Discovery of novel oxindole derivatives as TRPA1 antagonists with potent analgesic activity for pain treatment.

Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in detecting harmful stimuli and endogenous ligands, primarily expressed in sensory neurons. Due to its role in pain and itch, TRPA1 is a potential drug target. We identified an oxindole core structure via high-throughput screening, modified it, and tested the modified compounds in vitro and in vivo.

Identify the key genes and pathways of melatonin in age-dependent mice hippocampus regulation by transcriptome analysis.

Context: Dysregulation of energy metabolism is a fundamental contributor to all the hallmarks of brain aging. Melatonin, primarily secreted by the pineal gland, is closely associated with molecules and signaling pathways that sense and affect energy metabolism. However, the impact of melatonin on age-related mRNA expression in the hippocampus of mice at different ages remains poorly understood.

A Mycorrhiza-Induced UDP-Glucosyl Transferase Negatively Regulates the Arbuscular Mycorrhizal Symbiosis.

Most terrestrial plants can establish a reciprocal symbiosis with arbuscular mycorrhizal (AM) fungi to cope with adverse environmental stresses. The development of AM symbiosis is energetically costly and needs to be dynamically controlled by plants to maintain the association at mutual beneficial levels. Multiple components involved in the autoregulation of mycorrhiza (AOM) have been recently identified from several plant species; however, the mechanisms underlying the feedback regulation of AM symbiosis remain largely unknown.

Regulating role of Pleurotus ostreatus insoluble dietary fiber in high fat diet induced obesity in rats based on proteomics and metabolomics analyses.

This study aims to reveal the effects of Pleurotus ostreatus insoluble dietary fiber (POIDF) on liver protein and cecal metabolites in obese rats and its potential mechanism by intestinal microbes. It was found that POIDF contained the structural characteristics of cellulose and hemicellulose, as well as amorphous diffraction peaks. POIDF could reduce the body weight and organ index of obese rats, regulate dyslipidemia, and improve the pathological changes of liver and epididymis fat.

The potential role of transcription factor sterol regulatory element binding proteins (SREBPs) in Alzheimer's disease.

Sterol regulatory element binding proteins (SREBPs) are a series of cholesterol-related transcription factors. Their role in regulating brain cholesterol biosynthesis, amyloid accumulation, and tau tangles formation has been intensively studied in protein-protein interaction analysis based on genes in clinical databases. SREBPs play an important role in maintaining cholesterol homeostasis in the brain.

Effect and mechanism of novel HDAC inhibitor ZDLT-1 in colorectal cancer by regulating apoptosis and inflammation.

Background: Histone deacetylase (HDAC) is a potential target for Colorectal Cancer (CRC) molecular target therapy, dehydroharmine derivative ZDLT-1 was designed to inhibit CRC cell proliferation by inhibiting HDAC target. This study aimed to explore the effect of ZDLT-1 could induce apoptosis in CRC in vitro and in vivo, and determine the mechanism of ZDLT-1.

Methods: First, MTT assay, colony formation, wound healing, Transwell assay, Hoechst33342 staining and Annexin V-FITC/PI double staining assay were used to investigate the in vitro effect of ZDLT-1.

Soluble TGF-β decoy receptor TGFBR3 exacerbates Alzheimer's disease pathology by modifying microglial function.

Alzheimer's disease (AD) is a major cause of progressive dementia characterized by memory loss and progressive neurocognitive dysfunction. However, the molecular mechanisms are not fully understood. To elucidate the molecular mechanism contributing to AD, an integrated analytical workflow was deployed to identify pivotal regulatory target within the RNA-sequencing (RNA-seq) data of the temporal cortex from AD patients.

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3.

Soluble transforming growth factor beta receptor 3 (sTGFBR3) antagonist is a new focus in the research and development of Alzheimer's disease (AD) drugs. Our previous studies have identified sTGFBR3 as a promising new target for AD, with few targeted antagonists identified. In this study, we performed structural modeling of sTGFBR3 using AlphaFold2, followed by high-throughput virtual screening and surface plasmon resonance assays.

Efficacy and safety of glucagon-like peptide-1 receptor agonists in the treatment of polycystic ovary syndrome-A systematic review and meta-analysis.

Context: Polycystic ovary syndrome (PCOS) is an endocrine gynaecological disorder that affects many women of childbearing age.

Objective: To evaluate the efficacy and safety of glucose-like peptide-1 receptor agonists for obese women with PCOS.

Methods: We searched the PubMed, Embase, WOS, and Cochrane Libarary databases up to June 2023.

Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer's Disease.

Targeting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been verified to regulate the progression of tau pathology as a promising treatment for Alzheimer's disease (AD), while the research progress on DYRK1A inhibitors seemed to be in a bottleneck period. In this work, we identified () as the most potential DYRK1A inhibitor (IC = 0.68 nM) through rational design, systematic structural optimization, and comprehensive evaluation.

Targeting cyclin-dependent kinases: From pocket specificity to drug selectivity.

The development of selective modulators of cyclin-dependent kinases (CDKs), a kinase family with numerous members and functional variations, is a significant preclinical challenge. Recent advancements in crystallography have revealed subtle differences in the highly conserved CDK pockets. Exploiting these differences has proven to be an effective strategy for achieving excellent drug selectivity.

Neutrophil extracellular traps formation may be involved in the association of propranolol with the development of portal vein thrombosis.

Background & Aims: Nonselective β blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs.

Materials And Methods: Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients.

The ADAM17 inhibitor ZLDI-8 sensitized hepatocellular carcinoma cells to sorafenib through Notch1-integrin β-talk.

ZLDI-8 is an A disintegrin and metalloproteinase domain 17 (ADAM17) inhibitor that suppresses the shedding of Notch1 to the Notch1 intracellular domain (NICD). In previous studies, we found that ZLDI-8 was able to sensitize HCC to sorafenib, but the mechanism of action remains unclear. The sensitizing effects of ZLDI-8 were tested both in vitro and in vivo.

A New Cell Model Overexpressing sTGFBR3 for Studying Alzheimer's Disease .

Background: Recent studies have suggested that abnormal microglial hyperactivation has an important role in the progression of Alzheimer's disease (AD). sTGFBR3 (a shed extracellular domain of the transforming growth factor type III receptor) is a newly identified target of microglia polarization dysregulation, whose overexpression can cause abnormal accumulation of transforming growth factor β1 (TGF-β1), promoting Aβ, tau, and neuroinflammatory pathology.

Objective: The objective of this study is to develop and validate a new cell model overexpressing sTGFBR3 for studying AD in vitro.

Association of non-selective β blockers with the development of renal dysfunction in liver cirrhosis: a systematic review and meta-analysis.

Background & Aims: Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association.

Methods: PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients.

Incidence of renal cell carcinoma after solid organ transplantation: a systematic review and meta-analysis.

Background: The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk.

Methods: PubMed, Embase and the Cochrane Library from their inception until August 16,2023.

Discovery of novel harmine derivatives as GSK-3β/DYRK1A dual inhibitors for Alzheimer's disease treatment.

Multitarget-directed ligands (MTDLs) have recently attracted significant interest due to their superior effectiveness in multifactorial Alzheimer's disease (AD). Combined inhibition of two important AD targets, glycogen synthase kinase-3β (GSK-3β) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), may be a breakthrough in the treatment of AD. Based on our previous work, we have designed and synthesized a series of novel harmine derivatives, investigated their inhibition of GSK-3β and DYRK1A, and evaluated a variety of biological activities.

Gonadotropin-Releasing Hormone Agonists during Gonadal Chemotherapy for the Effect on Pregnancy Outcome and Ovarian Function in Premenopausal Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

Objectives: The aim of this study was to evaluate the effects of gonadotropin-releasing hormone agonists (GnRHas) on pregnancy outcomes, premature ovarian failure (POF), menstrual recovery, disease-free survival (DFS), and adverse events in premenopausal breast cancer patients during gonadal chemotherapy.

Methods: We systematically searched PubMed, Cochrane Library, and Embase databases. The trials were eligible if they included premenopausal breast cancer patients treated with chemotherapy alone or with concurrent GnRHa and reported ovarian function recovery data.

Case Report: ALK rearranged locally advanced lung adenocarcinoma showing inconsistent radiographic findings and pathological responses during neoadjuvant alectinib therapy.

Alectinib has been approved as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinoma. Oncologists are also exploring the possibility of applying alectinib in the perioperative period. Here, we present a patient with locally advanced lung adenocarcinoma associated with - fusion mutation, who received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy.