dual inhibition of HGNR etching.

Development of Timolol Maleate-Loaded Poloxamer-co-Poly (acrylic acid) based hydrogel for controlled drug delivery.

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out.

Multi-Modal CLIP-Informed Protein Editing.

Proteins govern most biological functions essential for life, and achieving controllable protein editing has made great advances in probing natural systems, creating therapeutic conjugates, and generating novel protein constructs. Recently, machine learning-assisted protein editing (MLPE) has shown promise in accelerating optimization cycles and reducing experimental workloads. However, current methods struggle with the vast combinatorial space of potential protein edits and cannot explicitly conduct protein editing using biotext instructions, limiting their interactivity with human feedback.

Photoinduced Radical Relay Reaction of 2-Methylthiolated Phenylacetylenes/Alkynones Initiated by Electron Donor-Acceptor Complexes.

A method was found to construct sulfur-containing five- and six-membered heterocyclic alkyl sulfonyl compounds by using visible light and free radicals activated and/or generated by EDA complexes/homolytic cleavage as initiators to stimulate the relay reaction of alkynes/alkynones. This method puts forward a new strategy to initiate alkyl sulfonation of alkynes/alkynones with only a catalytic amount of the initiator. This strategy of generating the initiator by EDA complex activation/homolytic cleavage provides a new idea for the following substances that must be excited.

[Research progress on chemical constituents, pharmacological effects and molecular pharmacognosy of Zhejiang Ophiopogonis Radix].

Ophiopogonis Radix, a well-known Chinese herb, is dominantly cultivated in Zhejiang and Sichuan provinces, with the Zhejiang Ophiopogonis Radix acting as one of the eight Zhejiang-based traditional medical materials. Phytochemical studies have shown that Ophiopogonis Radix is rich in steroidal saponins, homoisoflavonoids, terpenoids, and polysaccharides, which collectively confer it with cardiovascular protection, anti-inflammation, anticancer, antioxidation, and immune regulation activities. Studies also show that Ophiopogonis Radix originated from Zhejiang and Sichuan is discriminated in both chemical components and clinical efficacy, while the existing reviews of Ophiopogonis Radix appear to pose a particular focus on Sichuan species, but not for Zhejiang origin.

[Chemical constituents and anti-inflammatory activity of Dracocephalum tanguticum].

The chemical constituents of Dracocephalum tanguticum were investigated using normal-and reverse-phase silica gel column chromatography, RP-HPLC, and other separation techniques, combined with experimental methods such as NMR, UV, IR, MS, and ORD, as well as comparison with reported literature data. From the ethanol extract of D. tanguticum, 10 compounds were isolated and identified: dracotangusion C(1),(1R,4S,5S,10R)-(+)-germacrone-1(10)-4-diepoxide(2), 1β,4β,5β-trihydroxy-7(11),9-germacradien-8-one(3), curcumadione(4), β-sitosterol(5), lilacoside(6), diosmetin-7-O-β-D-glucopyranoside(7), diosmin(8), luteolin-7-O-glucoside(9), and luteolin(10).

Discovery of marine ent-eudesmane sesquiterpenoids as angiogenic inhibitors via suppressing VEGF-A/VEGFR2 signaling pathway.

Increasing evidence underscores the pivotal role of tumor angiogenesis for tumorigenesis and tumor metastasis. Inhibiting the tumor angiogenesis process is a promising therapeutic approach for cancer. In order to search for natural angiogenic inhibitors, the chemical constitutes of a marine-derived fungus Eutypella sp.

Design, Synthesis, and Biological Evaluation of 2-Arylaminopyrimidine Derivatives as Dual Cathepsin L and JAK Inhibitors for the Treatment of Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by pulmonary inflammation, blood barrier functional disorder, and hypoxemia. Herein, a series of 2-aminopyrimidine derivatives were synthesized. Most of them exhibited inhibitory effects on inflammatory cytokines IL-6 and IL-8 in human bronchial epithelial (HBE) cells at a concentration of 5 μM without significant cytotoxicity.

Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for the treatment of rheumarthritis.

: Sitosterol, which is derived from (VR), is used for the treatment of rheumatoid arthritis (RA), but the pharmacological mechanisms through which sitosterol affects RA have not been fully elucidated. : Through the Traditional Chinese Medicine Systems Pharmacology and Analysis (TCMSP), PubChem, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases, "sitosterol-RA"-related genes were obtained, and a target protein interaction network (protein-protein interaction [PPI]) was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the intersecting genes.

Identification of phytomolecules as isoform and mutation specific PI3K-α inhibitor for protection against breast cancer using e-pharmacophore modeling and molecular dynamics simulations.

PI3K-α mutation plays a critical role in cancer development, notably in breast cancer, particularly within HR + /HER2- subtypes. These mutations drive tumor growth and survival by activating the PI3K/AKT/mTOR pathway, which is essential for cell proliferation and survival. Our research aimed to identify natural compounds that can inhibit mutant and specific isoforms of PI3K-α to prevent tumor progression.

Beyond peptides: Unveiling the design strategies, structure activity correlations and protein-ligand interactions of small molecule inhibitors against PD-1/PD-L1.

The landscape of cancer treatment has been transformed by the emergence of immunotherapy, especially through the use of antibodies that target the PD-1/PD-L1 pathway. Recently, there has been a notable increase in interest surrounding immune checkpoint inhibitors for cancer therapy. While antibody-based approaches have drawbacks like high costs and prolonged activity, the approval of monoclonal antibodies such as pembrolizumab and nivolumab has paved the way for a range of alternative therapies, including peptides, peptidomimetics, and small-molecule inhibitors.

EvaluationMaster: A GUI Tool for Structure-Based Virtual Screening Evaluation Analysis and Decision-Making Support.

Structure-based virtual screening (SBVS) plays an indispensable role in the early phases of drug discovery, utilizing computational docking techniques to predict interactions between molecules and biological targets. During the SBVS process, selecting appropriate target structures and screening algorithms is crucial, as these choices significantly shape the outcomes. Typically, such selections require researchers to be proficient with multiple algorithms and familiar with evaluation and analysis processes, complicating their tasks.

Advances in the Delivery, Activation and Therapeutics Applications of Bioorthogonal Prodrugs.

Traditional prodrug strategies have been leveraged to overcome many inherent drawbacks of active native drugs in the drug research and development. However, endogenous stimuli such as specific microenvironment or enzymes are relied on to achieve the prodrug activation, resulting in unintended drug release and systemic toxicity. Alternatively, bioorthogonal cleavage reaction-enabled bioorthogonal prodrugs activation via exogenous triggers has emerged as a valuable approach, featuring spatiotemporally controlled drug release.

Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and Cytotoxicity.

New derivatives -, , -, -, , , , -, -, and were synthesized and evaluated for their VEGFR-2 inhibition. Compounds , , and showed remarkable enzyme inhibition IC = 57.1, 42.

Evaluations of digital public health interventions in the WHO Southeast Asia Region: a systematic literature review.

Introduction: Digital health technologies have been enhancing the capacity of healthcare providers and, thereby, the delivery of targeted health services. The Southeast Asia Region (SEAR) has invested in strengthening digital public health. Many digital health interventions have been implemented in public health settings but are rarely assessed using the holistic health technology assessment (HTA) approach.

New complete genome insights into Enterobacter roggenkampii FACU2: a potential player in cadmium bio-removal.

Industrial workplaces, particularly those involved in ore processing or smelting, pose a high risk of exposure to cadmium, a highly toxic metal. This study isolated and identified eight cadmium-resistant strains from industrial wastewater for their ability to resist cadmium. Enterobacter roggenkampii FACU2 demonstrated exceptional cadmium removal capabilities during our analysis, successfully eliminating 62% of the cadmium.

Neuregulin 1 improved gastric motility and reduced gastric inflammation by activating the α7nAChR through the cholinergic anti-inflammatory pathway in diabetic rats.

Diabetic gastroparesis (DGP), a prevalent complication of diabetes, is characterized by delayed gastric emptying and inflammation. The dorsal motor nucleus of the vagus (DMV) plays a crucial role in modulating gastric function via the vagus nerve. Neuregulin 1 (NRG1), which is present in the DMV and influences the autonomic nervous system, has an unclear role in DGP.

Trailblazing real-world-data to confront hepatocellular carcinoma - disinterring repurposable drugs by amalgamating avant-garde stratagems.

Drug repurposing is preferred over de-novo drug discovery to unveil the therapeutic applications of existing drug candidates before investing considerable resources in unexplored novel chemical entities. This study demonstrated multifaceted stratagems to reconnoiter promising repurposable candidates against Hepatocellular Carcinoma (HCC) by amalgamating Real-World-Data (RWD) with bioinformatics algorithms corroborated with and studies. At the outset, the RWD from the Food and Drug Administration Adverse Event Reporting System (FAERS) was explored to navigate signals to retrieve repurposable drugs that are inversely associated with HCC via Disproportionality Analysis.

Anti-Inflammatory and Neurotrophic Factor Production Effects of 3,5,6,7,8,3',4'-Heptamethoxyflavone in the Hippocampus of Lipopolysaccharide-Induced Inflammation Model Mice.

Citrus fruits contain several bioactive components. Among them, one of the major components is 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), which has previously shown protective effects in the brain in some disease models; moreover, HMF has been shown to penetrate the brain. In recent years, inflammation has been identified as a defense response in the body; however, a chronic inflammatory response may trigger several diseases.

Assessment of Piperacillin-Tazobactam Population Pharmacokinetic Models in Neonates: An External Validation.

Background And Objective: Neonatal pharmacotherapy has gained attention from clinicians and regulatory agencies for optimizing the dosage of the drug which improves therapeutic outcomes in this special population. Piperacillin-tazobactam antibiotic is commonly used as a therapeutic option for treatment of severe infection in neonatal intensive care units. There are few population pharmacokinetic (PopPK) studies of piperacillin and tazobactam published for this specific population and which were not validated in other study settings.