Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase.

The enzymes 3-methylcrotonyl-coenzyme A (CoA) carboxylase (MCC), pyruvate carboxylase and propionyl-CoA carboxylase belong to the biotin-dependent carboxylase family located in mitochondria. They participate in various metabolic pathways in human such as amino acid metabolism and tricarboxylic acid cycle. Many human diseases are caused by mutations in those enzymes but their structures have not been fully resolved so far.

Structure of the intact Tom20 receptor in the human translocase of the outer membrane complex.

The translocase of the outer membrane (TOM) complex serves as the main gate for preproteins entering mitochondria and thus plays a pivotal role in sustaining mitochondrial stability. Precursor proteins, featuring amino-terminal targeting signals (presequences) or internal targeting signals, are recognized by the TOM complex receptors Tom20, Tom22, and Tom70, and then translocated into mitochondria through Tom40. By using chemical cross-linking to stabilize Tom20 in the TOM complex, this study unveils the structure of the human TOM holo complex, encompassing the intact Tom20 component, at a resolution of approximately 6 Å by cryo-electron microscopy.

Structural and functional insights into macrophage migration inhibitory factor from Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum. As an irreplaceable prerequisite in the transmission and prevalence of schistosomiasis japonica, an in-depth study of this obligate host-parasite interaction can provide glimpse into the molecular events in the competition between schistosome infectivity and snail immune resistance. In previous studies, we identified a macrophage migration inhibitory factor (MIF) from O.

Association analysis between SNPs in LATS1 and LATS2 and non-cardia gastric cancer.

Background: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori (H. pylori) infection as well as the risk of non-cardia GC.

Polymorphisms of gene are associated with a decreased risk of infection in a Chinese population.

Background: A series of evidence suggests that genetic variation in toll-like receptor (TLR) 9 might influence the outcome of Helicobacter pylori () infection and play an important role in gastric carcinogenesis.

Methods: We conducted a case-control study to evaluate TLR9 polymorphisms on the risk of infection and non-cardia gastric cancer (GC) in a Chinese population. We genotyped a tagging single-nucleotide polymorphism (SNP), rs164640, and a potentially functional SNP, rs187084, by TaqMan technique among 288 patients with non-cardia GC and 281 controls.

Discovery of Potent EV71 Capsid Inhibitors for Treatment of HFMD.

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. The viral caspid protein VP1 is a well-known target for antiviral efficacy because its occupancy by suitable compounds could stabilize the virus capsid, thus preventing uncoating of virus for RNA release. In this Letter, design, synthesis, and biological evaluation of novel anti-EV71 agents (aminopyridyl 1,2,5-thiadiazolidine 1,1-dioxides) are described.

Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation.

Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the κB element.

Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.

Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds.

Identification and analysis of microRNAs in the left ventricular myocardium of two-kidney one-clip hypertensive rats.

MicroRNAs (miRNAs) are involved in the regulation of numerous physiological and pathological processes. However, little information is available with regard to miRNAs in the left ventricular myocardium of the renovascular angiotensin-dependent hypertensive rat. In this study, miRNA expression profiles in the left ventricular myocardium of two-kidney one-clip (2K1C) hypertensive rats were analyzed using a microarray.

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer.

Aim: To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and p53 in the detection of gastric precancerous lesions.

Methods: Ninety-five patients who were treated for abdominal discomfort, abdominal pain, bloating, and acid reflux at our hospital from January 2010 to December 2011 were included in the study. An ordinary gastroscopic procedure was initially performed to select the lesions.