Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways

Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS. Consistent findings were obtained in vivo. Additionally, IV inhibited H₂O₂-induced cytotoxicity and apoptosis. However, these effects were partially reversed following the use of an HO-1 inhibitor in vitro. Further studies revealed that IV significantly inhibited MAPK phosphorylation, reduced NF-κB nuclear translocation, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in RAW 264.7 cells. In vivo, pretreatment with IV attenuated histopathological changes, infiltration of polymorphonuclear granulocytes and endothelial activation, decreased the expression of ICAM-1 and VCAM-1, reduced the levels of MPO and MDA, and increased the content of GSH and SOD in ALI. Furthermore, IV treatment effectively increased Nrf2 and HO-1 expression in lung tissues. Therefore, IV may offer a protective role against LPS-induced ALI by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.     

Copy-Number Mutations on Chromosome 17q24.2-q24.3 in Congenital Generalized Hypertrichosis Terminalis with or without Gingival Hyperplasia

Congenital generalized hypertrichosis terminalis (CGHT) is a rare condition characterized by universal excessive growth of pigmented terminal hairs and often accompanied with gingival hyperplasia. In the present study, we describe three Han Chinese families with autosomal-dominant CGHT and a sporadic case with extreme CGHT and gingival hyperplasia. We first did a genome-wide linkage scan in a large four-generation family. Our parametric multipoint linkage analysis revealed a genetic locus for CGHT on chromosome 17q24.2-q24.3. Further two-point linkage and haplotyping with microsatellite markers from the same chromosome region confirmed the genetic mapping and showed in all the families a microdeletion within the critical region that was present in all affected individuals but not in unaffected family members. We then carried out copy-number analysis with the Affymetrix Genome-Wide Human SNP Array 6.0 and detected genomic microdeletions of different sizes and with different breakpoints in the three families. We validated these microdeletions by real-time quantitative PCR and confirmed their perfect cosegregation with the disease phenotype in the three families. In the sporadic case, however, we found a de novo microduplication. Two-color interphase FISH analysis demonstrated that the duplication was inverted. These copy-number variations (CNVs) shared a common genomic region in which CNV is not reported in the public database and was not detected in our 434 unrelated Han Chinese normal controls. Thus, pathogenic copy-number mutations on 17q24.2-q24.3 are responsible for CGHT with or without gingival hyperplasia. Our work identifies CGHT as a genomic disorder.     

Continental Refugium in the Mongolian Plateau during Quaternary Glacial Oscillations: Phylogeography and Niche Modelling of the Endemic Desert Hamster,Phodopus roborovskii

The Mongolian Plateau (MP), which is situated in the interior of Asia and possesses a typical continental climate, experienced harsh climatic conditions during the Quaternary glacial fluctuations. Although these events likely had huge impacts on the local animal populations, the current effects have hardly been explored. To investigate whether the MP supported a refugium along an oceanic-continental gradient (ROCG), and whether this refugium was glacial or interglacial, we investigated the demographic and phylogeographic history of an endemic mammal species, the desert hamster Phodopus roborovskii. We reconstructed the demographic variation, the phylogeographic diffusion, and modelled the potential habitat during historical periods. The genetic diversity in the MP was the highest among all the localities, and the MP was a suitable habitat throughout the modelled historical periods. A phylogeographic diffusion analysis emphasized the importance of the MP as the centre of origin, preservation and spread for P. roborovskii. The homogeneous landscape provided the opportunity for a wide gene flow, which resulted in low resolution of the phylogenetic relationships. Moreover, P. roborovskii was favoured by the interglacial condition, with both its demographical and geographical ranges expanded within the interglacial periods. The range variation from the Last Glacial Maximum to the current condition reflects a distinct longitudinal shift, while both ranges largely contracted from that of the Last Interglacial. Our results support that the MP served as a refugium and spread centre for P. roborovskii during the Quaternary climate fluctuations. The interglacial expansion and the longitudinal shifts highlighted the important effects of precipitations on the distribution range of species adapted to arid and semi-arid during glacial oscillations.     

Comparison of Risk Factor between Lacunar Stroke and Large Artery Atherosclerosis Stroke: A Cross-Sectional Study in China

Background

Stroke is the second most common cause of mortality in China. Although most subtypes of ischemic stroke share similar risk factors, they have different etiologies. Our study aimed to evaluate the different risk factor profiles between the stroke subtypes, lacunar infarcts (LI) and large-artery atherosclerosis (LAA), and clarify the characteristics of current acute ischemic stroke in China.

Methods

In this cross-sectional study, we analyzed the clinical characteristics of 1982 patients with acute ischemic stroke who were admitted to the neurology department at the Peking University First Hospital between 2007 and 2014. Ischemic stroke was further classified into LAA, LI, cardioembolism (CE) and undetermined causes of infarction (UDI) according to TOAST classification. Demographic characteristics, risk factors, as well as the findings of laboratory and imaging tests of 1773 patients with LAA and LI, were analyzed by univariate and multivariate logistic analysis.

Results

Of the 1982 ischemic stroke patients included in this study, 1207 were diagnosed with LAA, 566 with LI, 173 with cardioembolism (CE) and 36 with undetermined causes of infarction (UDI). By comparing the risk factors in multivariate logistic regression analysis, hypertension [odds ratio (OR) = 1.832] and white matter leukoaraiosis (WML) (OR = 1.865) were found to be more strongly correlated with LI than LAA. Low density lipoprotein- cholesterol (LDL-c) (OR = 0.774) were more strongly related to LAA than LI.

Conclusions

This study found that hypertension and WML were more strongly correlated with LI than LAA. LDL-c was more strongly related to LAA than LI.     

Mid- to Long-Term Outcomes of Cervical Disc Arthroplasty versus Anterior Cervical Discectomy and Fusion for Treatment of Symptomatic Cervical Disc Disease: A Systematic Review and Meta-Analysis of Eight Prospective Randomized Controlled Trials

Purpose

This study aimed to investigate the mid- to long-term outcomes of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for the treatment of 1-level or 2-level symptomatic cervical disc disease.

Methods

Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify relevant randomized controlled trials that reported mid- to long-term outcomes (at least 48 months) of CDA versus ACDF. All data were analyzed by Review Manager 5.3 software. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous variables. The weighted mean difference (WMD) and 95%CIs were calculated for continuous variables. A random effect model was used for heterogeneous data; otherwise, a fixed effect model was used.

Results

Eight prospective randomized controlled trials (RCTs) were retrieved in this meta-analysis, including 1317 and 1051 patients in CDA and ACDF groups, respectively. Patients after an ACDF had a significantly lower rate of follow-up than that after CDA. Pooled analysis showed patients in CDA group achieved significantly higher rates of overall success, Neck Disability Index (NDI) success, neurological success and significantly lower rates of implant/surgery-related serious adverse events and secondary procedure compared with that in ACDF group. The long-term functional outcomes (NDI, Visual Analog Scale (VAS) neck and arm pain scores, the Short Form 36 Health Survey physical component score (SF-36 PCS)), patient satisfaction and recommendation, and the incidence of superior adjacent segment degeneration also favored patients in CDA group with statistical difference. Regarding inferior adjacent segment degeneration, patients in CDA group had a lower rate without statistical significance.

Conclusions

This meta-analysis showed that cervical disc arthroplasty was superior over anterior discectomy and fusion for the treatment of symptomatic cervical disc disease in terms of overall success, NDI success, neurological success, implant/surgery-related serious adverse events, secondary procedure, functional outcomes, patient satisfaction and recommendation, and superior adjacent segment degeneration.     

Ferroptosis in Cancer Progression: Role of Noncoding RNAs

Ferroptosis is a novel form of programmed cell death, and it is characterized by iron-dependent oxidative damage, lipid peroxidation and reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence and that abundant ferroptosis in cells can inhibit tumor progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long noncoding RNAs, and circular RNAs, have been shown to be involved in biological processes of ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism of this phenomenon is still unclear. To clarify this issue, increasing studies have focused on the regulatory roles of ncRNAs in the initiation and development of ferroptosis and the role of ferroptosis in progression of various cancers, such as lung, liver, and breast cancers. In this review, we systematically summarized the relationship between ferroptosis-associated ncRNAs and cancer progression. Moreover, additional evidence is needed to identify the role of ferroptosis-related ncRNAs in cancer progression. This review will help us to understand the roles of ncRNAs in ferroptosis and cancer progression and may provide new ideas for exploring novel diagnostic and therapeutic biomarkers for cancer in the future.     

<Emphasis Type="Italic">Arabidopsis</Emphasis> ETO1 specifically interacts with and negatively regulates type 2 1-aminocyclopropane-1-carboxylate synthases

Background  

In Arabidopsis, ETO1 (ETHYLENE-OVERPRODUCER1) is a negative regulator of ethylene evolution by interacting with AtACS5, an isoform of the rate-limiting enzyme, 1-aminocyclopropane-1-carboxylate synthases (ACC synthase or ACS), in ethylene biosynthetic pathway. ETO1 directly inhibits the enzymatic activity of AtACS5. In addition, a specific interaction between ETO1 and AtCUL3, a constituent of a new type of E3 ubiquitin ligase complex, suggests the molecular mechanism in promoting AtACS5 degradation by the proteasome-dependent pathway. Because orthologous sequences to ETO1 are found in many plant species including tomato, we transformed tomato with Arabidopsis ETO1 to evaluate its ability to suppress ethylene production in tomato fruits.     

Nestin Positive Bone Marrow Derived Cells Responded to Injury Mobilize into Peripheral Circulation and Participate in Skin Defect Healing

Exogenously infused mesenchymal stem cells (MSCs) are thought to migrate to injury site through peripheral blood stream and participate in tissue repair. However, whether and how endogenous bone marrow MSCs mobilized to circulating and targeted to tissue injury has raised some controversy, and related studies were restricted by the difficulty of MSCs identifying in vivo. Nestin, a kind of intermediate filament protein initially identified in neuroepithelial stem cells, was recently reported as a credible criteria for MSCs in bone marrow. In this study, we used a green fluorescent protein (GFP) labeled bone marrow replacement model to trace the nestin positive bone marrow derived cells (BMDCs) of skin defected-mice. We found that after skin injured, numbers of nestin⁺ cells in peripheral blood and bone marrow both increased. A remarkable concentration of nestin⁺ BMDCs around skin wound was detected, while few of these cells could be observed in uninjured skin or other organs. This recruitment effect could not be promoted by granulocyte colony-stimulating factor (G-CSF), suggests a different mobilization mechanism from ones G-CSF takes effect on hematopoietic cells. Our results proposed nestin⁺ BMDCs as mobilized candidates in skin injury repair, which provide a new insight of endogenous MSCs therapy.