Increased connexin 43 expression improves the migratory and proliferative ability of H9c2 cells by Wnt-3a overexpression

The change of connexin 43 (Cx43) expression and the biological behaviors of Cx43 in rat heart cell line H9c2, expressing Wnt-3a (wingless-type MMTV integration site family, member 3A) were evaluated in the present study. Plasmid pcDNA3.1/Wnt-3a was constructed and transferred into H9c2 cells. The cell model Wnt-3a~ -H9c2 steadily expressing Wnt-3a was obtained. Compared with H9c2 and pcDNA3.1-H9c2 cells, the expression of Cx43 in Wnt-3a~ -H9c2 cells was clearly increased, the proliferation of Wnt-3a~ -H9c2 cells was significantly changed, and cell migration abilities were also improved (P<0.05). In comparison with H9c2 and pcDNA3.1-H9c2 cells, the G_2 phase of the cell cycle increased by 11% in Wnt-3a~ -H9c2 cells. Thus, Wnt-3a overexpression is associated with an increase in Cx43 expression and altered migratory and proliferative activity in H9c2 cells. Cx43 might be one of the downstream target genes regulated by Wnt-3a.     

Chinese expert consensus statement on the diagnosis and treatment of fulminant myocarditis

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock,with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial(NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time,we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes(i) mechanical life support(applications of mechanical respirators and circulatory support systems,including intraaortic balloon pump and extracorporeal membrane oxygenation),(ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and(iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.     

Structure elucidation and sulfated derivatives preparation of two alpha-D-glucans from Gastrodia elata Bl. and their anti-dengue virus bioactivities

The structures of two glucans, WGEW and AGEW, isolated from Gastrodia elata Bl. were elucidated using monosaccharide composition analysis by gas chromatography (GC), methylation analysis by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Their structures were deduced as an alpha-D-(1-->4)-glucan with an alpha-(1-->4) linked branch attached to O-6 branch points with different branch degrees. Their sulfate derivatives with distinct degrees of substitution (DS) were prepared. The substitution position was assigned to O-6 according to the (13)C NMR spectra. All sulfated derivatives showed strong anti-dengue virus bioactivities. The structure-activity relationships (SAR) between the polysaccharides and their sulfated derivatives were also investigated. Results showed that the higher the DS is, the more potent the impact on the dengue virus infection would be.     

Genome Identification and Expression Profiles in Response to Nitrogen Treatment Analysis of the Class I CCoAOMT Gene Family in Populus

Biochemical Genetics - Lignin is essential for the characteristics and quality of timber. Nitrogen has significant effects on lignin contents in plants. Nitrogen has been found to affect wood...     

Spontaneous colitis in IL‐10‐deficient mice was ameliorated via inhibiting glutaminase1

Immunity imbalance and barrier damage in the intestinal mucosa are the main pathogenic factors of Crohn's disease (CD). Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide (BPTES) is a glutaminase 1 (Gls1) inhibitor with the dual functions of increasing glutamine levels and immune regulation. In this study, we focused on the role of BPTES in CD‐like enteritis and the possible mechanisms. We found that Gls1 expression was significantly increased in CD intestinal tissue compared with control tissue. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment significantly ameliorated chronic colitis in the IL‐10^?/?, as manifested by decreased disease activity index, body weight change, histological inflammatory degree and inflammatory cytokine expression. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment exerted protective effects on CD that were associated with the maintenance of intestinal barrier integrity and the Th/Treg balance. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment may act in part through TCR‐mediated mammalian target of rapamycin complex 1 (mTORC1) signalling activation. In conclusion, inhibition of Gls1 expression attenuated chronic colitis by maintaining intestinal barrier integrity and the Th/Treg balance, thereby ameliorating CD‐like colitis.     

miR-638 Regulates Differentiation and Proliferation in Leukemic Cells by Targeting Cyclin-dependent Kinase 2

MicroRNAs have been extensively studied as regulators of hematopoiesis and leukemogenesis. We identified miR-638 as a novel regulator in myeloid differentiation and proliferation of leukemic cells. We found that miR-638 was developmentally up-regulated in cells of myeloid but not lymphoid lineage. Furthermore, significant miR-638 down-regulation was observed in primary acute myeloid leukemia (AML) blasts, whereas miR-638 expression was dramatically up-regulated in primary AML blasts and leukemic cell lines undergoing forced myeloid differentiation. These observations suggest that miR-638 might play a role in myeloid differentiation, and its dysregulation may contribute to leukemogenesis. Indeed, ectopic expression of miR-638 promoted phorbol 12-myristate 13-acetate- or all-trans-retinoic acid-induced differentiation of leukemic cell lines and primary AML blasts, whereas miR-638 inhibition caused an opposite phenotype. Consistently, miR-638 overexpression induced G₁ cell cycle arrest and reduced colony formation in soft agar. Cyclin-dependent kinase 2 (CDK2) was found to be a target gene of miR-638. CDK2 inhibition phenotypically mimicked the overexpression of miR-638. Moreover, forced expression of CDK2 restored the proliferation and the colony-forming ability inhibited by miR-638. Our data suggest that miR-638 regulates proliferation and myeloid differentiation by targeting CDK2 and may serve as a novel target for leukemia therapy or marker for AML diagnosis and prognosis.     

Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

Objective

To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD).

Methods

Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed.

Results

(1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE₂ level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE₂ level in PD group.

Conclusions

PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.