Electroacupuncture improves cognitive dysfunction in rats with Alzheimer's disease by regulating microglial cells.

Objectives: To observe the effect of electroacupuncture (EA) on microglia (MG), Janus kinase-2 (JAK2) and signal transducer and activator of transcription-3 (STAT3) in hippocampal CA1 region of Alzheimer's di-sease (AD) rats, so as to explore its mechanisms in the treatment of AD.

Methods: Thirty-six male SD rats were randomly divided into sham operation, model and EA groups, with 12 rats in each group. The AD rat model was established by intraperitoneal injection of D-galactose combined with intrahippocampal injection of aggregated Aβ.

MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.

Background: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development.

[Effect of moxibustion on inositol requiring enzyme 1 / X-box binding protein 1 pathway in hippocampal CA1 region of rats with vascular dementia].

Objective: To observe the effect of moxibustion at Governor Vessel acupoints on inositol requiring enzyme 1 （IRE1） / X-box binding protein 1 （XBP1） pathway in hippocampal CA1 region of rats with vascular dementia （VD）, so as to explore its mechanisms in the treatment of VD.

Methods: Male SD rats were randomly divided into normal, sham operation, model, moxibustion （Moxi） and medication groups （n=12）. The VD model was established by permanent ligation of bilateral common carotid arteries.

[Mechanisms of moxibustion preconditioning underlying improving learning-memory ability by regulating polarization of microglia via TLR4/NF-κB signaling pathway in AD rats].

Objective: To observe the effect of moxibustion preconditioning on learning-memory ability, Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signal pathway related proteins and microglia in rats with Alzheimer's disease (AD), so as to explore its possible mechanisms underlying improvement of AD.

Methods: Male SD rats were randomly divided into normal, sham operation, AD model and pre-moxibustion groups, with 9 rats in each group. Moxibustion was applied to "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) for 15 min, once daily, 6 days as a course of treatment for 3 courses.

[Involvement of miR-126-3p via mTOR/HIF-1α signaling pathway in effect of electroacupuncture on angiogenesis in rats with cerebral ischemia].

Objective: To observe the effect of electroacupuncture (EA) on miRNA-126-3p and mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in rats with cerebral ischemia (CI), so as to explore the underlying mechanism of EA on angiogenesis.

Methods: Male SD rats were randomly divided into control group, model group, EA group and EA+inhibitor group (inhibitor group), which were further divided into 3, 7 and 14 d subgroups, with 12 rats in each sub-group. The CI model was established by occlusion of the middle cerebral artery.

Transjugular Transcatheter Tricuspid Valve Implantation of LuX-Valve Bioprosthesis in a Preclinical Model.

The purpose of this preclinical study in a sheep model was to confirm the feasibility and safety of the LuX-Valve transjugular tricuspid valve (TV) replacement apparatus and to optimize the implantation procedure before beginning first-in-man study. The LuX-Valve was implanted in a sheep model (n = 8) via transjugular approach. Six of eight sheep underwent successful implantation procedure on beating heart.

[Melatonin Induced Apoptosis of RPMI 8226 Cells through Endoplasmic Reticulum Stress].

Objective: To investigate the effect of melatonin (MLT) on the proliferation and apoptosis of human multiple myeloma cell line RPMI 8226 and its possible mechanism.

Methods: RPMI 8226 cells were cultured in vitro, and different concentrations of MLT were treated on RPMI 8226 cells. The effects of MLT on RPMI 8226 cell proliferation were detected by CCK-8 assay and methylcellulose cloning assay, and the effects of MLT on cell apoptosis were detected by AnnexinV-FITC /PI, flow cytometry.

[Effects of pre-moxibustion on expression of phosphorylated Tau protein and related protein kinases in hippocampal CA3 region of AD rats].

Objective: To observe the effect of pre-moxibustion at "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) on expression of Tau protein and related protein kinases as glycogen synthase kinase-3β (GSK-3β), etc. in the hippocampal CA3 region of Alzheimer's disease (AD) rats, so as to explore its mechanism underlying prevention and treatment of AD cognitive impairment.

Methods: Male SD rats were randomly divided into 4 groups: normal control, sham operation， model and pre-moxibustion，with 9 rats in each group.

[Effect of electroacupuncture of different acupoint groups on cerebral cortical neurovascular unit and PI3K/Akt signaling in rats with ischemic stroke].

Objective: To observe the protective effect of electroacupuncture (EA) on neurovascular unit, neurological function in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of ischemic cerebral tissue.

Methods: Male SD rats, SPF grade, were randomly and equally divided into sham operation group, model group, EA group Ⅰ and EA group Ⅱ，27 rats in each group. The CI model was established by occlusion of the middle cerebral artery (MCAO).

[Electroacupuncture combined with rehabilitation training improves regional cerebral blood flow and reduces infarct volume by promoting expression of angiogenesis-related factors in acute cerebral ischemia rats].

Objective: To observe the effect of electroacupuncture (EA) combined with rehabilitation training on regional cerebral blood flow (rCBF) and angiogenesis in rats with acute cerebral ischemia (ACI), so as to explore its mechanisms underlying improvement of ACI.

Methods: A total of 135 male SD rats were divided into 5 groups: sham-operation (sham), model, EA, rehabilitation training and EA+rehabilitation training (combined treatment) groups (=27 rats in each group). The ACI model was established by occlusion of the middle cerebral artery with thread embolus.

Priapism in a Fabry disease mouse model is associated with upregulated penile nNOS and eNOS expression.

Fabry disease is a glycosphingolipidosis caused by deficient activity of α-galactosidase A; it is one of a few diseases that are associated with priapism, an abnormal prolonged erection of the penis. The goal of this study was to investigate the pathogenesis of Fabry disease-associated priapism in a mouse model of the disease. We found that Fabry mice develop late-onset priapism.

Tetrahydrobiopterin deficiency in the pathogenesis of Fabry disease.

Fabry disease is caused by deficient activity of α-galactosidase A and subsequent accumulation of glycosphingolipids (mainly globotriaosylceramide, Gb3), leading to multisystem organ dysfunction. Oxidative stress and nitric oxide synthase (NOS) uncoupling are thought to contribute to Fabry cardiovascular diseases. We hypothesized that decreased tetrahydrobiopterin (BH4) plays a role in the pathogenesis of Fabry disease.

ANGPTL8 reverses established adriamycin cardiomyopathy by stimulating adult cardiac progenitor cells.

Established adriamycin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50% in a year. It has been known that ANGPTLs has various functions in lipid metabolism, inflammation, cancer cell invasion, hematopoietic stem activity and diabetes.

Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from Fabry mice.

Fabry disease is caused by deficient activity of α-galactosidase A and subsequent intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Vascular endothelial cells may play important roles in disease pathogenesis, and are one of the main target cell types in therapeutic interventions. In this study, we generated immortalized aortic endothelial cell lines from a mouse model of Fabry disease.

Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice.

Enzyme replacement therapy (ERT) is an effective treatment for several lysosomal storage disorders (LSDs). Intravenously infused enzymes are taken up by tissues through either the mannose 6-phosphate receptor (M6PR) or the mannose receptor (MR). It is generally believed that M6PR-mediated endocytosis is a key mechanism for ERT in treating LSDs that affect the non-macrophage cells of visceral organs.

In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats.

Aims/hypothesis: ANGPTL8 is a circulatory hormone secreted from liver and adipose tissue that promotes pancreatic beta cell proliferation and interferes with triacylglycerol metabolism in mice. The clinical significance of its effects on inducing beta cell proliferation is limited because it causes severe hypertriacylglycerolaemia.

Methods: We employed ultrasound-targeted microbubble destruction (UTMD) to deliver human ANGPTL8 gene plasmids to the pancreas, liver and skeletal muscle of normal adult rats.

Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice.

Fabry disease is caused by deficient activity of lysosomal enzyme α-galactosidase A. The enzyme deficiency results in intracellular accumulation of glycosphingolipids, leading to a variety of clinical manifestations including hypertrophic cardiomyopathy and renal insufficiency. The mechanism through which glycosphingolipid accumulation causes these manifestations remains unclear.

Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction.

Unlabelled: Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control.

Methods And Results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation.

HIV Tat Domain Improves Cross-correction of Human Galactocerebrosidase in a Gene- and Flanking Sequence-dependent Manner.

Krabbe disease is a devastating neurodegenerative lysosomal storage disorder caused by a deficiency of β-galactocerebrosidase (GALC). Gene therapy is a promising therapeutic approach for Krabbe disease. As the human brain is large and it is difficult to achieve global gene transduction, the efficacy of cross-correction is a critical determinant of the outcome of gene therapy for this disease.

Sex differences of urinary and kidney globotriaosylceramide and lyso-globotriaosylceramide in Fabry mice.

The aim of our study was to measure globotriaosylceramide (Gb(3)) and lyso-Gb(3) levels by tandem mass spectrometry in the urine and kidney in Fabry (gla knockout) mice and wild-type controls. We found that urine Gb(3) of male and female Fabry mice was higher than wild-type mice of the same sex but also significantly higher in male mice compared with females of the same genotype. In kidney tissue, sex and genotype-dependent differences in Gb(3) levels paralleled those in the urine.

Generation of induced pluripotent stem (iPS) cells derived from a murine model of Pompe disease and differentiation of Pompe-iPS cells into skeletal muscle cells.

Our study is the first to demonstrate the ability to generate iPS cells from a mouse model of Pompe disease. Initially, mouse tail tip fibroblasts were harvested from male, 8-week-old (GAA) knockout mice, and three reprogramming factors (Oct3/4, Sox2 and Klf4) were transfected into the isolated donor cells using a retroviral vector. These iPS cells also showed decreased levels of GAA enzymatic activity and strong positive staining with periodic acid-Schiff (indicating the accumulation of glycogen) and acid phosphatase (lysosomal activation marker).

Induced pluripotent stem cells derived from mouse models of lysosomal storage disorders.

Most lysosomal storage diseases (LSDs) are life-threatening genetic diseases. The pathogenesis of these diseases is poorly understood. Induced pluripotent stem (iPS) cell technology offers new opportunities for both mechanistic studies and development of stem cell- based therapies.

Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells.

Fabry disease, an X-linked systemic vasculopathy, is caused by a deficiency of alpha-galactosidase A resulting in globotriaosylceramide (Gb(3)) storage in cells. The pathogenic role of Gb(3) in the disease is not known. Based on previous work, we tested the hypothesis that accumulation of Gb(3) in the vascular endothelium of Fabry disease is associated with increased production of reactive oxygen species (ROS) and increased expression of cell adhesion molecules.

Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed lutropin/choriogonadotropin receptor.

Human chorionic gonadotropin (hCG) and LH play an important role in reproductive physiology. Both hCG and LH bind to the same LH/choriogonadotropin receptor (LH/CG-R). Recent reports documented the temporal and spatial expression of LH/CG-R in the developing and mature mammalian brain.