DNA methylation: The epigenetic mechanism of Alzheimer's disease.

Nowadays, with the development of the social health care system, there is an increasing trend towards an aging society. The incidence of Alzheimer's disease (AD) is also on the rise. AD is a kind of neurodegenerative disease that can be found in any age group. For years, scientists have been committing to discovering the cause of AD. DNA methylation is one of the most common epigenetic mechanisms in mammals and plays a vital role in the pathogenesis of several diseases, including tumors. Studying chemical changes in the epigenome, or DNA methylation can help us understand the effects of our environment and life on diseases, such as smoking, depression, and menopause, which may affect people's chances of developing Alzheimer's or other diseases. Recent studies have identified some crucial genes like ANK1, RHBDF2, ABCA7, and BIN1, linking DNA methylation to AD. This review focuses on elucidating the relationship between DNA methylation and the pathogenesis of AD and provides an outlook on possible targeted therapeutic modalities.

Efficacy of the lumbar sympathetic ganglion block in lower limb pain and its application prospects during the perioperative period.

The sympathetic nervous system is involved in the physiological pathogenesis of many different types of chronic pain. Sympathetic blocks can interrupt the reflex control system by intercepting the noxious afferent fibers accompanying autonomic nerves, resulting in changes in peripheral or central sensory processing. A lumbar sympathetic ganglion block (LSGB), as a treatment method, refers to the injection of nerve blockers into the corresponding lumbar sympathetic nerve segments, usually requiring imaging assistance (CT, X-ray, ultrasound) to guide. At present, LSGB has been widely used in the clinical treatment of lower limb pain, such as neuropathic pain, lower limb ischemic pain, and so on. Its mechanism of action may be through inhibiting sympathetic nerve activity and dilating blood vessels, thereby alleviating pain and inhibiting stress response. However, there are few reports of LSGB during the perioperative period, especially in postoperative pain and gastrointestinal function. Therefore, by studying the literature about LSGB-related studies, this article reviews the anatomy of the lumbar sympathetic nerve (LSN), with its clinical application and possible mechanism. We reviewed the analgesic effect of LSGB in patients with lower limb pain and postoperative pain and the potential application prospects in the recovery of gastrointestinal function, finally providing a reference for its clinical application.

MiR-127-3p targeting CISD1 regulates autophagy in hypoxic-ischemic cortex.

Neonatal hypoxic-ischemic (HI) injury derived from asphyxia during perinatal period, is a serious complication of neonatal asphyxia and the main cause of neonatal acute death and chronic neurological injury. Aberrant autophagy occurs in many nervous system diseases, but its role and underlying mechanism in HI injury is largely unknown. Here, we successfully constructed a newborn rat model of HI brain injury, and the knockout-miR-127-3p (KO-miR-127-3p) rats were structured by using CRISPR/Cas9. Subsequently, the in vitro functional experiments, in vivo zea-longa scores, as well as bioinformatics analyses and biological experiments were applied. The expression of autophagy-related proteins, including ATG12, P62, Beclin-1, LC3II in HI cortex with miR-127-3p knockout was significantly decreased, and autophagic vacuoles were disappeared. Moreover, miR-127-3p has a specific regulatory effect on CISD1 expression, another crucial molecule in autophagy process. Accordingly, the overexpression of CISD1 effectively inhibited the autophagic cell death and physiological dysfunction in the brain of HI injury, whereas si-CISD1 reversed the neuroprotective effects of KO-miR-127-3p. Our findings explained the underlying mechanism for HI injury, and miR-127-3p targeting CISD1 signal could be supposed as a new treatment strategy to prevent and treat HI injury.

Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice.

AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. METHODS: Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. RESULTS: The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. CONCLUSION: EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.

Effects of Jitai tablet, a traditional Chinese medicine, on plasma adrenocorticotropic hormone and cortisol levels in heroin addicts during abstinence.

OBJECTIVES: To investigate the changes in adrenocorticotropic hormone (ACTH) and cortisol in heroin addicts given Jitai tablet treatment during abstinence. DESIGN: Double-blind, randomized, placebo-controlled clinical trial. SETTINGS/LOCATION: Drug Rehabilitation Bureau of Shanghai Police, China. PARTICIPANTS: 99 volunteers, including 69 heroin addicts and 30 healthy volunteers. INTERVENTIONS: 69 heroin addicts randomly divided into two groups: the Jitai tablet group, which comprised 34 heroin addicts given Jitai tablet treatment during abstinence, and the placebo group, which comprised 35 heroin addicts given placebo. A control group consisted of 30 sex- and age-matched healthy volunteers. OUTCOME MEASURES: ACTH and cortisol in plasma were measured in all groups at baseline and in the Jitai tablet and placebo groups on the third, seventh, and 14th days of abstinence. RESULTS: Levels of both ACTH (p<.01) and cortisol (p<.001) were significantly higher in heroin addicts at baseline than in the healthy volunteers. Jitai tablet treatment restored plasma cortisol levels to normal more rapidly than did placebo treatment (p<.05), but not ACTH levels. A positive correlation between ACTH and cortisol values at baseline (p<.01) was also found with withdrawal symptom scores and daily dosages of heroin. CONCLUSIONS: Heroin addicts could respond to Jitai tablets through changes in the hypothalamus-pituitary-adrenal axis.

Triterpenoids from Ganoderma lucidum and their cytotoxic activities.

From the ethyl acetate fraction of the fruiting body of Ganoderma lucidum, a new triterpenoid, ethyl 7ß-hydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oate (4), named ethyl lucidenates A, along with three known compounds, ganodermanondiol (1), lucidumol B (2) and methyl lucidenates A (3) were isolated by silica gel column, ODS column chromatography and PHPLC. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The isolated compounds were tested using in vitro MTT assay for their cytotoxic activities against the K562, HL-60, CA46, HepG2, SW480 and SMMC-7221 cancer cell lines. Among them, compound 4 showed cytotoxicity against HL-60 and CA46 cancer cell lines with IC(50) values of 25.98 and 20.42 µg mL(-1), respectively.

Different effects of valproate on methamphetamine- and cocaine-induced behavioral sensitization in mice.

Repetitive exposure to psychostimulants elicits behavioral sensitization. Accumulating evidence have shown that the central GABAergic system is involved in psychostimulants sensitization. Valproate, a clinically widely used anticonvulsant mood-stabilizing agent, can modulate central GABAergic neurotransmission. Herein, the effects of valproate on the development and expression of behavioral sensitization to methamphetamine (METH) and cocaine was studied in mice. Behavioral sensitization of METH and cocaine was rendered by injection of METH (2.0mg/kg) or cocaine (20mg/kg) once daily for seven days. Locomotor activity was measured by an ambulometer. Single or multiple administration of valproate (37.5, 75, 150 mg/kg) could not decrease acute METH- and cocaine-induced hyperactivity. Co-administration of valproate with METH or cocaine dose-dependently inhibited the development of behavioral sensitization. Single administration of valproate (37.5, 75, 150 mg/kg) did not affect the expression of behavioral sensitization induced by METH and cocaine. Multiple administration of valproate (37.5, 75, 150 mg/kg) dose-dependently inhibited the expression of behavioral sensitization to METH, but not to cocaine. The present results supported that METH- and cocaine-induced behavioral sensitization possesses distinct neural mechanisms, which implies that valproate may have different modulatory effect on METH and cocaine addiction in humans.