SMA mice

BACKGROUND: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant anti-inflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases...

Objective: To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs). Methods: The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3rd to 5th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer ( n =3) at 24 h after culture...

PURPOSE: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms. METHODS: Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control...

In the study, we have shown the efficacy of an indigenously developed redox balancing chitosan gel with impregnated citrate capped Mn3 O4 nanoparticles (nanogel). Application of the nanogel on a wound of preclinical mice model shows role of various signaling molecules and growth factors, and involvement of reactive oxygen species (ROS) at every stage, namely hemostasis, inflammation, and proliferation leading to complete maturation for the scarless wound healing. While in vitro characterization of nanogel using SEM, EDAX, and optical spectroscopy reveals pH regulated redox buffering capacity, in vivo preclinical studies on Swiss albino involving IL-12, IFN-γ, and α-SMA signaling molecules and detailed histopathological investigation and angiogenesis on every stage elucidate role of redox buffering for the complete wound healing process...

Persistent activation of hepatic stellate cells (HSCs) in the injured liver leads to the progression of liver injury from fibrosis to detrimental cirrhosis. In a previous study, we have shown that survivin protein is upregulated during the early activation of HSCs, which triggers the onset of liver fibrosis. However, the therapeutic potential of targeting survivin in a fully established fibrotic liver needs to be investigated. In this study, we chemically induced hepatic fibrosis in mice using carbon tetrachloride (CCl4) for 6 weeks, which was followed by treatment with a survivin suppressant (YM155)...

This study was performed to investigate the protective effects of Allium ochotense on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of a mixture of aqueous and 60% ethanol (2:8, w / w ) extracts of A. ochotense (EA) were identified as kestose, raffinose, kaempferol and quercetin glucoside, and kaempferol di-glucoside by UPLC Q-TOF MSE . The EA regulated the levels of lipid metabolism-related biomarkers such as total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)-cholesterol in serum...

Targeting epigenetic mechanisms has emerged as a potential therapeutic approach for the treatment of kidney diseases. Specifically, inhibiting the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1 has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, its clinical translation faces challenges due to issues with poor pharmacokinetics and side effects. Here, we developed engineered liposomes loaded with JQ1 with the aim of enhancing kidney drug delivery and reducing the required minimum effective dose by leveraging cargo protection...

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes. The obese diabetic Leprdb/db mice (db/db) were used for behavioral assessments and subsequent morphological examinations...

BACKGROUND: Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial-mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD...

BACKGROUND: Circular RNAs ( CircRNAs ) have been shown to be involved in the development of chronic kidney disease (CKD). This study aimed to investigate the role of Circ1647 in renal fibrosis, which is a hallmark of CKD. METHODS: In this study, we established a unilateral ureteral obstruction (UUO) model and delivered Circ1647 RfxCas13d knockdown plasmid into renal parenchymal cells via retrograde injection through the ureter followed by electroporation. After that, the pathological changes were determined by Hematoxylin and Eosin...

Hyaluronidases (HAases) are enzymes that degrade hyaluronic acid (HA) in the animal kingdom. The HAases-HA system is crucial for HA homeostasis and plays a significant role in biological processes and extracellular matrix (ECM)-related pathophysiological conditions. This study aims to explore the role of inhibiting the HAases-HA system in acute kidney injury (AKI). We selected the potent inhibitor "sHA2.75" to inhibit HAase activity through mixed inhibitory mechanisms. The ischemia-reperfusion mouse model was established using male BALB/c mice (7-9 weeks old), and animals were subjected to subcapsular injection with 50 mg/kg sHA2...

BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages...

BACKGROUND: Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated. METHODS: Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery...

BACKGROUND: The prevalence of obesity is increasing worldwide at an alarming rate. In addition to the increased incidence of cardiovascular and metabolic diseases, obesity is the most potent risk factor for developing chronic kidney disease (CKD). Although systemic events such as hemodynamic factors, metabolic effects, and lipotoxicity were implicated in the pathophysiology of obesity-related glomerulopathy (ORG) and kidney dysfunction, the precise mechanisms underlying the association between obesity and CKD remain unexplored...

Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduces pressure overload-induced cardiac fibrosis and improves cardiac dysfunction in male mice. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppress α-smooth muscle actin (α-SMA) expression induced by transforming growth factor-β (TGF-β) in cultured cardiac fibroblasts...

OBJECTIVE: To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms. METHODS: BALB/C mice (7 to 8 weeks old) were divided into normal group, CCl4 group, CCl4 +AAV-NC group and CCl4 +AAV-NDU13 group ( n =18). Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3, 5 or 7 weeks, and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection...

BACKGROUND AND OBJECTIVE: Forkhead box-O 1 (FOXO1) is a transcription factor actively involved in oral wound healing at the epithelial barrier. However, less is known regarding the role of FOXO1 during the tissue repair response in the connective tissue compartment. This study explored the involvement of FOXO1 in the modulation of fibroblast activity related to wound healing. METHODS: Primary cultures of human gingival fibroblasts were obtained from four healthy young donors...

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic form of non-alcoholic fatty liver disease. Liver fibrosis leads to liver cancer and cirrhosis, and drug therapy for NASH remains lacking. Ninjin'yoeito (NYT) has shown antifibrotic effects in a model of liver fibrosis without steatosis but has not been studied for NASH. Therefore, we evaluated the efficacy of NYT in mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a NASH model. Compared with the normal diet group, mice fed CDAHFD showed decreased body weight and increased white adipose tissue, liver weight, and triglyceride content in the liver...

Cirrhosis is a familiar end-stage of multiple chronic liver diseases. The gene-modified mesenchymal stem cells (MSCs) have become one of the most promising schemes for the treatment of cirrhosis. MSCs exhibit their therapeutic role mainly by secreting hepatocyte growth factor (HGF). The aim of this research was to probe the anti-fibrosis role of exosomes secreted by HGF modified-mouse adipose MSCs (ADMSCs) on activated hepatic stellate cells (HSCs) and to preliminarily explore the possible mechanism. Firstly, mouse ADMSCs were isolated and identified...

Spinal muscular atrophy (SMA) is an autosomal recessive disease that affects 1 out of every 6,000-10,000 individuals at birth, making it the leading genetic cause of infant mortality. In recent years, reports of sex differences in SMA patients have become noticeable. The SMNΔ7 mouse model is commonly used to investigate pathologies and treatments in SMA. However, studies on sex as a contributing biological variable are few and dated. Here, we rigorously investigated the effect of sex on a series of characteristics in SMA mice of the SMNΔ7 model...