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Background and Aims: Low-grade chronic inflammation was reported to serve as a distinctive pathophysiologic feature of coronary artery disease (CAD), the leading cause of death around the world. Herein, the current study aimed to explore whether and how microRNA-34c-5p (miR-34c-5p), a miRNA enriched in extracellular vesicles (EVs) originated from the activated platelet (PLT-EVs), affects the inflammation of human coronary artery endothelial cells (HCAECs).Methods and Results: HCAECs were established as an in vitro cell model using oxidized low-density lipoprotein (ox-LDL). miR-34c-5p, an abundant miRNA in PLT-EVs, can be transferred to HCAECs and target PODXL by binding to its 3'UTR. Gain- and loss-of-function experiments of miR-34c-5p and podocalyxin (PODXL) were performed in ox-LDL-induced HCAECs. Subsequently, HCAECs were subjected to co-culture with PLT-EVs, followed by detection of the expression patterns of key pro-inflammatory factors. Either miR-34c-5p mimic or PLT-EVs harboring miR-34c-5p attenuated the ox-LDL-evoked inflammation in HCAECs by suppressing interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). By blocking the P38 MAPK signaling pathway, miR-34c-5p-mediated depletion of PODXL contributed to protection against ox-LDL-induced inflammation. In vitro findings were further validated by findings observed in ApoE knock-out mice. Additionally, miR-34c-5p in PLT-EVs showed an athero-protective role in the murine model.Conclusion: Altogether, our findings highlighted that miR-34c-5p in PLT-EVs could alleviate inflammation response in HCAECs by targeting PODXL and inactivation of the P38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Estrogen receptors α (ERα) and β (ERβ) show distinct contributions to tumor initiation and progression. Given that ERβ mainly functions as a "tumor suppressor", activation of ERβ using its specific agonist should be able to inhibit tumor progression. In this study, we show that a newly developed ERβ agonist, OSU-ERb-12, can not only impede ovarian cancer cell expansion and tumor growth but also reduce the cancer stem cell (CSC) population. OSU-ERb-12 could inhibit epithelial-to-mesenchymal transition (EMT) in ovarian cancer cells by increasing Snail expression, thereby, blocking EMT-mediated cancer cell dedifferentiation. We also found that OSU-ERb-12 inhibits ovarian cancer expansion in an ERα-independent manner while limiting the CSC population in an ERα-dependent manner. Taken together, our data suggest that the newly developed ERβ agonist OSU-ERb-12 can be used not only to hinder tumor growth but also has the potential to prevent tumor relapse and metastasis by depleting CSCs. Epithelial ovarian cancer is the most lethal malignancy of the female reproductive tract. A healthy ovary expresses both Estrogen Receptor α (ERα) and β (ERβ). Given that ERα is generally considered to promote cell survival and proliferation, thereby, enhancing tumor growth, while ERβ shows a protective effect against the development and progression of tumors, the activation of ERβ by its agonists could be therapeutically beneficial for ovarian cancer. Here, we demonstrate that the activation of ERβ using a newly developed ERβ agonist, OSU-ERb-12, can impede ovarian cancer cell expansion and tumor growth in an ERα-independent manner. More interestingly, we found that OSU-ERb-12 also reduces the cancer stem cell (CSC) population in ovarian cancer by compromising non-CSC-to-CSC conversion. Mechanistically, we revealed that OSU-ERb-12 decreased the expression of Snail, a master regulator of the epithelial-to-mesenchymal transition (EMT), which is associated with de novo CSC generation. Given that ERα can mediate EMT and facilitate maintenance of the CSC subpopulation and that OSU-ERb-12 can block the transactivity of ERα, we conclude that OSU-ERb-12 reduces the CSC subpopulation by inhibiting EMT in an ERα-dependent manner. Taken together, our data indicate that the ERβ agonist OSU-ERb-12 could be used to hinder tumor progression and limit the CSC subpopulation with the potential to prevent tumor relapse and metastasis in patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Human T-cell leukemia virus type I (HTLV-I) has efficiently adapted to its host and establishes a persistent infection characterized by low levels of viral gene expression and slow proliferation of HTLV-I infected cells over decades. We have previously found that HTLV-I p30 is a negative regulator of virus expression. Results In this study we show that p30 targets multiple cell cycle checkpoints resulting in a delayed entry into S phase. We found that p30 binds to cyclin E and CDK2 and prevents the formation of active cyclin E-CDK2 complexes. In turn, this decreases the phosphorylation levels of Rb and prevents the release of E2F and its transcriptional activation of genes required for G1/S transition. Our studies also show that HTLV-II p28 does not bind cyclin E and does not affect cell cycle progression. Conclusions In contrast to HTLV-I, the HTLV-II-related retrovirus is not oncogenic in humans. Here we report that the HTLV-I p30 delays cell cycle progression while its homologue, HTLV-II p28, does not, providing evidence for important differences between these two related retrovirus proteins.

A cytotoxicity study was conducted with a primary culture of the nervous system cells, including brain microvascular endothelial cells (BMECs) and astrocytes, which are important components of the blood-brain barrier. The real-time cell analysis (RTCA) was used to determine the cytotoxicity of copper-oxide nanoparticles (CuO NPs). The IC50 values of CuO NPs in astrocytes and BMECs were determined by the RTCA at different exposure times and were used as base values for further research. DNA damage after exposure to CuO NPs for 3 and 24 h was assessed using comet assay at the IC50 obtained from RTCA. The onset time of cytotoxicity induced by CuO NPs was 2 and 2-4 h post-exposure in BMECs and astrocytes, respectively. Furthermore, the degree of cytotoxicity induced by exposure to CuO NPs for 24-48 h in the BMECs and astrocytes was similar. Treatment with CuO NPs at 1/2*IC50 and 1/5*IC50 for 3 h induced genotoxicity in both cells as assessed by a measurement of DNA damage, although no cytotoxicity was observed. However, significant DNA damage was observed at all concentrations of CuO NPs used in this study, when the treatment time was 24 h. [ABSTRACT FROM AUTHOR]

Objective: To explore TRPV1 UTR-3 polymorphism and susceptibility of childhood asthma of Han Nationality in Beijing., Methods: 177 asthmatics, 44 atopy, and 151 control children less than 14-years-old were enrolled in case-control study, and all subjects were investigated by ISSAC questionnaires. Dominant, recessive, co-dominant, over-dominant, and log additive model were used to do genotype analysis, and LD analysis and haplotypes of SNPs were tested by Haploview 4.1. Hardy-Weinberg equilibrium test, Person chis-square test, linkage disequilibrium analysis, and logistic analysis were performed by SAS 9.1 software to determine the association between polymorphisms of TRPV1 and susceptibility of childhood asthma., Results: Polymorphisms were found in rs402369, rs4790521, and rs4790522, Hardy-Weinberg P > 0.05. As to allele frequencies, frequency of SNP rs4790521 T/C in asthmatics were significantly increased (P < 0.05), no significant difference were found in MAF of rs402369 and rs4790522 (P > 0.05). Genotype analysis showed that rs4790521 C/C and rs4790522 A/C were associated with childhood asthma (P < 0.05), and odd ratios were 2.94 (1.32 - 6.53) and 0.588 (0.376 - 0.920) respectively. LD were found between rs4790521 and rs4790522, 3 haplotypes were built. Adjusted by age, gender, parent asthma history, and smoking exposure, logistic stepwise analysis showed that MAF of rs4790521, allozygote C/C of rs4790521, and haplotype C/C were associated with susceptibility to childhood asthma in Chinese Han Nationality in Beijing (P < 0.05)., Conclusion: TRPV1 UTR-3 polymorphisms could be associated with the susceptibility to childhood asthma of Han Nation a city in Beijing.

Viable but nonculturable state of bacteria means the state of bacteria cannot be cultured in routine media, but is alive and metabolic active. Many bacteria including some pathogens can enter this state and maintain virulence or pathogenicity. In this paper, the information including character, induction factors, resuscitation, detection and hygiene significance about bacteria's viable but nonculturable state was reviewed.

Objective: To assess the safety of four kinds new-type drinking water and explore its effect on immunologic function in mice., Methods: Its acute oral toxicity and Genotoxicity were detected using acute toxicity test, Ames test, micronucleus assay of mice bone marrow cell and mice sperm malformation test. Its effects on cellular, humoral immune function were assessed respectively by metatarsus-thickening method, Jerne-improved slide method., Results: Its acute oral LD50 in mice were greater than 10000mg/kg BW, three genetic toxicity tests showed negative results, the metatarsal injected with SRBC and number of antibody forming cells were no evidently thicker in test group than in control group., Conclusion: The result did not indicate the genotoxicity of the four kinds new-type drinking water and they couldn't effect immunologic function in mice.