Cancer spheroids derived exosomes reveal more molecular features relevant to progressed cancer

Cancer cell spheroids have been shown to be more physiologically relevant to native tumor tissue than monolayer 2D culture cells. Due to enhanced intercellular communications among cells in spheroids, spheroid secreted exosomes which account for transcellular transportation should exceed those from 2D cell culture and may display a different expression pattern of miRNA or protein. To test this, we employed a widely used pancreatic cancer cell line, PANC-1, to create 3D spheroids and compared exosomes generated by both 2D cell culture and 3D PANC-1 spheroids. We further measured and compared exosomal miRNA and GPC-1 protein expression with qRT-PCR and enzyme-linked immunosorbent assay, respectively. It showed that PANC-1 cells cultured in 3D spheroids can produce significantly more exosomes than PANC-1 2D cells and exosomal miRNA and GPC-1 expression derived from spheroids show more features relevant to the progression of pancreatic cancer. These findings point to the potential importance of using spheroids as in vitro model to study cancer development and progression.     

实时定量PCR构建法夫酵母内参基因β-actin、 gpd、18S rRNA标准品质粒和标准曲线

为建立检测法夫酵母JMU-MVP14中虾青素合成相关基因在不同生长时期表达水平的实时定量PCR方法,构建法夫酵母JMU-MVP14的管家基因β-actin、gpd、18S rRNA的标准质粒,进行实时定量PCR,制作标准曲线及回归方程.β-actin基因标准曲线相关系数（R2）=0.9956,扩增效率（E） =96.93％;gpd基因标准曲线相关系数（R2） =0.9901,扩增效率（E） =93.78％;18S rRNA基因标准曲线相关系数（R2） =0.9981,扩增效率（E）=98.76％.3个基因片段的熔解曲线均呈单峰;扩增曲线呈典型的S型动力学曲线,指数期和平台期明显,为理想的熔解曲线和扩增曲线.用geNorm软件对三个管家基因的稳定性进行分析,三个基因的稳定性排序为β-actin＞ 18S rRNA＞ gpd,故β-actin和18S rRNA较适合作为研究法夫酵母JMU-MVP14定量实验的内参基因.     

Commensal bacteria‐dependent select expression of CXCL2 contributes to periodontal tissue homeostasis

The oral and intestinal host tissues both carry a heavy microbial burden. Although commensal bacteria contribute to healthy intestinal tissue structure and function, their contribution to oral health is poorly understood. A crucial component of periodontal health is the recruitment of neutrophils to periodontal tissue. To elucidate this process, gingival tissues of specific‐pathogen‐free and germ‐free wild‐type mice and CXCR2KO and MyD88KO mice were examined for quantitative analysis of neutrophils and CXCR2 chemoattractants (CXCL1, CXCL2). We show that the recruitment ofneutrophils to the gingival tissue does not require commensal bacterial colonization but is entirely dependent on CXCR2 expression. Strikingly, however, commensal bacteria selectively upregulate the expression of CXCL2, but not CXCL1, in a MyD88‐dependent way that correlates with increased neutrophil recruitment as compared with germ‐free conditions. This is the first evidence that the selective use of chemokine receptor ligands contributes to neutrophil homing to healthy periodontal tissue.     

Association between Ambient Temperature and Blood Pressure and Blood Pressure Regulators: 1831 Hypertensive Patients Followed Up for Three Years

Several studies have suggested an association between ambient air temperature and blood pressure. However, this has not been reliably confirmed by longitudinal studies. Also, whether the reaction to temperature stimulation is modified by other factors such as antihypertensive medication is rarely investigated. The present study explores the relationship between ambient temperature and blood pressure, without and with antihypertensive medication, in a study of 1,831 hypertensive patients followed up for three years, in two or four weekly check ups, accumulating 62,452 follow-up records. Both baseline and follow-up blood pressure showed an inverse association with ambient temperature, which explained 32.4% and 65.6% of variation of systolic blood pressure and diastolic blood pressure (P<0.05) respectively. The amplitude of individual blood pressure fluctuation with temperature throughout a year (a 29 degrees centigrade range) was 9.4/7.3 mmHg. Medication with angiotensin converting enzyme inhibitor benazepril attenuated the blood pressure fluctuation by 2.4/1.3 mmHg each year, though the inverse association of temperature and blood pressure remained. Gender, drinking behavior and body mass index were also found to modify the association between temperature and diastolic blood pressure. The results indicate that ambient temperature may negatively regulate blood pressure. Hypertensive patients should monitor and treat blood pressure more carefully in cold days, and it could be especially important for the males, thinner people and drinkers.     

Impact of Functional Constipation on Health-Related Quality of Life in Preschool Children and Their Families in Xi’an,China

Aim

Functional constipation (FC) is one of the common diseases among children. The aim of this study was to investigate the health-related quality of life (HRQOL) in preschool children diagnosed with FC and the impact of the condition on affected families.

Methods

In this cross-sectional, case-control study, 152 children aged 3–6 years with FC, 176 healthy children aged 3–6 years without FC, and their primary caregivers were selected. Chinese versions of the PedsQL^TM 4.0 Generic Core Scale and the Family Impact Module (FIM) were used to assess childhood HRQOL and the impact of FC on family members, respectively. HRQOL scores were compared between children with FC and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, duration and symptoms of FC, as independent variables, was used to determine factors that influenced HRQOL in children and had impacted caregivers.

Results

Scores of physical, emotional, social and school functions, and summary scales were significantly lower in children with FC than in healthy children (p < 0.05). Physical, emotional, social, cognitive, and communication scores for caregivers, as well as daily activities and relationships for families of children with FC, were significantly lower than those of caregivers and families with healthy children (p < 0.05). Children’s ages, duration of FC, symptoms of FC, the child-caregiver relationship, family economic status, and caregiver education level emerged as the main factors influencing HRQOL in children, caregivers, and family members.

Conclusions

FC had a significant impact on HRQOL of affected children and their caregivers, as well as their family functions. Social characteristics of children and caregivers, duration and symptoms of FC and family economic status significantly affected HRQOL of children and caregivers, as well as family functions of children with FC.     

Polymorphisms of Genes in Neurotransmitter Systems Were Associated with Alcohol Use Disorders in a Tibetan Population

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.     

Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis

1. Download : Download high-res image (313KB)
2. Download : Download full-size image

Highlights? Wnt inhibitor sFRP3 exhibits activity-dependent expression in the adult hippocampus ? sFRP3 maintains quiescence of adult hippocampal radial glia-like neural stem cells ? sFRP3 inhibits maturation, dendritic development, and spinal formation of new neurons ? sFRP3 partially mediates activity-dependent adult hippocampal neurogenesis     

Functional Recovery of Denervated Skeletal Muscle with Sensory or Mixed Nerve Protection: A Pilot Study

Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.     

基于2A肽策略构建多基因表达载体的研究进展

多基因表达载体的构建在生物技术领域尤其是基因治疗方面显得日趋重要。目前常用的多基因表达载体多存在载体容量小、上下游基因表达失衡、蛋白活性低或蛋白空间位置不理想等缺陷。2A肽是近年使用较多的一种构建多基因载体的工具,与其它多基因构建策略相比,2A肽策略具有更明显优势。就(类)2A肽的来源、剪切机制、生物学特征、与蛋白定位的关系以及应用方面做一综述。