Biomass fuels related-PM2.5 promotes lung fibroblast-myofibroblast transition through PI3K/AKT/TRPC1 pathway.

Emerging evidence has suggested that exposure to PM2.5 is a significant contributing factor to the development of chronic obstructive pulmonary disease (COPD). However, the underlying biological effects and mechanisms of PM2.5 in COPD pathology remain elusive. In this study, we aimed to investigate the implication and regulatory effect of biomass fuels related-PM2.5 (BRPM2.5) concerning the pathological process of fibroblast-to-myofibroblast transition (FMT) in the context of COPD. In vivo experimentation revealed that exposure to biofuel smoke was associated with airway inflammation in rats. After 4 weeks of exposure, there was inflammation in the small airways, but no significant structural changes in the airway walls. However, after 24 weeks, airway remodeling occurred due to increased collagen deposition, myofibroblast proliferation, and tracheal wall thickness. In vitro, cellular immunofluorescence results showed that with stimulation of BRPM2.5 for 72 h, the cell morphology of fibroblasts changed significantly, most of the cells changed from spindle-shaped to star-shaped irregular, α-SMA stress fibers appeared in the cytoplasm and the synthesis of type I collagen increased. The collagen gel contraction experiment showed that the contractility of fibroblasts was enhanced. The expression level of TRPC1 in fibroblasts was increased. Specific siRNA-TRPC1 blocked BRPM2.5-induced FMT and reduced cell contractility. Additionally, specific siRNA-TRPC1 resulted in a decrease in the augment of intracellular Ca2+ concentration ([Ca2+]i) induced by BRPM2.5. Notably, it was found that the PI3K inhibitor, LY294002, inhibited enhancement of AKT phosphorylation level, FMT occurrence, and elevation of TRPC1 protein expression induced by BRPM2.5. The findings indicated that BRPM2.5 is capable of inducing the FMT, with the possibility of mediation by PI3K/AKT/TRPC1. These results hold potential implications for the understanding of the molecular mechanisms involved in BRPM2.5-induced COPD and may aid in the development of novel therapeutic strategies for pathological conditions characterized by fibrosis.

Pregnant women: psychology, cognitive and behavioral responses, and solutions towards COVID-19.

COVID-19 (Corona Virus Disease 2019) has spread globally and is highly infectious, causing psychological disturbances such as anxiety, depression, or both. Pregnant women, as a vulnerable population, need further attention. This study aims to evaluate the psychological impact of pregnant women during COVID-19 to constitute base data for solution guidance. Using a self-designed questionnaire, self-rated anxiety scale (SAS), and self-rated depression scale (SDS), we conducted a web-based survey on 1160 pregnant women from February 20 to April 30, 2020. The prevalence of anxiety and depression during pregnancy was shown to be 12.93% and 31.21%, respectively. Besides, younger age, housewives, lower education level, and early pregnancy all contributed to psychological disturbance during the COVID-19 pandemic. The results revealed significant variations in cognitive and behavioral responses based on the levels of the COVID-19 pandemic concerns, perceptions of life impacts and family concerns, preparation of personal protection equipment and motherhood, and the need for psychological counseling (P < 0.05). Regarding their primary concerns, 73.2% of the participants worried about the health and safety of childbirth. And 90.6% of respondents anticipated scheduling prenatal appointments to avoid crowds. Pregnant women are susceptible to anxiety/depression during the COVID-19 outbreak, necessitating immediate psychological care and intervention.

Contrast-enhanced ultrasonography of the placental barrier; the protective umbrella of the fetus during pregnancy.

AIMS: Ultrasonography is the preferred technique to evaluate the status of maternal and fetal health during pregnancy. Non-obstetric acute or chronic conditions occurring during pregnancy must be diagnosed as early as possible to permit timely and necessary treatment for the sake of maternal and fetal health. The purpose of this study was to evaluate the safety and value of contrast-enhanced ultrasonography (CEUS) during pregnancy. MATERIALS AND METHODS: This prospective study included 14 pregnant women requiring pregnancy termination and six healthy pregnant women. The 14 pregnant women requiring pregnancy termination underwent CEUS prior to surgery to investigate the pattern of contrast agent diffusion. The six healthy pregnant women did not undergo CEUS. The structure of placentae with and without contrast agent injection were also compared by light microscopy. RESULTS: CEUS analysis failed to identify any signs of contrast agents in the umbilical cord blood and fetus. There were no obvious changes in the morphology of placentae with and without contrast agent injection under light microscope. CEUS identified the need for early treatment in one pregnant woman with an ovarian tumor. CONCLUSIONS: Due to the protective effect of the placental barrier on the fetus, CEUS during pregnancy may represent a safe form of imaging technology that can provide valuable information for the diagnosis of non-obstetric acute or chronic disorders and to guide thefuture treatment of pregnant women.

GATA3/long noncoding RNA MHC-R regulates the immune activity of dendritic cells in chronic obstructive pulmonary disease induced by air pollution particulate matter.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness associated with aberrant inflammatory immune reaction in the lung in response to noxious particles and gases. Our previous epidemiological studies discovered that long-term exposure to air pollution PM was associated with an increase in the incidence of COPD and lung function decline, but the impact of air pollution on the onset of COPD and its pathogenesis remains obscure. In recent years, long noncoding RNAs (lncRNAs) have been documented to have a crucial role in COPD. Our preliminary study found that the expression of lncRNA MHC-R in the lung tissues of rats exposed to air pollution PM was dramatically elevated, and the specific expression was mainly focused on the immune-related MHC I, antigen-presenting, and adaptive immune response. After transcription factor prediction, it was found that GATA3 could be combined with the specific sequence of the lncRNA MHC-R promoter region. Dendritic cells (DCs) are necessary antigen-presenting cells (APCs) with the most potent antigen-presenting function. We proved that GATA3/lncRNA MHC-R might regulate the immune activities of DCs to participate in the pathogenic mechanism of COPD induced by air pollution PM, which opens up a new way for early COPD diagnosis and treatment.

Evaluation of right myocardial performance index of in vitro fertilization fetuses and spontaneous pregnancy fetuses: a cross-sectional study.

BACKGROUND: Whether the in vitro fertilization (IVF) has an effect on the cardiac function of the fetus is very important to evaluate the safety of the technique. The aim of this paper is to establish normal reference range for the fetal right myocardial performance index (RMPI), and compare the reference range between IVF fetuses and spontaneous pregnancy (SP) fetuses by automatic measurement of the RMPI. METHODS: Three hundred seventy-one spontaneous singleton pregnancies (the control group) and 39 singleton pregnancies conceived by IVF (the experimental group) were enrolled into the current study. An automatic measurement system was used to acquire the RMPI. The cardiac function of the two groups was compared by t-test. RESULTS: There was no significant difference in normal reference range of RMPI between IVF fetuses and SP fetuses (RMPI 0.42 ± 0.05 vs 0.43 ± 0.05). No strong correlation was also noted between RMPI with gestational age and heart rate. CONCLUSIONS: Normal reference ranges of RMPI of IVF fetuses and SP fetuses were established, and no significant difference between IVF fetuses and SP fetuses in RMPI was found. Thus, these findings may suggest that IVF has little impact on cardiac function of the fetus.

Value of Crystal Vue technique in detecting the placenta accreta spectrum located in c-section scar area.

AIMS: Excessive placental invasion is a life-threatening obstetric disease. Determining the extent of placental villi invasion prenatally is crucial for formulating a surgical plan for pregnant women. The objective of this study was to explore the diagnostic accuracy of the Crystal Vue technique combined with two-dimensional (2D) ultrasound in detecting the degree of placenta accreta spectrum (PAS) located in the C-section scar area. MATERIALS AND METHODS: Twenty-seven pregnant women with a strong suspicion of PAS underwent 2D ultrasound combined with a Crystal Vue examination. The diagnosis of 2D ultrasound alone and Crystal Vue combined with 2D ultrasound was statistically calculated, respectively. Cohen's kappa (k) was used to measure the consistency between these two ultrasound diagnosis and the postoperative diagnosis. RESULTS: The postoperative diagnosis of 27 pregnant women was as follows: 6 cases of placental accreta, 11 cases of placental increta, 2 cases of placental percreta, 2 cases of placental accrete and placental increta, 2 cases of placental accreta and placental percreta, and 4 cases without PAS. Compared with the postoperative diagnosis, 20 cases (74.07%) were correctly diagnosed by 2D ultrasound alone, 6 cases were misdiagnosed, and one case the diagnosis was incomplete, which were substantially consistent with the postoperative diagnosis (k=0.612, p<0.01). Twenty-six cases (96.30%) were correctly diagnosed by Crystal Vue combined with 2D ultrasound; only one case was incomplete diagnosed which was  almost perfectly consistent with the postoperative diagnosis (k=0.934, p<0.01). CONCLUSIONS: Combining the Crystal Vue technique with 2D ultrasound can improve the diagnostic accuracy of ultrasound for detecting all types of PAS located in C-section scar area.

Correction: TRPC6-dependent Ca2+ signaling mediates airway inflammation in response to oxidative stress via ERK pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

TRPC6-dependent Ca2+ signaling mediates airway inflammation in response to oxidative stress via ERK pathway.

Ozone (O3) plays an extremely important role in airway inflammation by generating reactive oxygen species (ROS) including hydrogen peroxide, then promoting redox actions and causing oxidative stress. Evidences indicate that TRPC6 (canonical transient receptor potential channel 6) is a redox-regulated Ca2+ permeable nonselective cation channel, but its role in the setting of oxidative stress-related airway inflammation remains unknown. Here, we found that both TRPC6-/- mice and mice pretreated with SAR7334, a potent TRPC6 inhibitor, were protected from O3-induced airway inflammatory responses. In vitro, both knockdown of TRPC6 expression with shRNA and TRPC6 blockage markedly attenuated the release of cytokines IL-6 and IL-8 induced by O3 or H2O2 in 16HBE cells (human bronchial epithelial cell line). Treatment with O3 or H2O2 enhanced TRPC6 protein expression in vivo and vitro. We also observed that TRPC6-dependent increase of intracellular Ca2+ concentration ([Ca2+]i) was triggered by H2O2, which consisted of the release from intracellular calcium store and the influx of extracellular Ca2+ and could be further strengthened by 6-h O3 exposure in both 16HBE cells and HBEpiCs (primary human bronchial epithelial cells). Moreover, we confirmed that the activation of MAPK signals (ERK1/2, p38, JNK) was required for the inflammatory response induced by O3 or H2O2 while only the phosphorylation of ERK pathway was diminished in the TRPC6-knockdown situation. These results demonstrate that oxidative stress regulates TRPC6-mediated Ca2+ cascade, which leads to the activation of ERK pathway and inflammation and could become a potential target to treat oxidative stress-associated airway inflammatory diseases.

Combined Real-Time Three-Dimensional Hysterosalpingo-Contrast Sonography with B Mode Hysterosalpingo-Contrast Sonography in the Evaluation of Fallopian Tube Patency in Patients Undergoing Infertility Investigations.

OBJECTIVE: This prospective study aimed to investigate the use of real-time three-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy), using contrast agent SonoVue, with B mode hysterosalpingo-contrast sonography (B mode-HyCoSy), to evaluate tubal patency and the wall of the Fallopian tubes in infertility patients. METHOD: In total, we recruited 739 women with fertility requirements from the First Affiliated Hospital of Shantou Medical College between January 2017 and July 2018. All cases received 4D-HyCoSy using contrast agent SonoVue, immediately followed by the B mode-HyCoSy. Of these patients, 145 showed pathological findings in the Fallopian tubes during HyCoSy; 34 of these (62 Fallopian tubes) were verified by laparoscopy and the dye test against routine reference standards. Sonographic findings, along with laparoscopic findings and dye test results, were used to compare the two techniques using the Cohen kappa coefficient. We also investigated the duration of examination and pain score. RESULTS: Compared with laparoscopy and the dye test, the tubal occlusion diagnostic accordance rates for 4D-HyCoSy were 88.7% (32+23)/62, with a kappa coefficient of 0.769 and a 76.9% agreement rate. Distal occlusion diagnostic accordance rates for 4D-HyCoSy were 100% (8/8) with a k coefficient of 1.000 and a 100% agreement rate. CONCLUSIONS: The use of 4D-HyCoSy, with B mode-HyCoSy, for the diagnosis of tubal patency is safe, feasible, noninvasive, and highly accurate. B mode-HyCoSy allowed us to observe tubal walls in an intuitive manner.

TRPC6 modulates adhesion of neutrophils to airway epithelial cells via NF-κB activation and ICAM-1 expression with ozone exposure.

Ozone (O3) is a major component of air pollution, which has been associated with airway inflammation characterized by the influx of neutrophils in asthmatic subjects. Canonical transient receptor potential 6 (TRPC6) channel is recently identified as a target of oxidative stress which is involved in airway inflammation. However, the regulatory role of TRPC6 in airway epithelial cells and neutrophils has not yet been illuminated in detail. In this study, we investigated the role of TRPC6 in neutrophil adhesion to airway epithelial cells exposed to O3 in vivo and in vitro approaches. Using transgenic mice, the results showed that TRPC6-deficiency attenuated O3-induced neutrophil recruitment to airway epithelial cells and intercellular adhesion molecule-1 (ICAM-1) expression. In vitro, O3 induced ICAM-1 expression and neutrophil adhesion to 16HBE cells (human airway epithelial cell line) and which were reduced by both TRPC6 silencing short hairpin RNA (shRNA) and TRPC6 inhibitor Larixyl Acetate (LA). We also confirmed that TRPC6-dependent Ca2+ entry and NF-κB activation in 16HBE cells were required for ICAM-1-mediated neutrophil adhesion exposed to O3. In conclusion, this study demonstrated the contribution of TRPC6 to O3-induced neutrophil adhesion to airway epithelial cells via NF-κB activation and ICAM-1 expression, which may provide new potential concepts for preventing and treating air pollutant-related inflammatory lung diseases.

TRPC6 contributes to LPS-induced inflammation through ERK1/2 and p38 pathways in bronchial epithelial cells.

receptor potential canonical (TRPC) channels are presently an emerging target for airway disorders. Recent evidence has indicated that TRPC6 as a member of the TRPC family plays an important role in airway inflammation, but its precise function in bronchial epithelial cells remains unclear. The aim of this study was to investigate the role of TRPC6 in Toll-like receptor 4 (TLR4)-mediated inflammation in human bronchial epithelial cells stimulated by endotoxin [lipopolysaccharide (LPS)]. Hyp9 is a simplified phloroglucinol derivative of hyperforin that highly selectively activates TRPC6 channels. The results show that the activation of TRPC6 by Hyp9 induced the production of interleukin (IL)-8 and IL-6. LPS was also able to induce the release of IL-8 and IL-6, which was significantly aggravated by Hyp9 and reduced by knockdown of TRPC6. Treatment with LPS not only chronically induced the expression of TRPC6 mRNA and protein in a TLR4-dependent manner but also acutely increased Ca2+ influx through TRPC6 channels. In addition, LPS-induced overexpression of TRPC6 and Ca2+ influx were associated with the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt. Importantly, TRPC6 was required for the activation of ERK1/2, p38, and NF-κB. In conclusion, these data reveal that LPS induced the overexpression of TRPC6 and TRPC6-dependent Ca2+ influx via the TLR4/PI3K/Akt pathway resulting in Ca2+ mobilization, which subsequently promoted the activation of ERK1/2, p38, and NF-κB and the inflammatory response in bronchial epithelial cells.

[N-acetyl-L-cysteine reduces the ozone-induced lung inflammation response in mice].

In this study, we investigated the protective effect of the antioxidant N-acetyl-L-cysteine (NAC) on the lung inflammation caused by ozone (O3) exposure in mice. Thirty-two C57BL/6 mice were randomly divided into control group, O3 group, O3+NAC group and NAC group. Mice were exposed to O3 (1.0 ppm) or fresh air for 3 h on the day 1, day 3 and day 5, respectively. NAC (100 mg/kg) was intraperitoneally applied to the mice 1 h before each exposure. At 24 h after the 3-time exposure, the alveolar wall structure was severely damaged and the infiltrated inflammatory cells were apparent perivascularly and peribronchiolarly. Significant increases in the total white blood cell count, macrophage, lymphocyte and neutrophil counts, as well as total protein concentration were observed in the bronchoalveolar lavage fluid (BALF) (P < 0.05). The IL-6, IL-8 (P < 0.01) and MDA levels (P < 0.05) in the lung homogenates were elevated coherently. Administration of NAC could attenuate the alveolar wall structure damage induced by O3 exposure and reduce the amount of infiltrated inflammatory cells, total and differential leukocyte counts (P < 0.05), as well as the IL-6, IL-8 (P < 0.01) and MDA release (P < 0.05). Western blotting results showed that the O3 exposure up-regulated the p38 MAPK and NF-κB p65 protein expression in the lung tissue of mice (P < 0.05), which could be alleviated by NAC (P < 0.05). These results indicated that NAC could protect against O3-induced pulmonary inflammation in mice. The beneficial effect of NAC might be related with the p38 MAPK and NF-κB p65 signal pathway.