ASC Regulates Subcutaneous Adipose Tissue Lipogenesis and Lipolysis via p53/AMPKα Axis.

Obesity has become an extensive threat to human health due to associated chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) is a critical link between inflammasome and apoptosis-inducing proteins. In this study, we aimed to clarify the role of ASC in lipid metabolism.

Emerging single atom catalysts in gas sensors.

Single atom catalysts (SACs) offer unprecedented opportunities for high-efficiency reactions taking place in many important fields of catalytic processes, electrochemistry, and photoreactions. Due to their maximized atomic utilization and unique electronic and chemical properties, SACs can provide high activity and excellent selectivity for gas adsorption and electron transport, leveraging SACs that enhance the detection sensitivity and selectivity to target gases. In the past few years, SACs including both noble (Pt, Pd, Au, ) and non-noble (Mn, Ni, Zn ) metals have been demonstrated to be very useful in optimizing sensing performances.

Regulation of indoleamine 2, 3-dioxygenase in hippocampal microglia by NLRP3 inflammasome in lipopolysaccharide-induced depressive-like behaviors.

In the brain, NLRP3 (Nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin-domain-containing 3) inflammasome is mainly expressed in microglia located in the hippocampus and other mood-regulated regions, which are particularly susceptible to stress. The activation of NLRP3 inflammasome and production of the activation products may contribute to the development of depressive disorder and memory deficits. Indoleamine 2, 3-dioxygenase (IDO) is a key factor mediating inflammation and major depressive disorder (MDD).

Dexmedetomidine Protects Against Multi-Organ Dysfunction Induced by Heatstroke via Sustaining The Intestinal Integrity.

Previous studies have indicated that gut-derived endotoxin played a pivotal role for aggravating systemic inflammatory response to multi-organ dysfunction under heatstroke. Dexmedetomidine (DEX) could protect against inflammation and multi-organ injury in various scenarios. The aim of this study was to explore the protective effect of DEX on heatstroke and the mechanism involved.

NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation.

Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions.

Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation.

Background/aims: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored.

Methods: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of 60Coγ radiation.

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages.

A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death.

NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model.

Background: Abundant researches indicate that neuroinflammation has important roles in the pathophysiology of depression. Our previous study found that the NLRP3 inflammasome mediated stress-induced depression-like behavior in mice via regulating neuroinflammation. However, it still remains unclear that how the NLRP3 inflammasome influences related inflammatory signaling pathway to contribute to neuroinflammation in depression.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats.

Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use.

A comprehensive strategy using chromatographic profiles combined with chemometric methods: Application to quality control of Polygonum cuspidatum Sieb. et Zucc.

For the strict quality control of herbs, a comprehensive strategy based on chromatographic profiles and chemometric methods which could reliably select quantitative indices, robustly quantitate multi-markers and systematically compare different chemometric methods was proposed and successfully applied to the quality analysis of P. cuspidatum. Based on the construction of chromatographic profiles by an efficient accelerated solvent extraction (ASE) and reliable high-performance liquid chromatography-ultraviolet (HPLC-UV) methods, different chemometric methods were employed, namely similarity analyses (SA), hierarchical clustering analysis (HCA) and linear discriminant analysis (LDA).

Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats.

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B.

Toxicity of Smokeless Tobacco Extract after 184-Day Repeated Oral Administration in Rats.

The use of smokeless tobacco (ST) is growing rapidly and globally. The consumption of ST is associated with an increased risk for developing chronic diseases, such as diabetes, hypercholesterolemia, and myocardial infarction, and has led to many public health problems. It is very important to access the toxicity of ST.

Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery.

Background: Trabeculectomy is performed as a treatment for glaucoma to lower intraocular pressure (IOP). The surgical procedure involves creating a channel through the wall of the eye. However scarring during wound healing can block this channel which will lead to the operation failing.

Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn's disease? A meta-analysis.

Many studies have reported the association between the CARD8 gene polymorphism rs2043211 and the susceptibility to Crohn's disease (CD), but the results have remained quite contradictory. Therefore, the aim of the meta-analysis was to explore whether the CARD8 rs2043211 polymorphism has an effect on CD risk. We performed a systematic literature search for related articles published up to July 2014 in multiple databases.

Acute and subchronic toxicities of QX100626, a 5-HT4 receptor agonist, in rodents and Beagle dogs.

Serotonin 5-hydroxytryptamine 4(5-HT4) receptor agonists have been widely prescribed as a prokinetics drug for patients with gastro-esophageal reflux disease and functional dyspepsia. QX100626, one of the 5-HT4 receptor agonists, has been studied as a promising agent for this clinical use. The objective of the present study was to identify possible target organs of toxicity and propose a non-toxic dose of QX100626 for clinical usage.

Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

Previous studies have reported an association between vitamin D receptor (VDR) gene polymorphisms and Parkinson's disease (PD), but the results were controversial. To explore whether VDR gene polymorphisms have an effect on PD risk, we performed this meta-analysis to evaluate the association between three VDR gene polymorphisms (Bsml, Apal, Taql) and PD susceptibility. We performed a systematic literature search for articles published up to February 2014 in multiple databases and selected seven eligible studies.

Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs.

Evaluation of subchronic toxicity of GRD081, a dual PI3K/mTOR inhibitor, after 28-day repeated oral administration in Sprague-Dawley rats and beagle dogs.

GRD081, a newly developed dual PI3K/mTOR inhibitor, is now being considered for evaluation in phase I clinical trial. In this work, the subchronic toxicity of GRD081 in Sprague-Dawley (SD) rats and beagle dogs has been characterized. Rats and dogs received GRD081 orally (2, 5, 10 and 1, 2, 4 mg/kg/day, respectively) on a consecutive daily dosing schedule for 28 days following a 14 days of recovery period.

Subchronic safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis stimulating agent, after 5-week subcutaneous injection in Cynomolgus monkeys and Sprague-Dawley rats.

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is coupled to polyethylene glycol (PEG) and designed to specifically bind and activate the erythropoietin (EPO) receptor to result in production of red blood cells. This study was designed to evaluate the potential subchronic toxicity of EPO-018B for Cynomolgus monkeys and Sprague-Dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys.

Myocilin polymorphisms and primary open-angle glaucoma: a systematic review and meta-analysis.

Background: Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations.

Intraocular pressure-lowering effects of commonly used fixed-combination drugs with timolol: a systematic review and meta-analysis.

Background: The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP), and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol.

Synergetic toxicity of DATR, a recombinant soluble human TRAIL mutant, in combination with traditional chemotherapeutics in rats.

The recombinant soluble human TRAIL mutant (DATR), derived from tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a promising agent for cancer therapy. The present study evaluated the synergetic toxicity of DATR in combination with traditional chemotherapeutics, including irinotecan, polyene paclitaxel and oxaliplatin in rats. Rats treated with polyene paclitaxel alone or in combination with DATR showed severe diarrhea, appetite inhibition, increasing sodium (Na(+)), potassium (Cl(-)) and glucose (GLU) and serious disorders in the haematological system.