Role of the ERK1/2 Signaling Pathway in Osteogenesis of Rat Tendon-Derived Stem Cells in Normoxic and Hypoxic Cultures

Background: Ectopic ossification and increased vascularization are two common phenomena in the chronic tendinopathic tendon. The increased vascularization usually leads to an elevated local oxygen tension which is one of micro-environments that can influence differentiate status of stem cells.Objective: This study aimed to investigate the osteogenesis capacity of rat tendon-derived stem cells TDSCs (rTDSCs) in normoxic and hypoxic cultures, and to study the role of ERK1/2 signaling pathway in this process.Methods: rTDSCs were subjected to osteogenesis inductive culture in hypoxic (3% O₂) and normoxic (20% O₂) conditions. The inhibitor U0126 was added along with culture medium to determine the role of ERK1/2 signaling pathway. Cell viability, cell proliferation, alizarin red staining, alkaline phosphatase (AKP) activity, gene expression (ALP, osteocalcin, collagen I and RUNX2) and protein expression (p-ERK1/2 and RUNX2) of osteogenic-cultured rTSDCs were analyzed in this study.Results: Hypoxic and normoxic culture had no effects on cell viability of rTDSCs, whereas the proliferation potential of rTDSCs was significantly increased in hypoxic culture. The osteogenesis capacity of rTDSCs in normoxic culture was significantly promoted compared with hypoxic culture, which was reflected by an increased alizarin red staining intensity, an elevated ALP activity, and the up-regulated gene (ALP, osteocalcin, collagen I and RUNX2) or protein (RUNX2) expression of osteogenic makers. However, the osteogenesis capacity of rTDSCs in both hypoxic and normoxic cultures was attenuated by the inhibitor U0126.Conclusion: Normoxic culture promotes osteogenic differentiation of rTDSCs compared with the hypoxic culture, and the ERK1/2 signaling pathway is involved in this process.     

怀化市2015年5岁以下儿童死亡因素分析

目的了解湖南省怀化市5岁以下儿童死亡情况,提出针对性的干预措施,降低儿童死亡率。方法对怀化市2015年的5岁以下儿童死亡进行监测,根据《儿童死亡监测死因分类说明》进行死因分类,对监测数据进行整理和统计分析。结果 5岁以下儿童死亡率8.04‰,婴儿死亡占5岁以下儿童死亡的72.16%,农村儿童占93.61%。5岁以下儿童死亡率农村(8.56‰)高于城市(4.29‰),春夏季5岁以下儿童死亡率(7.09‰)低于秋冬季(8.96‰),差异均有统计学意义(P<0.05)。5岁以下儿童前5位的死因依次为肺炎、先天性心脏病、意外窒息、早产低体重、溺水。结论怀化市5岁以下儿童死亡控制重点在农村,建议加强孕产期保健服务指导,完善出生缺陷三级预防体系,重视儿童意外伤害防治。     

In vitro cytotoxic activity of isolated compounds from Malaysian <Emphasis Type="Italic">Calophyllum</Emphasis> species

Cancer is a leading cause of death worldwide. In our continuing search for new anticancer agents, four Malaysian Calophyllum species, namely C. castaneum, C. teysmannii, C. canum, and C. sclerophyllum, had been phytochemically studied to give compounds 1–12. All the isolated compounds were evaluated for their antiproliferative activity against nasopharyngeal (SUNE1, TW01, CNE1, HK1) and breast (HCC38, MDA-MB-231, MDA-MB-468, SKBR3) cancer cell lines via methyl thiazolyl tetrazolium cell viability assay. Among the tested compounds, isodispar B (1) showed a promising dose-dependent and a broad spectrum of cytotoxic effects on all the tested cancer cell lines; in particular, potent inhibitory activities were observed on nasopharyngeal cancer cell lines (SUNE1, TW01, CNE1, HK1), with IC₅₀ values ranging from 3.8 to 11.5 µM. In comparison with 5-fluorouracil as positive control, compound 1 was found to exhibit at least sixfold much higher activity than the standard drug used against the nasopharyngeal cell lines. Compound 1 was later found to induce apoptotic cell death in nasopharyngeal cancer cells, as evidenced by ‘Cell Death Detection’ ELISA^PLUS kit, and exhibited good cancer-specific cytotoxicity when tested with noncancerous NP460 cells. Meanwhile, compounds 2–12 displayed moderate to weak activities against the tested cancer cell lines. The findings have highlighted the therapeutic potential of compound 1 against nasopharyngeal cancer.     

Ongoing change of severe hand,foot, and mouth disease pathogens in Yunnan,China, 2012 to 2016

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses (EVs). In this study, a total of 341 children with serious HFMD were admitted to a pediatric hospital in Yunnan, China in 2012 to 2016. EVs were detected in 283 specimens (83.0%) and were assigned to 17 EV types. Enterovirus A71 (EV-A71) was predominant, accounting for 41.6%, and was followed by coxsackievirus A16 (CV-A16; 18.8%), CV-A6 (9.1%), CV-A10 and E-9 (2.9%), CV-B5 (1.8%), CV-A9 (1.2%), E-30 (0.9%), E-18, CV-A4, C-B3, and CV-A2 (0.6%) and other EV types such as CV-A8, CV-A14, E-14, E-11, and CV-B4 (0.3%). All of the EV-A71 isolates belonged to C4a; the CV-A16 belonged to B1b or B1a, although the B1b strains were predominant; and CV-A6 belonged to D3. In 2012 to 2014, E-9 was the third most frequent serotype (8.2%, 5.0%, and 6.5%, respectively). E-9 was not detected in 2015 and 2016. CV-A6 was not detected in 2012 but was the second most frequent serotype (25.3%) in 2015. Active etiological surveillance of HFMD makes it necessary to be aware of these emerging pathogens.     

Neuropsychiatric Disorders in Dementia: Mechanisms of Development and Approaches to Correction

Neuroscience and Behavioral Physiology - Dementia is often combined with other mental disorders which can manifest at different stages of the disease. The severity and rate of progression of these...     

MiR-19a mediates the negative regulation of the NF-κB pathway in lipopolysaccharide-induced endometritis by targeting TBK1

Objective

In both humans and animals, endometritis is severe inflammation of the uterus, and it causes great economic losses in dairy cow production. MicroRNAs have been reported to play an important role in various inflammatory diseases. However, the regulatory mechanisms of miR-19a in endometritis remain unclear. Thus, the aims of this study are to investigate the role of miR-19a in a mouse model of lipopolysaccharide (LPS)-induced endometritis and elucidate the possible mechanisms in bovine endometrial epithelial cells (bEECs).

Methods and results

Histological analysis showed that LPS induced severe pathological changes, suggesting that the endometritis mouse model was well established. The qPCR assay indicated that miR-19a expression in the uterine tissues of mice with endometritis and in bEECs with LPS stimulation was significantly reduced. The overexpression of miR-19a significantly decreased the expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the phosphorylation of NF-κB p65 and IκBα. Similar results were also obtained following the knockdown of TBK1. Furthermore, a dual luciferase reporter assay further validated that miR-19a inhibited TBK1 expression by binding directly to the 3′-UTR of TBK1.

Conclusion

We demonstrated that miR-19a has anti-inflammatory effects and mediates the negative regulation of the NF-κB Pathway in LPS-induced endometritis by targeting TBK1.

     

MMC白蛋白磁性微球的磁响应性能研究

目的：研究自制１－５μｍ的白蛋白磁性药物微球的体内外磁响应性能。方法：用自制的闭合磁场进行体外试验。用放射性同位素Ｉ标记示踪进行动物体内试验,研究２４和４８小时ＥＣＴ显像及脏器的γ计数。结果：在生理盐水中该微球的截留率取决于管径、流速和磁场强度,最大外截留率可达９８％;在外磁场作用下该微球能在颈部很好定位。该微球在肝脏有部分积聚。结论：该微球在体仙外具有良好的磁响应性,而该直径微球本身就具有较好的     

汶川地震中挤压综合征所致急性肾损伤

Objective To identify risk factors associated with the severity of acute kidney injury (AKI) in-duced by crush syndrome and whether the patient required hemodialysis (HD). Method A retrospective study was designed. Within 19 days after the Chinese Wenchuan earthquake (May 12, 2008), 63 victims (33 men, 30women) of 2139 cases were hospitalized at Mianyang Central Hospital (Siehuau, China) because of crush syn-drome caused by crush injuries. The patients with renal dysfimcfion before the earthquake were excluded. Totally 63 patients with AKI associated with crush syndrome were included in this study and were divided into two groups: group 1, 25 patients, requiring HD (when urine volume <250 mL/d;serum potassium> 6 mmol/L) ; and group 2, 38 patients, without HD. The following data were collected retrospectively for all patients: (1) epidemiological parameters: age, gender, race, time under the rubble, liquid treatmem before being rescued; (2) clinical param-eters: blood pressure, body area crushed, amputation, fasciotomy, blood transfusion, quantity of fluid infusion, urine output in the first 24 hours; (3) initial laboratory data: complete blood count, urine analysis, serum chem-istry, arterial blood gas analysis. Comparisons between the two groups were made using SPSS 10.0. The quantita-tive data and categorical data were analyzed using t tests and χ2 tests, respectively. P -values < 0.05 were consid-ered to indicate significant differences. The significant variables were entered into logistic regression models to de-termine the risk factors for the severity of AK1 in patients with crush syndrome and whether the patient required HD. Results Four significant risk factors with P -values < 0.05 were identified: fasciotomy, cystatin C (Cys C)level, myoglobin (MB) level and lactic acidosis. The odds ratios (95% confidence intervals) were 8.641 (3.027～76.479), 6.956 (3.027～76.479), 5.379 (3.027～76.479) and 4.833 (2.569～32.764), respectively. Conclusions In addition to urine output and potassium levels, we found that four risk factors, namely faseiotomy, Cys C and MB levels, and lactic acidosis, were significanfly associated with the severity of AKI and whether the patient required hemodialysis.