Effect of microplastics on nasal and intestinal microbiota of the high-exposure population.

Background: Microplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational cross-sectional study focusing on the effects of microplastics on the nasal and gut microbiota in a highly exposed population. Methods: We recruited 20 subjects from a Plastic Factory (microplastics high-exposure area) and the other 20 from Huanhuaxi Park (microplastics low-exposure area) in Chengdu, China. We performed the microplastic analysis of soil, air, and intestinal secretions by laser infrared imaging, and microbiological analysis of nasal and intestinal secretions by 16S rDNA sequencing. Results: The result shows that the detected points of microplastics in the environment of the high-exposure area were significantly more than in the low-exposure area. Polyurethane was the main microplastic component detected. The microplastic content of intestinal secretions in the high-exposure group was significantly higher than in the low-exposure group. Specifically, the contents of polyurethane, silicone resin, ethylene-vinyl acetate copolymer, and polyethylene in the high-exposure group were significantly higher than in the low-exposure group. Moreover, high exposure may increase the abundance of nasal microbiotas, which are positively associated with respiratory tract diseases, such as Klebsiella and Helicobacter, and reduce the abundance of those beneficial ones, such as Bacteroides. Simultaneously, it may increase the abundance of intestinal microbiotas, which are positively associated with digestive tract diseases, such as Bifidobacterium, Streptococcus, and Sphingomonas, and reduce the abundance of intestinal microbiotas, which are beneficial for health, such as Ruminococcus Torquesgroup, Dorea, Fusobacterium, and Coprococcus. A combined analysis revealed that high exposure to microplastics may not only lead to alterations in dominant intestinal and nasal microbiotas but also change the symbiotic relationship between intestinal and nasal microbiotas. Conclusion: The results innovatively revealed how microplastics can affect the intestinal and nasal microecosystems. Clinical trial registration: ChiCTR2100049480 on August 2, 2021.

Cdc42 upregulation under high glucose induces podocyte apoptosis and impairs ß-cell insulin secretion.

Objectives: The progressive impairment of ß-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet ß-cells. Methods: Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and ß-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in ß-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells. Results: Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of ß-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of ß-TC6 cells. The expression of Cdc42 and p-p38 in ß-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells. Conclusions: Cdc42 in podocytes plays a crucial role in insulin secretion by ß-cells, which may provide a new therapeutic target to prevent the vicious cycle of ß-cell dysfunction in T2DM.

Emodin Alleviates High-Glucose-Induced Pancreatic ß-Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling.

Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic ß-cell (ß-cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the ß-cells in DM remains unclear, and therapeutic approaches to it are limited. Emodin (EMD), a natural anthraquinone derivative, has been preliminarily proven to show antidiabetic effects. However, the underlying mechanism of EMD on ß-cells still needs to be elucidated. In this study, we investigated the protective effects of EMD on the high glucose (50 mM)-induced INS-1 cell line and the underlying mechanism. INS-1 cells were treated with EMD (5, 10, and 20 µM) when exposed to high glucose. The effects of EMD were examined by using the inverted phase-contrast microscope, qRT-PCR, ELISA, and western blot. The results showed that EMD could alleviate cellular morphological changes, suppress IL-1ß and LDH release, and promote insulin secretion in high-glucose-induced INS-1 cells. Furthermore, EMD inhibits NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage to alleviate pyroptosis induced by high glucose. Overexpression of NLRP3 reversed the above changes caused by EMD. Collectively, our findings suggest that EMD attenuates high-glucose-induced ß-cell pyroptosis by inhibiting NLRP3/GSDMD signaling.

Integrated analysis identifies DUSP5 as a novel prognostic indicator for thyroid follicular carcinoma.

BACKGROUND: Differentiated thyroid cancer involves thyroid follicular carcinoma (FTC) and papillary thyroid carcinoma (PTC). Patients with FTC have a worse prognosis than those with PTC for early metastasis through blood of FTC. However, the mechanism of poor prognosis of FTC is still unclear. Here, we aim to evaluate the role of DUSP5 in the prognostic evaluation of FTC. METHOD: We searched the Gene Expression Omnibus (GEO) database for the differentially expressed genes (DEGs) between FTC and PTC, and then combined with survival analysis of cBioPortal database to locate the gene significantly related to prognosis. Tissue microarrays and clinical tissues were used to examine DUSP5 expression by immunohistochemical (IHC) staining between FTC and PTC tissues. In vitro experiment, proliferation, migration and invasion of FTC were observed after regulation of DUSP5 by transfection of siRNA and plasmids, respectively. RESULTS: After searching the GEO database, 26 DEGs were found. DUSP5 was significantly associated with prognosis of FTC in combination with survival analysis. Data of IHC staining showed lower expression of DUSP5 in FTC compared to PTC tissues. Furthermore, overexpression of DUSP5 inhibited the proliferation, migration and invasion accompanied with low level of MMP9 and Vimentin and high level of E-cadherin. Nevertheless, inhibition of DUSP5 ameliorated above damaging effect on the proliferation, migration and invasion. CONCLUSION: DUSP5 was differentially expressed in FTC and PTC tissues. Low level of DUSP5 in FTC participates in the high frequency of metastasis, and further contributes to poor prognosis of FTC. DUSP5 could be served as a novel therapeutic target for FTC.