Continual Exposure to Cigarette Smoke Extracts Induces Tumor-Like Transformation of Human Nontumor Bronchial Epithelial Cells in a Microfluidic Chip

IntroductionHeavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear.MethodsIn our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE.ResultsOur results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways.ConclusionsThe established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling

A calcineurin–Hoxb13 axis regulates growth mode of mammalian cardiomyocytes

10.1038/s41586-020-2228-6Nature5827811271-27

Transcription analysis on response of swine lung to H1N1 swine influenza virus

<p>Abstract</p> <p>Background</p> <p>As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs.</p> <p>Results</p> <p>At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes.</p> <p>Conclusions</p> <p>This study shows how the target organ responds to H1N1 swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.</p

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

The association between inter-twin birth weight discordance and hepatitis C: The United States 2011-2015 twin birth registration data.

BACKGROUND:Twins with discordant growth have increased risks of perinatal mortality and morbidity. Previous studies have identified a number of risk factors for inter-twin birth weight discordance, yet no study has examined the effect of maternal hepatitis C infection. METHODS:We used the twin birth records extracted from the 2011 to 2015 United States birth records created by the Centers for Disease Control and Prevention. The outcome variable of this study was inter-twin birth weight discordance, defined as [(birth weight of larger twin-birth weight of smaller twin) / birth weight of larger twin]. The independent association of hepatitis C infection with birth weight discordance was examined using the gamma regression or log binomial regression, adjusted by potential confounders. RESULTS:Of the 270,256 twin pairs included in the final analysis, 850 (0.31%) had positive hepatitis C. Compared to mothers without hepatitis C, mothers with hepatitis C positive tended to have higher risk of birth weight discordance, but with no statistical significance. After adjustment for potential confounding factors, hepatitis C positive became a significant risk factor for birth weight discordance >25% (relative risk 1.14, 95% confidence interval 1.02-1.29). Sensitivity analyses (by treating birth weight discordance as a continuous outcome or dichotomizing into by different cutoffs) yielded similar results, with relative risks ranging from 1.07 to 1.12 (all P<0.05). CONCLUSION:Maternal hepatitis C positive is associated with inter-twin birth weight discordance, an important adverse infant outcome in twin pregnancies, although the effect size is small

NRG1 knockdown rescues PV interneuron GABAergic maturation deficits and schizophrenia behaviors in fetal growth restriction mice

Abstract Schizophrenia is a highly debilitating mental disorder, those who experienced fetal growth restriction (FGR) in the early stage of life have a greater probability of schizophrenia. In this study, FGR mice showed hyperactivity in locomotor activity test, sociability dysfunction in three chamber test and nesting social behavior tests, cognition decline in Morris water maze and impaired sensory motor gating function in prepulse inhibition test. Mechanistic studies indicated that the number of parvalbumin (PV) interneuron was significantly reduced in FGR mouse media prefrontal cortex (mPFC). And the mRNA and protein level of neuregulin 1(NRG1), which is a critical schizophrenia gene, increased significantly in FGR mouse mPFC. Furthermore, NRG1 knockdown in FGR mouse mPFC improved PV interneuron GABAergic maturation and rescued schizophrenia behaviors including hyperactivity, social novelty defects, cognition decline, and sensorimotor gating deficits in FGR mice. This study indicates that mPFC NRG1 upregulation is one of the main causes of FGR-induced schizophrenia, which leads to significant reduction of PV interneuron number in mPFC. NRG1 knockdown in mPFC significantly rescues schizophrenia behaviors in FGR mouse. This study thus provides a potential effective therapy target or strategy for schizophrenia patients induced by FGR

Previous antibiotic treatment as a risk factor for recurrent vulvovaginal candidiasis

The incidence of recurrent vulvovaginal candidiasis (RVVC) is extremely high. RVVC is likely to have a greater impact on patients. The aim of the study was to explore the risk factors of recurrent vulvovaginal candidiasis (RVVC) in the tropical coastal area. In this case-control study, a questionnaire survey was conducted in patients with VVC in the Sanya area from July 2014 to December 2016. The data included demographic characteristics, host factors, and behavioural characteristics. According to the maximum number of symptomatic episodes per year, the participants were classified into a non-recurrent VVC (NRVVC; &lt; 4 episodes/year, including the current one) group or a RVVC group (&ge; 4 episodes/year, including the current one). Crude odds ratios were calculated for potential risk factors and were adjusted using logistic regression. All vaginal secretions of patients with RVVC were cultured. Of the 728 cases of VVC, 69.0% (502/728) were NRVVC, and 31.0% (226/728) were RVVC. Previous antibiotic treatment (adjusted OR: 4.41, p &lt; 0.01), repeat abortion (p &lt; 0.05), and vaginal lavage (adjusted OR: 1.62, p &lt; 0.05) were significantly associated with RVVC. A total of 230 yeasts isolates were obtained from 226 patients. C. albicans were the predominant Candida species (194 strains) in all patients of VVC. Our results demonstrate that in the tropical coastal area, a significant association was found between previous antibiotic treatment and incident RVVC. Host factors may be the most important factors in the occurrence of RVVC

Associations between velamentous or marginal cord insertion and risk of adverse perinatal outcomes in twin pregnancies: a retrospective cohort study

Abstract Background Velamentous cord insertion (VCI) and marginal cord insertion (MCI) are well-known risk factors for adverse perinatal outcomes in singleton pregnancies. However, the potential links between VCI or MCI and perinatal outcomes in twin pregnancies have yet to be systematically evaluated. This study aimed to investigate the relationships between VCI or MCI and perinatal outcomes in twin pregnancies. Methods This retrospective single-center cohort study included women with twin pregnancies who gave birth in a tertiary hospital in Southwest, China between January 2017 and December 2022. VCI and MCI were identified by abdominal ultrasound and confirmed after placental delivery. Logistic regression, multinomial logit regression and generalized estimation equation models were used to evaluate the association between VCI or MCI and perinatal outcomes. Results A total of 3682 twin pregnancies were included, including 100 (2.7%) pregnancies with VCI and 149 (4.0%) pregnancies with MCI. Compared to pregnancies with normal cord insertion, both monochorionic and dichorionic pregnancies with VCI were associated with an increased risk of preterm delivery 32–34 weeks (aRRR 2.94, 95% CI 1.03–8.39; aRRR 2.55, 95% CI 1.19–5.46, respectively), while pregnancies with MCI were not associated with preterm delivery. VCI was associated with a higher incidence of placental previa (aOR 6.36, 95% CI 1.92–21.04) in monochorionic pregnancies and placental accreta (aOR 1.85, 95% CI 1.06–3.23) in dichorionic pregnancies. MCI was associated with an increased risk of preeclampsia (aOR 3.07, 95% CI 1.49–6.32), intertwin birthweight discordance ≥ 20% (aOR 2.40, 95% CI 1.08–5.60) and selective fetal growth restriction (aOR 2.46, 95% CI 1.08–5.60) in monochorionic pregnancies and small-for-gestational age neonates (aOR 1.97, 95% CI 1.24–3.14) in dichorionic pregnancies. Conclusions VCI was associated with an increased risk of preterm delivery in twin pregnancies irrespective of chorionicity, whereas MCI was associated with an increased preeclampsia risk, significant intertwin birthweight discordance in monochorionic pregnancies and small-for-gestational age neonates in dichorionic pregnancies

High and low dose of luzindole or 4-phenyl-2-propionamidotetralin (4-P-PDOT) reverse bovine granulosa cell response to melatonin

Background Communication between oocytes and granulosa cells ultimately dictate follicle development or atresia. Melatonin is also involved in follicle development. This study aimed to investigate the effects of melatonin and its receptor antagonists on hormone secretion, as well as gene expression related to hormone synthesis, TGF-β superfamily, and follicle development in bovine granulosa cells, and assess the effects of melatonin in the presence of 4-P-PDOT and luzindole. Methods Bovine ovaries were collected from a local abattoir and follicular fluid (follicle diameter 5–8 mm) was collected for granulosa cell isolation and culture. Granulosa cells and culture medium were collected 48 h after treatment with melatonin at high dose concentrations (10−5 M) and low dose concentrations (10−9 M) in the absence/presence of 4-P-PDOT and luzindole (10−5 M or 10−9 M). Furthermore, the expression level of genes related to hormonal synthesis (CYP11A1, CYP19A1, StAR, and RUNX2), TGF-β superfamily (BMP6, INHA, INHBA, INHBB, and TGFBR3), and development (EGFR, DNMT1A, and FSHR) were detected in each experimental group by real-time quantitative PCR. In addition, the level of hormones in culture medium were detected using ELISA. Results Both 10−5 M and 10−9 M melatonin doses promoted the secretion of inhibin A and progesterone without affecting the production of inhibin B and estradiol. In addition, both promoted the gene expression of INHA, StAR, RUNX2, TGFBR3, EGFR, and DNMT1A, and inhibited the expression of BMP6, INHBB, CYP11A1, CYP19A1, and FSHR. When combined with different doses of 4-P-PDOT and luzindole, they exhibited different effects on the secretion of inhibin B, estradiol, inhibin A, and progesterone, and the expression of CYP19A1, RUNX2, BMP6, INHBB, EGFR, and DNMT1A induced by melatonin. Conclusion High and low dose melatonin receptor antagonists exhibited different effects in regulating hormone secretion and the expression of various genes in response to melatonin. Therefore, concentration effects must be considered when using luzindole or 4-P-PDOT

Imaging and quantification of iron-oxide nanoparticles (IONP) using MP-RAGE and UTE based sequences.

PurposeTo investigate two-dimensional (2D) and three-dimensional (3D) ultrashort echo time (UTE) and 3D magnetization-prepared rapid gradient-echo (MP-RAGE) sequences for the imaging of iron-oxide nanoparticles (IONP).MethodsThe phantoms were composed of tubes filled with different IONP concentrations ranging from 2 to 45 mM. The tubes were fixed in an agarose gel phantom (0.9% by weight). Morphological imaging was performed with 3D MP-RAGE, 2D UTE, 2D adiabatic inversion recovery-prepared UTE (2D IR-UTE), 3D UTE with Cones trajectory (3D Cones), and 3D IR-Cones sequences. Quantitative assessment of IONP concentration was performed using R2*(1/T2*) and R1 (1/T1 ) measurements using a 3 Tesla (T) scanner.ResultsThe 3D MP-RAGE sequence provides high-contrast images of IONP with concentration up to 7.5 mM. Higher IONP concentration up to 37.5 mM can be detected with the UTE sequences, with the highest IONP contrast provided by the 3D IR-Cones sequence. A linear relationship was observed between R2* and IONP concentration up to ∼45 mM, and between R1 and IONP concentration up to ∼30 mM.ConclusionThe clinical 3D MP-RAGE sequence can be used to assess lower IONP concentration up to 7.5 mM. The UTE sequences can be used to assess higher IONP concentration up to 45 mM. Magn Reson Med 78:226-232, 2017. © 2016 International Society for Magnetic Resonance in Medicine