Otilonium bromide ameliorates pulmonary fibrosis in mice through activating phosphatase PPM1A.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy.

Hepatocyte CHRNA4 mediates the MASH-promotive effects of immune cell-produced acetylcholine and smoking exposure in mice and humans.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading risk factor for liver cirrhosis and hepatocellular carcinoma. Here, we report that CHRNA4, a subunit of nicotinic acetylcholine receptors (nAChRs), is an accelerator of MASH progression. CHRNA4 also mediates the MASH-promotive effects induced by smoking.

Vincamine as an agonist of G protein-coupled receptor 40 effectively ameliorates pulmonary fibrosis in mice.

Background: Pulmonary fibrosis (PF) is an irreversible and fatal lung disease with limited therapeutic options. G protein-coupled receptor 40 (GPR40) has been developed as a promising therapeutic target for metabolic disorders and functions potently in varied pathological and physiological processes. Vincamine (Vin) is a monoterpenoid indole alkaloid originated from Madagascar periwinkle and was reported as a GPR40 agonist in our previous work.

Farnesyl diphosphate synthase exacerbates nonalcoholic steatohepatitis via the activation of AHR-CD36 axis.

Nonalcoholic steatohepatitis (NASH) has become a major concern that threatens human health worldwide. The underlying pathogenesis was crucial but remained poorly understood. Here, we found that the expression of hepatic farnesyl diphosphate synthase (FDPS) was increased in mice and patients with NASH.

Magnolol effectively ameliorates diabetic peripheral neuropathy in mice.

Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking efficient treatment. Magnolol (MG), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, is a natural product derived from Magnolia officinalis and widely used to treat a variety of diseases as a traditional Chinese medicine and Japanese Kampo medicine.

Purpose: Here, we aimed to investigate the potential of MG in ameliorating DPN-like pathology in mice and decipher the mechanism of MG in treating DPN.

Ipriflavone as a non-steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication with hallmarks of loss of learning ability and disorders of memory and behavior. Glucocorticoid receptor (GR) dysfunction is a main reason for neuronal impairment in brain of diabetic patients. Here, we determined that ipriflavone (IP) a clinical anti-osteoporosis drug functioned as a non-steroidal GR antagonist and efficiently ameliorated learning and memory dysfunction in both type 1 and 2 diabetic mice.

Amlodipine, an anti-hypertensive drug, alleviates non-alcoholic fatty liver disease by modulating gut microbiota.

Background And Purpose: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s.

Aryl Hydrocarbon Receptor Deficiency in Intestinal Epithelial Cells Aggravates Alcohol-Related Liver Disease.

Background & Aims: The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR) can sense xenobiotics, dietary, microbial, and metabolic cues. Roles of Ahr in intestinal epithelial cells (IECs) have been much less elucidated compared with those in intestinal innate immune cells. Here, we explored whether the IEC intrinsic Ahr could modulate the development of alcohol-related liver disease (ALD) via the gut-liver axis.

Mebhydrolin ameliorates glucose homeostasis in type 2 diabetic mice by functioning as a selective FXR antagonist.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic disease with hallmarks of hyperglycemia and hyperlipidemia. Long-term hyperglycemia damages the functions of multiple tissues and organs leading to a series of complications and disability or even death. Nuclear receptor farnesoid X receptor (FXR) antagonism has been recently discovered to exhibit beneficial effect on glucose metabolism in T2DM mice, although the underlying mechanisms remain unclear.

Coordinated changes of gut microbiome and lipidome differentiates nonalcoholic steatohepatitis (NASH) from isolated steatosis.

Background & Aims: Nonalcoholic fatty liver disease encompasses isolated steatosis or nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). NASH develops from isolated steatosis with obscure driving forces. We aim to identify key factors promoting this transition.

WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice.

The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited.

Chitosan Oligosaccharide Ameliorates Nonalcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Mice.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota.

Pharmacokinetics of a new ivermectin/praziquantel suspension after intramuscular administration in sheep.

A new oil suspension containing 0.10% ivermectin (IVM) and 15% praziquantel (PZQ) (Tivm+pzq) for intramuscular injection was developed for sheep, and its pharmacokinetics was investigated in sheep. The quality of the new product met the technical standards set by the Ministry of Agriculture of the People's Republic of China.

Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus.

The combination of baicalein (the active constituent of Scutellaria baicalensis) with penicillin G/amoxicillin showed potent synergy against 20 clinical penicillinase-producing Staphylococcus aureus strains including 10 isolates that were additionally methicillin-resistant (MRSA). The fractional inhibitory concentration (FIC) indices of penicillins+baiclein ranged from 0.14 to 0.

Mequindox resistance and in vitro efficacy in animal-derived Escherichia coli strains.

This study investigated the in vitro efficacy of mequindox against enteropathogenic Escherichia coli (EPEC), and characterized the oqxAB genes as the main mequindox resistance determinant in E. coli strains of animal origin. A total of 1123 E.