miR-155 increases stemness and decitabine resistance in triple-negative breast cancer cells by inhibiting TSPAN5.

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24- CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24- CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1.

BACKGROUND: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2',7'-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. RESULTS: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3'UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to 'CUGUUGA' in 3'UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. CONCLUSION: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

[Polymorphs of clopidogrel bisulfate].

This paper is to report the polymorphism of raw materials of clopidogrel bisulfate at home and abroad. By the analysis of Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (p-XRD), samples are roughly classified into two groups, except one patent material. And the differential scanning calorimeter (DSC) examination showed more detailed information for these materials. The results of the study could provide comprehensive basis for the quality evaluation of clopidogrel bisulfate.

SPTBN2 regulates endometroid ovarian cancer cell proliferation, invasion and migration via ITGB4­mediated focal adhesion and ECM receptor signalling pathway.

Ovarian cancer is as a major contributor to gynaecologic death globally. The present study aimed to investigate the regulatory role of spectrin ß non-erythrocytic 2 gene (SPTBN2) in endometroid ovarian cancer and its mechanism of action. According to the Gene Expression Profiling Interactive Analysis (GEPIA) database, SPTBN2 expression is elevated in ovarian cancer tissues and higher SPTBN2 expression indicated a worse prognosis. The present study assessed SPTBN2 mRNA and protein expression levels by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability, proliferation, migration and invasion were assessed with Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays, respectively. SPTBN2 expression was notably enhanced in ovarian cancer cell lines, especially in A2780 cells compared with HOSEPiC cells (P<0.001). Following transfection with small interfering (si)RNA targeting SPTBN2, the viability, proliferation, migration and invasion of A2780 cells were decreased compared with those of A2780 cells transfected with siRNA-NC (P<0.001). Gene Set Enrichment Analysis database revealed that SPTBN2 was primarily enriched in 'focal adhesion' and 'extracellular matrix (ECM)-receptor interaction', whereas SPTBN2 was significantly associated with integrin ß4 (ITGB4) in the GEPIA database. In addition, rescue experiments were performed to determine the mechanism of SPTBN2 in endometroid ovarian cancer. ITGB4 overexpression reversed the inhibitory effects of the SPTBN2 knockdown on viability, proliferation, migration and invasion of A2780 cells (P<0.05). The impacts of SPTBN2 on the expression of focal adhesion and downstream ECM receptor signalling-related proteins, including Src and p-FAK/FAK, were significantly reversed by ITGB4 overexpression (P<0.01). Collectively, SPTBN2 may regulate endometroid ovarian cancer cell proliferation, invasion and migration through the ITGB4-mediated focal adhesion and ECM receptor signalling pathway.

Corrigendum to "Study of hydrosalpinx on endometrial growth and expression of HOXA10mRNA and related factors" [Heliyon 9(6) (June 2023) e17063].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17063.].

Study of hydrosalpinx on endometrial growth and expression of HOXA10mRNA and related factors.

Objective: The objective of the study is to extract the patient's endometrium at the time of proliferative stage using hydrosalpinx in order to culture the cells and decidualization induction in vitro. Further, the study is also intended at identifying the expression of HOXA10mRNA and related factors and understand the hydrosalpinx's impact upon the working mechanism of endometrial cells. Methods: Once the extraction of the primary cells is over, the cells are cultured and other activities are performed such as the cell identification, CCK8 assay, cell decidua induction and HE staining. The researchers assessed the expression levels of HOXA10, IGFBP1 and avß3 in either proliferation or secretion of the endometrium. This was accomplished using Western blot assay and real-time fluorescence quantitative PCR. Results: The results confirmed that at the time of endometrial proliferation, there was a decline in the expression of HOXA10 as a result of tubal effusion influence. This affected its expression in the secretory stage i.e., corresponding function. Further, a significant decline was observed in the levels of HOXA10mRNA of endometrial cells that were subjected to continuous tubal effusion, post decidualization. It was found that during decidualization, if thetubal effusion is removed, it is possible to restore the expression of HOXA10mRNA to a certain extent, though it is not possible to reach the general endometrial level. So, in terms of clinical aspects, the expression of HOxa10 mRNA by the endometrial cells decreases significantly when blocking the hydrosalpinx. Conclusions: Among hydrosalpinx patients, one of the major mechanisms that damage the endometrium was found to be the abnormal expression of HOXA10 followed by IGFBP1 and avß3, its downstream genes. This further results in the implantation of the embryo as well. Though it is possible to gradually repair the damage after the removal of hydrosalpinx, the recovery is a time-consuming process.

Nagimycins A and B, Antibacterial Ansamycin-Related Macrolactams from Streptomyces sp. NA07423.

Chemical investigation of Streptomyces sp. NA07423 led to the discovery of two unreported macrolactams, nagimycins A (1) and B (2). Their structures were elucidated by NMR, HRESIMS, X-ray crystallography, and comparison of experimental and theoretical ECD spectra. The nagimycins have a unique butenolide moiety rarely found in ansamycin antibiotics. Genome analysis revealed the putative biosynthetic gene cluster for nagimycins, and a likely biosynthetic pathway was proposed. Notably, compounds 1 and 2 exhibited potent antibacterial activity against two pathogenic Xanthomonas bacteria.

Long-term Exposure to Ambient PM2.5 and Its Components Associated With Diabetes: Evidence From a Large Population-Based Cohort From China.

OBJECTIVE: Association between particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) components and diabetes remains unclear. We therefore aimed to investigate the associations of long-term exposure to PM2.5 components with diabetes. RESEARCH DESIGN AND METHODS: This study included 69,210 adults with no history of diabetes from a large-scale epidemiologic survey in Southwest China from 2018 to 2019. The annual average concentrations of PM2.5 and its components were estimated using satellite remote sensing and chemical transport modeling. Diabetes was identified as fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or hemoglobin A1c ≥48 mmol/mol (6.5%). The logistic regression model and weighted quantile sum method were used to estimate the associations of single and joint exposure to PM2.5 and its components with diabetes, respectively. RESULTS: Per-SD increases in the 3-year average concentrations of PM2.5 (odds ratio [OR] 1.08, 95% CI 1.01-1.15), black carbon (BC; 1.07, 1.01-1.15), ammonium (1.07, 1.00-1.14), nitrate (1.08, 1.01-1.16), organic matter (OM; 1.09, 1.02-1.16), and soil particles (SOIL; 1.09, 1.02-1.17) were positively associated with diabetes. The associations were stronger in those ≥65 years. Joint exposure to PM2.5 and its components was positively associated with diabetes (OR 1.04, 95% CI 1.01-1.07). The estimated weight of OM was the largest among PM2.5 and its components. CONCLUSIONS: Long-term exposure to BC, nitrate, ammonium, OM, and SOIL is positively associated with diabetes. Moreover, OM might be the most responsible for the relationship between PM2.5 and diabetes. This study adds to the evidence of a PM2.5-diabetes association and suggests controlling sources of OM to curb the burden of PM2.5-related diabetes.

Ambient PM2.5 Components Are Associated With Bone Strength: Evidence From a China Multi-Ethnic Study.

CONTEXT: The relationship between the components of particulate matter with an aerodynamic diameter of 2.5 or less (PM2.5) and bone strength remains unclear. OBJECTIVE: Based on a large-scale epidemiologic survey, we investigated the individual and combined associations of PM2.5 and its components with bone strength. METHODS: A total of 65 906 individuals aged 30 to 79 years were derived from the China Multi-Ethnic Cohort Annual average concentrations of PM2.5 and its components were estimated using satellite remote sensing and chemical transport models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound. The logistic regression model and weighted quantile sum method were used to estimate the associations of single and joint exposure to PM2.5 and its components with QUI, respectively. RESULTS: Our analysis shows that per-SD increase (µg/m3) in 3-year average concentrations of PM2.5 (mean difference [MD] -7.38; 95% CI, -8.35 to -6.41), black carbon (-7.91; -8.90 to -6.92), ammonium (-8.35; -9.37 to -7.34), nitrate (-8.73; -9.80 to -7.66), organic matter (-4.70; -5.77 to -3.64), and soil particles (-5.12; -6.10 to -4.15) were negatively associated with QUI. In addition, these associations were more pronounced in men, and people older than 65 years with a history of smoking and chronic alcohol consumption. CONCLUSION: We found that long-term exposure to PM2.5 and its components may lead to reduced bone strength, suggesting that PM2.5 and its components may potentially increase the risk of osteoporosis and even fracture. Nitrate may be responsible for increasing its risk to a greater extent.

The mediation role of blood lipids on the path from air pollution exposure to MAFLD: A longitudinal cohort study.

BACKGROUND & AIMS: Recent cross-sectional studies found that exposure to ambient air pollution (AP) was associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). The alternation of blood lipids may explain the association, but epidemiological evidence is lacking. We aimed to examine whether and to what extent the association between long-term exposure to AP and incident MAFLD is mediated by blood lipids and dyslipidemia in a prospective cohort. METHODS: We included 6350 participants from the China Multi-Ethnic Cohort (CMEC, baseline 2018-2019, follow-up 2020-2021). Three-year average (2016-2018) of AP (PM1, PM2.5, PM10, NO2), blood lipids (TC, LDL-C, HDL-C, TG with their combinations) and incident MAFLD for each individual were assessed chronologically. Linear and logistic regression was used to assess the associations among AP, blood lipids, and MAFLD, and the potential mediation effects of blood lipids were evaluated using causal mediation analysis. RESULTS: A total of 744 participants were newly diagnosed with MAFLD at follow-up. The odds ratios of MAFLD associated with a 10 µm increase in PM1, PM2.5, and NO2 were 1.35 (95 % CI: 1.14, 1.58), 1.34 (1.10, 1.65) and 1.28 (1.14, 1.44), respectively. Blood lipids are important mediators between AP and incident MAFLD. LDL-C (Proportion Mediated: 6.9 %), non-HDL (13.4 %), HDL-C (20.7 %), LDL/HDL (30.1 %), and dyslipidemia (6.5 %) significantly mediated the association between PM2.5 and MAFLD. For PM1, the indirect effects were similar to those for PM2.5, with a larger value for the direct effect, and the mediation proportion by blood lipids was less for NO2. CONCLUSION: Blood lipids are important mediators between AP and MAFLD, and can explain 5 %-30 % of the association between AP and incident MAFLD, particularly cholesterol-related variables, indicating that AP could lead to MAFLD through the alternation of blood lipids. These findings provided mechanical evidence of AP leading to MAFLD in epidemiological studies.

The Two Classes of Ceramide Synthases Play Different Roles in Plant Immunity and Cell Death.

Ceramide synthases (CSs) produce ceramides from long-chain bases (LCBs). However, how CSs regulate immunity and cell death in Arabidopsis thaliana remains unclear. Here, we decipher the roles of two classes of CS, CSI (LAG1 HOMOLOG 2, LOH2) and CSII (LOH1/3), in these processes. The loh1-2 and loh1-1 loh3-1 mutants were resistant to the bacterial pathogen Pseudomonas syringae pv maculicola (Psm) DG3 and exhibited programmed cell death (PCD), along with increased LCBs and ceramides, at later stages. In loh1-2, the Psm resistance, PCD, and sphingolipid accumulation were mostly suppressed by inactivation of the lipase-like proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and PHYTOALEXIN DEFICIENT 4 (PAD4), and partly suppressed by loss of SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2). The LOH1 inhibitor fumonisin B1 (FB1) triggered EDS1/PAD4-independent LCB accumulation, and EDS1/PAD4-dependent cell death, resistance to Psm, and C16 Cer accumulation. Loss of LOH2 enhances FB1-, and sphinganine-induced PCD, indicating that CSI negatively regulates the signaling triggered by CSII inhibition. Like Cer, LCBs mediate cell death and immunity signaling, partly through the EDS1/PAD4 pathway. Our results show that the two classes of ceramide synthases differentially regulate EDS1/PAD4-dependent PCD and immunity via subtle control of LCBs and Cers in Arabidopsis.

The condensed tannin chemistry and astringency properties of fifteen Vitis davidii Foex grapes and wines.

This study sought to determine the effects of variety on the astringency and chemistry of condensed tannins of spine grapes and wines. Fifteen varieties of red spine grape (Vitis davidii Foex) were used. Condensed tannin content, composition, and wine astringency were determined. The condensed tannin profiles were assessed by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The condensed tannin content highly depended on the variety ranging from 0.30 mg/g to 7.80 mg/g (in skins), from 3.12 mg/g to 8.82 mg/g (in seeds), and from 62.60 mg/L to 225.90 mg/L (in wines). There were significant differences in proportions of certain constitutive subunits (as mole%) and mean degree of polymerization (mDp) among the varieties. Correlation analysis revealed that condensed tannin concentration and composition had a significant effect on the sensory evaluation and quantitative analysis of astringency. A positive correlation between mDp and astringency was also observed. The present results expand knowledge of the characterization of spine grape and wine condensed tannin chemistry and astringency.

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia.

High altitude is an extreme environment that imposes hypoxic pressure on physiological processes, and natives living at high altitudes are more adaptive in certain physiological processes. So far, epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood. Here, we recruit 32 Tibetan elite alpinists (TEAs), who have successfully mounted Everest (8848 m) at least five times. Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers (non-TEAs) are collected for analysis. Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs (Padj < 0.05, |ß| > 0.1) between the two groups. Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L, MAP3K7CL, SEPTI-9, and CUL2. In addition, Gene ontology enrichment analysis reveals several inflammation-related pathways. Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups. In particular, TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count, platelet count, and heart rate. For DNA methylation association analysis, we find that two CpGs (cg16687447, cg06947206) upstream of PTEN were associated with platelet count. In conclusion, extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA, providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.

[Analysis of the 4th generation Scutellaria baicalensis Georgi with space mutagenesis via FTIR spectroscopy].

Determination and analysis for the Scutellaria baicalensis Georgi with space mutagenesis and the ground group were carried out with FTIR for the first time in order to fully understand the quality changes of the 4th generation of space mutagenesis of Scutellaria baicalensis Georgi and do further research. The result shows that for the FTIR spectra of the two samples the position and shape of main absorption peaks are approximately the same, indicating that the major components and the structures of space group remain intact, but the intensities of the absorption peaks are obviously different, with the intensities of the space group significantly enhanced compared to the ground group, especially for the flavonoid compounds (baicalin, baicalein, wogonoside, wogonin and wogonoside etc), which are the main active components of the Scutellaria baicalensis Georgi, the absorption peak intensities at 3391, 1655 and 1069 cm(-1) are obviously stronger than those of the ground group, so the contents of flavonoid compounds and other components are higher, and the amorphous active components are optimized. Space mutation breeding is conducive to breeding new varieties of highly active components, and it is also one of the ways to innovate Chinese medicines germplasm resources efficiently.

Evaluation of the economic impact of brucellosis in domestic yaks of Tibet.

Brucellosis is considered as an endemic disease in yaks (Bos grunniens) in China, but few economic analyses describing the cost of the disease and potential benefits of control have been reported. The aim of the study was to estimate the economic cost of brucellosis in yaks and the economic value of three control strategies: (a) vaccination; (b) test-and-slaughter; and (c) a combination of vaccination and test-and-slaughter programs in Damxung and Maizhokunggar counties and Pali township of Yadong county in Tibet. Using data from a cross-sectional seroprevalence survey conducted in 2015, combined with financial data, the predicted costs and benefits of the different control strategies were simulated over a 6-year period. The annual estimated cost of brucellosis in yaks within the study area was US$ 521,043 (95% CI: US$ 334,441; US$ 759,862), with an annual average cost per yak estimated at US$ 1.42 (95% CI: US$ 0.91, US$ 2.07). The benefit-cost analysis predicted that vaccination was the most effective control method with a benefit-cost ratio (BCR) of 3.19 (95% CI: 2.17, 4.66) and a net present value (NPV) of US$ 313,355 (95% CI: US$ 157,679, US$ 541,062) over a 6-year period. A sensitivity analysis found the NPV was most sensitive to the loss from a female yak aborting in the vaccination control program. In contrast, the price of yaks that were slaughtered had the largest influence on the NPV for both the test-and-slaughter control program and the combination control program. These estimates provide valuable information and establish a foundation for formulating and implementing cost-effective measures for controlling the disease in yaks on the Tibetan plateau, and more broadly in China.

[Research on the fourth generation of Saposhnikovia divaricata by XRF].

To cultivate oriented new varieties, Saposhnikovia divaricata seeds were carried by Shenzhou "3" satellite and filtered when they were being brought back. In the present paper, X-ray fluorescence(XRF) was used to mensurate and analyze the contents of elements of the two samples from the ground group and the 4th generation of space Saposhnikovia divaricata (space group) that have advantages in branches and leaves and yields. The contents of the main mineral elements in the two samples are the same basically. But the contents of the elements Zn, Fe, Mn and Cu from the outer group are higher than the ground group. Especially the contents of Zn, Fe, Mn and Cu concerning the curative effect in the space group increase 4.39, 1.23, 0.84 and 0.9 times as compared to the ground group. In the space group the contents and proportions of the mineral elements are improved and optimized. XRF method can be used for overall element analysis of and research on Chinese herbal medicines. Space flight breeding is an effective method for the selection of new Saposhnikovia divaricata breed.

[Study on spaceflight mutagenesis Platycodon grandiflorum via FTIR].

OBJECTIVE: To establish a method for analyzing amorphous organic compound components of space Platycodon grandflorum rapidly. METHOD: FTIR was applied for measuring and comparing P. grandflorum of comparison group,the ground group and the 4" generation of space group. RESULT: Several active components (platycodin, polysaccharide etc.) contents of space group are increased obviously. CONCLUSION: The major components and the structures remained inextenso,and the effictive component contents are enhanced in the space P. grandiflorum. FTIR is a fast method to analyze the changes of amorphous organic compound components of the space traditional Chinese medicines.

A highly significant association between Cathepsin S gene polymorphisms rs12068264 and chronic obstructive pulmonary disease susceptibility in Han Chinese population.

Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive. In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population. The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique. Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008-1.811, P=0.044) compared with C allele. Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06-4.989, P=0.035). Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels. Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls. In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD.

Association between TAP2 and SEC14L2 polymorphisms and pulmonary tuberculosis risk in the Tibetan Chinese population.

AIM: Pulmonary tuberculosis (PTB) is an infectious disease with a high incidence worldwide. Previous genome-wide association studies have identified multiple susceptibility loci for pulmonary tuberculosis (PTB); however, validation of these findings is still needed. METHODS: For this study, we recruited 300 subjects with PTB and 300 healthy subjects from a Tibetan population living in near or in Xi'an, China. Association analyses of single-nucleotide polymorphisms (SNPs) in TAP2 and SEC14L2 were performed with SPSS Statistics (version 17.0), SNPStats, Haploview (version 4.2), and SHEsis software. RESULTS: We found a correction between one SNP (rs1061660) and PTB based on Chi-square or Fisher's exact tests. In the allelic model analysis, the SNPs rs1061660 in SEC14L2 gene increased PTB 1.32-fold risk (OR = 1.32, CI = 1.05-1.66, P = 0.017). In the genetic model analysis, the rs3819721 in TAP2 gene was associated with increased 1.65-fold risk in the co-dominant model and 1.67-fold risk in the over-dominant model, respectively. For the rs1061660 in SEC14L2 gene, we found it was associated with a 1.49-fold increase the risk of PTB in the dominant model and a 1.37-fold increase the risk of PTB in the log-additive model, respectively. CONCLUSION: We found that two SNPs are associated with increased PTB risk in the Chinese Tibetan population.

MiR-5100 targets TOB2 to drive epithelial-mesenchymal transition associated with activating smad2/3 in lung epithelial cells.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease and the pathogenesis of IPF remains unclear. Our previous study indicated that miR-5100 promotes the proliferation and metastasis of lung epithelial cells. In this study, we investigated the effect and mechanism of miR-5100 on bleomycin (BLM)-induced mouse lung fibrosis and transforming growth factor ß (TGF-ß1) or epidermal growth factor (EGF) induced EMT-model in A549 and Beas-2B cells. The elevated level of miR-5100 was observed in both the mouse lung fibrosis tissues and EMT cell model. Furthermore, the exogenous expression of miR-5100 promoted the EMT-related changes, enhanced TGF-ß1 or EGF-induced EMT and activated the smad2/3 in lung epithelial cells, while silencing miR-5100 had the converse effects. In addition, transwell assay showed that miR-5100 can enhance cell migration. Using target prediction software and luciferase reporter assays, we identified TOB2 as a specific target of miR-5100 and miR-5100 can decrease the accumulation of endogenous TOB2 in A549 and Beas-2B cells. Moreover, the exogenous expression of TOB2 relieves the promotion of miR-5100 on EMT process and migration ability. Taken together, our results indicate that miR-5100 promotes the EMT process by targeting TOB2 associated with activating smad2/3 in lung epithlium cells. Our findings may provide novel insights into the pathogenesis of IPF.