Survivin as a Target for Anti-cancer Phytochemicals According to the Molecular Docking Analysis

International Journal of Peptide Research and Therapeutics - Survivin is a unique member of the inhibitor of apoptosis protein family. Research has approved Survivin’s ability to interact...     

Streptomyces luteolifulvus sp. nov., a novel actinomycete isolated from soil in Nanjing,China

During the investigation of exploring potential sources of novel species and natural bioactives, a novel actinomycete, designated strain HIT-DPA4^T, was isolated from a soil sample, which was collected from Nanjing, Jiangsu Province, PR China and characterized using a polyphasic approach. On the basis of 16S rRNA gene sequence similarities and the result of phylogenetic analysis, strain HIT-DPA4^T was most closely related to Streptomyces cyaneus CGMCC 4.1671 ^T, and shared the highest sequence similarity of 98.76%. In addition, the cell walls of the species HIT-DPA4^T contained LL-diaminopimelic acid as the diagnostic diamino acid and the whole-cell hydrolysates were identified as glucose and ribose, and the principal phospholipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside and phosphatidylmonomethylethanolamine. MK-9(H₆) and MK-9(H₄) were predominant menaquinones; and C_16:0, anteiso-C_15:0 and C_15:0 as major cellular fatty acids of the organism HIT-DPA4^T. Gene Ontology database analysis and antiSMASH server predicted results displayed that strain HIT-DPA4^T was a promising classification units, which has various types of functions and contains multiple biosynthetic gene clusters with the similarity more than 80%. Multilocus sequence analysis (MLSA) of five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) illustrated that Streptomyces luteolifulvus formed a separate branch in the genus Streptomyces. However, a combination of low level of DNA-DNA relatedness and physiological properties indicated that strain HIT-DPA4^T can be distinguished from its phylogenetically related species Streptomyces cyaneus CGMCC 4.1671 ^T. Moreover, gene synteny research could be further differed organism HIT-DPA4^T from similarity species. Therefore, the strain is concluded to represent a novel species of the genus Streptomyces, for which the name Streptomyces luteolifulvus sp. nov. is proposed. The type strain is HIT-DPA4^T (=?CGMCC 4.7558 ^T?=?TISTR 2751 ^T).

     

Urban and Rural Differences of Acute Cardiovascular Disease Events: A Study from the Population-Based Real-Time Surveillance System in Zhejiang,China in 2012

Zhejiang province, China, has implemented a population based, real-time surveillance system that tracks acute cardiovascular diseases (CVDs) events since 2001. This study aimed to describe the system and report CVD incidence, mortality and case-fatality between urban and rural areas in Zhejiang in 2012. The surveillance system employs a stratified random sampling method covering all permanent residents of 30 counties/districts in Zhejiang. Acute CVD events such as coronary heart disease (CHD) and stroke were defined, registered and reviewed based on the adapted MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) definitions. Data were collected from health facilities, vital registries, supplementary surveys, and additional investigations, and were checked for data quality before input in the system. We calculated the rates and compared them by gender, age and region. In 2012, the incidence, mortality and case-fatality of total acute CVD events were 367.0 (CHD 59.1, stroke 307.9), 127.1 (CHD 43.3, stroke 83.8) per 100,000 and 34.6% (CHD 73.2%, stroke 27.2%), respectively. Compared with rural areas, urban areas reported higher incidence and mortality but lower case-fatality rates for CHD (P<0.001), while lower incidence but higher mortality and case-fatality rates for stroke (P<0.001). We found significant differences on CHD and stroke epidemics between urban and rural areas in Zhejiang. Special attentions need to be given to stroke control, especially in rural areas.     

Dopamine D3 receptor signaling alleviates mouse rheumatoid arthritis by promoting Toll-like receptor 4 degradation in mast cells

Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.Subject terms: Immunological disorders, Rheumatic diseases     

RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism

Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1⁺ MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment.     

Effect of a therapeutic lifestyle change diet on immune functions of moderately hypercholesterolemic humans

Hypercholesterolemia is a risk factor for coronary heart disease (CHD) and also could contribute to impaired immune response. The National Cholesterol Education Program Expert Panel recommends a therapeutic lifestyle change (TLC) diet to reduce the risk for CHD. We investigated the effects of changing from a high-fat Western diet to a low-fat diet in accordance with a TLC diet on immune functions of older adults with hypercholesterolemia to determine whether improving the lipid profile via dietary intervention would have beneficial effects on immune functions. In a double-blind study, 18 subjects consumed both a Western diet (38% fat) and a TLC diet (28% fat) for 32 days in a randomized order. Measures of cellular immune responses, including delayed-type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and interleukin (IL)-2 production, and production of proinflammatory mediators, including tumor necrosis factor-alpha, IL-6, IL-1beta, and prostaglandin E2, were determined. DTH response and lymphocyte proliferative response increased significantly (29% and 27%, respectively) after consumption of a TLC diet. Our results indicate that consumption of a TLC diet enhances T cell-mediated immune functions in older adults with elevated cholesterol level. This might be a clinically important benefit, considering the decline of T cell-mediated immune functions with aging and evidence of impaired immune function associated with hypercholesterolemia.     

The Arabidopsis gene PEPINO/PASTICCINO2 is required for proliferation control of meristematic and non-meristematic cells and encodes a putative anti-phosphatase

Growth in organisms requires that cell division versus differentiation are precisely controlled and that cells, once differentiated, do not resume proliferation activity. Mutants of the Arabidopsis gene PEPINO/PASTICCINO2 develop abnormal shoot phenotypes from slow tumour-like cell proliferation. Abnormal proliferation is enhanced in a mutant background, which elevates endogenous cytokinin levels as seen in double mutants of pepino and altered meristem primordia1. The enlarged shoot apical meristem produces supernumerary abnormal leaves. However, comparison of expression patterns of Cyclin1At and the homeobox gene KNAT2 indicates that PEPINO ( PEP) is involved in cell cycle regulation of meristematic and non-meristematic cells. PEP encodes a putative anti-phosphatase, a representative of an enigmatic class of proteins, which might participate in proliferation processes. In mammals at least two proteins, Sbf1 and STYX, have been predicted to represent functional anti-phosphatases controlling cell proliferation. However, the in vivo function of this class of molecules is not known since no loss-of-function mutants have been reported to date. Anti-phosphatases display a natural change of the essential cysteine by glycine in the phosphatase catalytic signature motif HCxxGxxR(S/T). The remaining motif harbours highly conserved amino acid residues and is thought to constitute a pocket that enables such proteins to bind but not catalyse phosphorylated residues. One of the sequenced mutations in PEP indicates that the integrity of this anti-phosphatase signature motif is essential for function. The analysis of pepino, the first known loss-of-function mutant of an anti-phosphatase in a multicellular organism, proves the biological significance of these molecules.