[Intrinsic and extrinsic mechanisms regulating neuronal dendrite morphogenesis].

Neurons are the structural and functional unit of the nervous system. Precisely regulated dendrite morphogenesis is the basis of neural circuit assembly. Numerous studies have been conducted to explore the regulatory mechanisms of dendritic morphogenesis. According to their action regions, we divide them into two categories: the intrinsic and extrinsic regulators of neuronal dendritic morphogenesis. Intrinsic factors are cell type-specific transcription factors, actin polymerization or depolymerization regulators and regulators of the secretion or endocytic pathways. These intrinsic factors are produced by neuron itself and play an important role in regulating the development of dendrites. The extrinsic regulators are either secreted proteins or transmembrane domain containing cell adhesion molecules. They often form receptor-ligand pairs to mediate attractive or repulsive dendritic guidance. In this review, we summarize recent findings on the intrinsic and external molecular mechanisms of dendrite morphogenesis from multiple model organisms, including Caenorhabditis elegans, Drosophila and mice. These studies will provide a better understanding on how defective dendrite development and maintenance are associated with neurological diseases.

Cohort profile: China National Human Biomonitoring (CNHBM)-A nationally representative, prospective cohort in Chinese population.

OBJECTIVE: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. METHODS: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion. RESULTS: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. CONCLUSIONS: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

Inhibition of long non-coding RNA MALAT1 elevates microRNA-429 to suppress the progression of hypopharyngeal squamous cell carcinoma by reducing ZEB1.

OBJECTIVE: Hypopharyngeal squamous cell carcinoma (HSCC) is a common type of malignant tumor. Long non-coding RNAs (lncRNAs) are known to participate in HSCC development, while the role of lncRNA MALAT1 in HSCC remains largely unknown. We aimed to explore function of the lncRNA MALAT1/miR-429/ZEB1 axis in HSCC progression. METHODS: Levels of MALAT1, miR-429 and ZEB1 in HSCC tissues samples were assessed. The FaDu cells were respectively treated with relative sequence or plasmid of MALAT1, miR-429, or ZEB1. Then, CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were used to determine the cell proliferation, apoptosis, cell cycle, migration and invasion of the cells. The PI3K/Akt/mTOR signaling pathway-related proteins, proliferation-related proteins, cell cycle-related proteins, apoptosis-related proteins, and migration-related proteins were detected using Western blot analysis. The cell growth in vivo was observed. The targeting relationships between MALAT1 and miR-429, and between miR-429 and ZEB1 were confirmed. RESULTS: MALAT1 and ZEB1 expression in HSCC was upregulated while miR-429 expression was downregulated. Reduced MALAT1 and ZEB1, and upregulated miR-429 inactivated the PI3K/Akt/mTOR signaling pathway, suppressed in vitro viability, colony formation ability, migration and invasion, as well as cell growth in vivo, and promoted the apoptosis of FaDu cells. Downregulated miR-429 reversed the role of MALAT1 inhibition in FaDu cell growth. LncRNA MALAT1 served as a sponge of miR-429, thus regulating ZEB1 expression. CONCLUSION: Inhibition of MALAT1 was able to elevate miR-429 to suppress the progression of HSCC via reducing ZEB1. Our research provided a potential therapeutic target for HSCC.