Galectin-3 inhibition ameliorates alveolar epithelial cell pyroptosis in phosgene-induced acute lung injury.

Phosgene is a type of poisonous gas that can cause acute lung injury (ALI) upon accidental exposure. Casualties still occur due to phosgene-induced acute lung injury (P-ALI) from accidents resulting from improper operations. The pathological mechanisms of P-ALI are still understudied. Thus, we performed scRNA-seq on cells isolated from all subpopulations of the BALF in P-ALI and found that Gal3 expression was significantly higher in the gas group than in the control group. Further analysis revealed a ligand-receptor correspondence between alveolar macrophages (AMs) and alveolar epithelial cells (AEC), with Gal3 playing a key role in this interaction. To confirm and elaborate on this discovery, we selected four time points during the previous week: sham (day 0), day 1, day 3, and day 7 in the P-ALI mouse model and found that Gal3 expression was significantly elevated in P-ALI, most abundantly expressed in AM cells. This was further confirmed with the use of a Gal3 inhibitor. The inhibition of Gal3 and elimination of AMs in mice both attenuated epithelial cell pyroptosis, as confirmed in in vitro experiments, and revealed the Gal3/caspase-8/GSDMD signaling pathway. These findings suggest that Galectin-3 inhibition can ameliorate AEC pyroptosis by inhibiting the Gal3/caspase-8/GSDMD signaling pathway, thus reducing alveolar damage in mice with P-ALI. This finding provides novel insights for improving treatment efficacy for P-ALI.

Curcumin suppresses the Wnt/ß-catenin signaling pathway by inhibiting NKD2 methylation to ameliorate intestinal ischemia/reperfusion injury.

Intestinal ischemia/reperfusion (I/R) injury is a life-threatening condition with no effective treatment currently available. Curcumin (CCM), a polyphenol compound in Curcuma Longa, reportedly has positive effects against intestinal I/R injury. However, the mechanism underlying the protective effect of CCM against intestinal I/R injury has not been fully clarified. To determine whether the protective effect of CCM was mediated by epigenetic effects on Wnt/ß-catenin signaling, the effect of CCM was examined in vivo and in vitro. An intestinal I/R model was established in Sprague-Dawley (SD) rats with superior mesenteric artery occlusion, and Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) for in vivo simulation of I/R. The results showed that CCM significantly reduced inflammatory, cell apoptosis, and oxidative stress induced by I/R insult in vivo and in vitro. Western blot analysis showed that CCM preconditioning reduced the protein levels of ß-catenin, p-GSK3ß, and cyclin-D1 and increased the protein level of GSK3ß compared with the I/R group. Overexpressing ß-catenin aggravated H/R injury, and knocking down ß-catenin relieved H/R injury by improving intestinal permeability and reducing the cell apoptosis. Moreover, Naked cuticle homolog 2(NKD2) mRNA and protein levels were upregulated in the CCM-pretreated group. 5-aza-2'-deoxycytidine (5-AZA) treatment improved intestinal epithelial barrier impairment induced by H/R. Besides, the protein levels of total ß-catenin, phosphor-ß-catenin and cyclin-D1 were reduced after overexpressing NKD2 in Caco-2 cells following H/R insult. In conclusion, Our study suggests that CCM could attenuate intestinal I/R injury in vitro and in vivo by suppressing the Wnt/ß-catenin signaling pathway via inhibition of NKD2 methylation.

PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury.

Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA sequencing, and have been shown to attenuate P-ALI by promoting lung vascular barrier repair. As a transcription factor closely related to angiogenesis, whether PTTG1 plays a role in CD34+CD45+ cell repairing the pulmonary vascular barrier in rats with P-ALI remains unclear. This study provided compelling evidence that CD34+CD45+ cells possess endothelial differentiation potential. Rats with P-ALI were intratracheally administered with CD34+CD45+ cells transfected with or without PTTG1-overexpressing and sh-PTTG1 lentivirus. It was found that CD34+CD45+ cells reduced the pulmonary vascular permeability and mitigated the lung inflammation, which could be reversed by knocking down PTTG1. Although PTTG1 overexpression enhanced the ability of CD34+CD45+ cells to attenuate P-ALI, no significant difference was found. PTTG1 was found to regulate the endothelial differentiation of CD34+CD45+ cells. In addition, knocking down of PTTG1 significantly reduced the protein levels of VEGF and bFGF, as well as their receptors, which in turn inhibited the activation of the PI3K/AKT/eNOS signaling pathway in CD34+CD45+ cells. Moreover, LY294002 (PI3K inhibitor) treatment inhibited the endothelial differentiation of CD34+CD45+ cells, while SC79 (AKT activator) yielded the opposite effect. These findings suggest that PTTG1 can promote the endothelial differentiation of CD34+CD45+ cells by activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway, leading to the repair of the pulmonary vascular barrier in rats with P-ALI.

RGD-Hydrogel Improves the Therapeutic Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Phosgene-Induced Acute Lung Injury in Rats.

Mesenchymal stem cells (MSCs) have promising potential in the treatment of various diseases, such as the therapeutic effect of bone marrow-derived MSCs for phosgene-induced acute lung injury (P-ALI). However, MSC-related therapeutics are limited due to poor cell survival, requiring appropriate MSC delivery systems to maximise therapeutic capacity. Biomaterial RGD-hydrogel is a potential cell delivery vehicle as it can mimic the natural extracellular matrix and provide cell adhesion support. The application of RGD-hydrogel in the MSC treatment of respiratory diseases is scarce. This study reports that RGD-hydrogel has good biocompatibility and can increase the secretion of Angiopoietin-1, hepatocyte growth factor, epidermal growth factor, vascular endothelial cell growth factor, and interleukin-10 in vitro MSCs. The hydrogel-encapsulated MSCs could further alleviate P-ALI and show better cell survival in vivo. Overall, RGD-hydrogel could improve the MSC treatment of P-ALI by modulating cell survival and reparative activities. It is exciting to see more and more ways to unlock the therapeutic potential of MSCs.

Risk of anxiety and depression in patients with lichen planus: A nationwide population-based study.

BACKGROUND: This study aims to determine the risk of developing anxiety and/or depression among patients with lichen planus. METHODS: Based on the Longitudinal Health Insurance Database of Taiwan National Health Insurance Research Database, a total of 4012 patients with lichen planus and 16,048 matched controls (1:4) were enrolled between January 1, 2000, and December 31, 2015. After controlling for the risk variables, multivariate Cox proportional hazard regression and the log-rank test with Kaplan-Meier method were performed to assess the influence of anxiety/depression among individuals with lichen planus under a maximum follow-up period of 16 years. RESULTS: The subsequent anxiety or depression incidence of the lichen planus group and the comparisons was 19.67% (1962.70 per 105 person-years) and 10.11% (982.23 per 105person-years), respectively. Additionally, after adjustment of the risk variables, the hazard ratios for anxiety, depression, anxiety without depression, depression without anxiety, anxiety or depression, and both anxiety and depression combined were 1.779 (95%CI: 1.289-2.477, p < 0.001), 2.010 (95%CI: 1.454-2.790, p < 0.001), 2.015 (95%CI: 1.463-2.799, p < 0.001), 2.356 (95%CI: 1.705-3.286, p < 0.001), 2.011 (95%CI: 1.457-2.793, p < 0.001), and 1.515 (95%CI: 1.100-2.134, p < 0.001), respectively. LIMITATIONS: Individuals with lichen planus were unable to be classified into oral subtype and cutaneous subtype based on the ICD-9-CM. Moreover, the results of our study could not demonstrate the mechanism between lichen planus and anxiety and/or depression. CONCLUSION: Patients with lichen planus was positively associated with developing anxiety or depression. Physicians should to be aware of the signs of anxiety and/or depression while facing the patients with lichen planus during the clinical practices.

Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury.

Alveolar epithelial cells (AECs) play a role in chemically induced acute lung injury (CALI). However, the mechanisms that induce alveolar epithelial type 2 cells (AEC2s) to proliferate, exit the cell cycle, and transdifferentiate into alveolar epithelial type 1 cells (AEC1s) are unclear. Here, we investigated the epithelial cell types and states in a phosgene-induced CALI rat model. Single-cell RNA-sequencing of bronchoalveolar lavage fluid (BALF) samples from phosgene-induced CALI rat models (Gas) and normal controls (NC) was performed. From the NC and Gas BALF samples, 37,245 and 29,853 high-quality cells were extracted, respectively. All cell types and states were identified and divided into 23 clusters; three cell types were identified: macrophages, epithelial cells, and macrophage proliferating cells. From NC and Gas samples, 1315 and 1756 epithelial cells were extracted, respectively, and divided into 11 clusters. The number of AEC1s decreased considerably following phosgene inhalation. A unique SOX9-positive AEC2 cell type that expanded considerably in the CALI state was identified. This progenitor cell type may develop into alveolar cells, indicating its stem cell differentiation potential. We present a single-cell genome-scale transcription map that can help uncover disease-associated cytologic signatures for understanding biological changes and regeneration of lung tissues during CALI.

Foliar application of selenium and zinc to alleviate wheat (Triticum aestivum L.) cadmium toxicity and uptake from cadmium-contaminated soil.

Due to the large area of agricultural soils contaminated by Cd worldwide, cost-effective and practical method for safety food production are necessary. The roles of micronutrient on reducing Cd accumulation in crops are recently introduced. In the current study, a pot-culture experiment in the greenhouse was conducted to study the foliar spraying of Se (Na2SeO4) and Zn (ZnSO4) on physiological and growth parameters, as well as Cd concentrations in wheat plants grown in Cd-contaminated soil. The foliar was sprayed with four concentration of Se and Zn (0, 10, 20, and 40 mg L-1) at different growth stage (tillering, elongating and heading) and whole wheat plants were collected after maturity. Both foliar spraying with Se and Zn significantly enhanced the photosynthesis, tissue biomass and antioxidant enzyme activity. Additionally, Se and Zn application can also increase Se and Zn concentrations in different plant tissues. Selenium and Zn decreased malondialdehyde (MDA) and Cd concentrations in wheat grains, hulks, leaves, stalks and root in a dose-additive manner. Overall, Se and Zn both efficiently enhanced the wheat growth and Se and Zn concentrations, and simultaneously decreased the Cd concentration in wheat plant. Compared with Zn, Se more efficiently improved wheat growth and reduced Cd concentration in the wheat in a Cd-contaminated soil. Present results suggest that use of foliar spraying, especially Se, could be a cost-effective strategy and could be recommended for remediation of light-or moderate-polluted soils contaminated by Cd.

[Modeling of Water Quality Response to Land-use Patterns in Taizi River Basin Based on Partial Least Squares].

Land use change in river basin is one of the most significant factors that influence river water quality. Based on remote sensing images and river water quality data of Taizi River Basin, partial least squares (PLS) model was applied to explore the relationship between water quality and land use patterns at sub-watershed scale. In this study, PLS model was established by using the percentage of area of land use patterns from seven different sub-watersheds as the variables and the concentrations of four water quality parameters as the observations. The established model was further tested with the data from other sub-watersheds in Taizi River Basin. The results indicated that total nitrogen (TN) and nitrate (NO3-) were significantly associated with land use types in Taizi River Basin with determination coefficient (R2) greater than 0.62. As for chloride (Cl-) and sulfate (SO42-), measured values and fitted values had a relatively low fitting precision (R2<0.5), which meant land use pattern was not the main factor affecting the concentrations of Cl-and SO42- in river water. Meanwhile, river water quality had a strong correlation with the percentage of area of unused land at the sub-basin scale (influence coefficient>0.24), although unused land area in the Taizi river basin was small.

Effect of traditional Chinese herbs combined with low dose human menopausal gonadotropin applied in frozen-thawed embryo transfer.

OBJECTIVE: To assess embryo implantation rate (IR) and pregnancy rate (PR) in women who received Bushen Wengong Decoction (BSWGD), a Chinese herbal formula, combined with low dose of human menopausal gonadotropin (hMG) prior to frozen-thawed embryo transfer (FET). METHODS: A total of 262 subjects (674 transferred embryos) who received FET were analyzed retrospectively. In them, 122 women were under 30 years old, 106 between 30 - 35 years and 32 over 35 years. The 85 subjects with normal ovulation were assigned to Group A, the natural menstruation cycling group, on whom no pre-transfer treatment was applied. The other 177 subjects with abnormal ovulation were assigned to Group B, and subdivided, according to the pre-transfer treatment they received, into three groups, Group B1 (50 cases) received BSWGD, Group B2 (58 cases) received hMG and Group B3 (69 cases) received both BSWGD and low dose hMG. The IR and PR of FET in the four groups were compared, and the effect of the embryo cryotime on PR of FET were compared also. Besides, the influencing factors to FET were analyzed. RESULTS: IR and PR were significantly higher in all age sects of Group B3 than those in Group A, showing significant difference (P< 0.05). IR and PR in subjects in age sects of <30 years and > 35 years in group B3 were significantly higher than those in Group B1 ( P<0.05), but no significant difference was shown in the two parameters between Group B 2 and Group B3 (P>0.05). PR in the subjects who received embryos with cryo-time of > 200 days was significantly lower than that in those with cryo-time of < 100 days ( P<0.05). Embryo cryo-time, endometrial thickness, use of BSWGD and use of hMG were of significance in FET ( P 0.05). CONCLUSION: A programmed cycle of BSWGD combined with low dose of hMG could improve the embryo IR and PR of FET. Embryo cryo-time, endometrial thickness, and the use of BSWGD and hMG are of significance for FET.