Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.

BACKGROUND: Hypoxia is a major cause and promoter of pulmonary hypertension (PH), a representative vascular remodeling disease with poor prognosis and high mortality. However, the mechanism underlying how pulmonary arterial system responds to hypoxic stress during PH remains unclear. Endothelial mitochondria are considered signaling organelles on oxygen tension. Results from previous clinical research and our studies suggested a potential role of posttranslational SUMOylation (small ubiquitin-like modifier modification) in endothelial mitochondria in hypoxia-related vasculopathy. METHODS: Chronic hypoxia mouse model and Sugen/hypoxia rat model were employed as PH animal models. Mitochondrial morphology and subcellular structure were determined by transmission electron and immunofluorescent microscopies. Mitochondrial metabolism was determined by mitochondrial oxygen consumption rate and extracellular acidification rate. SUMOylation and protein interaction were determined by immunoprecipitation. RESULTS: The involvement of SENP1 (sentrin-specific protease 1)-mediated SUMOylation in mitochondrial remodeling in the pulmonary endothelium was identified in clinical specimens of hypoxia-related PH and was verified in human pulmonary artery endothelial cells under hypoxia. Further analyses in clinical specimens, hypoxic rat and mouse PH models, and human pulmonary artery endothelial cells and human embryonic stem cell-derived endothelial cells revealed that short-term hypoxia-induced SENP1 translocation to endothelial mitochondria to regulate deSUMOylation (the reversible process of SUMOylation) of mitochondrial fission protein FIS1 (mitochondrial fission 1), which facilitated FIS1 assembling with fusion protein MFN2 (mitofusin 2) and mitochondrial gatekeeper VDAC1 (voltage-dependent anion channel 1), and the membrane tethering activity of MFN2 by enhancing its oligomerization. Consequently, FIS1 deSUMOylation maintained the mitochondrial integrity and endoplasmic reticulum-mitochondria calcium communication across mitochondrial-associated membranes, subsequently preserving pulmonary endothelial function and vascular homeostasis. In contrast, prolonged hypoxia disabled the FIS1 deSUMOylation by diminishing the availability of SENP1 in mitochondria via inducing miR (micro RNA)-138 and consequently resulted in mitochondrial dysfunction and metabolic reprogramming in pulmonary endothelium. Functionally, introduction of viral-packaged deSUMOylated FIS1 within pulmonary endothelium in mice improved pulmonary endothelial dysfunction and hypoxic PH development, while knock-in of SUMO (small ubiquitin-like modifier)-conjugated FIS1 in mice exaggerated the diseased cellular and tissue phenotypes. CONCLUSIONS: By maintaining endothelial mitochondrial homeostasis, deSUMOylation of FIS1 adaptively preserves pulmonary endothelial function against hypoxic stress and consequently protects against PH. The FIS1 deSUMOylation-SUMOylation transition in pulmonary endothelium is an intrinsic pathogenesis of hypoxic PH.

Perceptions of Chinese older adults with type 2 diabetes mellitus about self-management mobile platform: A qualitative study.

OBJECTIVE: To explore the perceptions of Chinese older adults with type 2 diabetes mellitus (T2DM) about the WeChat-based self-management mobile health (mhealth) platforms. METHODS: A semi-structured interview was conducted with a purposive sample of 20 older adults with T2DM. Interview data were summarized and refined with the NVivo 11.0 software. Content analysis was used for qualitative research. RESULTS: Three themes emerged from the interviews: Perception One: Better experience when using a self-management mobile platform; Perception Two: More practical functions of the platform; and Perception Three:Trust and assistance from others. CONCLUSION: Older adults with T2DM have a high willingness to use the WeChat-based self-management mhealth platform. To encourage them to use the platform more frequently, the following factors should be taken into consideration: the perceived experience, fundamental demand for self-management, and need for others' support and assistance. These age-appropriate approaches to self-management health reform may benefit older adults with T2DM.

Human Amniotic Epithelial Stem Cells Promote Colonic Recovery in Experimental Colitis via Exosomal MiR-23a-TNFR1-NF-κB Signaling.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, manifests as chronic intestinal inflammation with debilitating symptoms, posing a significant burden on global healthcare. Moreover, current therapies primarily targeting inflammation can lead to immunosuppression-related complications. Human amniotic epithelial stem cells (hAESCs), which exhibit low immunogenicity and ethical acceptability, have gained attention as potential therapeutics. In this study, it is demonstrated that their encapsulation in a hydrogel and administration via anal injection enhanced the colonic mucosal barrier repair in a murine colitis model induced by dextran sodium sulfate during the recovery phase. The underlying mechanism involved the release of exosomes from hAESCs enriched with microRNA-23a-3p, which post-transcriptionally reduced tumor necrosis factor receptor 1 expression, suppressing the nuclear factor-κB pathway in colonic epithelial cells, thus played a key role in inflammation. The novel approach shows potential for IBD treatment by restoring intestinal epithelial homeostasis without the immunosuppressive therapy-associated risks. Furthermore, the approach provides an alternative strategy to target the key molecular pathways involved in inflammation and promotes intestinal barrier function using hAESCs and their secreted exosomes. Overall, this study provides key insights to effectively treat IBD, addresses the unmet needs of patients, and reduces related healthcare burden.

Exercise Adherence and Compliance and Its Related Factors Among Elderly Patients with Type 2 Diabetes in China: A Cross-Sectional Study.

Purpose: To explore exercise adherence and compliance as well as its related factors among elderly patients with type 2 diabetes mellitus (T2DM) to provide a basis for clinical intervention strategies. Patients and Methods: The present study was a cross-sectional study of 205 elderly patients with T2DM who regularly visited a Shanghai community health center from August 2020 to July 2021. Exercise adherence and compliance was measured using an exercise adherence and compliance questionnaire, and potential correlates were explored using multiple linear regression analysis. Results: The mean total score of the exercise adherence and compliance questionnaire was 16.72±5.08. The stepwise regression results revealed that exercise adherence and compliance was positively correlated with self-monitoring (F=3.510, P=0.005), exercise knowledge (r=0.784, P<0.001), exercise willingness (r=0.556, P<0.001), professional support (r=0.426, P<0.001), and self-efficiency (r=0.5, P<0.001). There was a negative correlation between hypoglycemia and exercise adherence and compliance (F=-3.672, P<0.001). Conclusion: Low exercise adherence and compliance was related to low glucose self-monitoring frequency, increased hypoglycemia, less exercise knowledge, less exercise willingness, less professional support, and less self-efficiency. When developing exercise instructions adapted to the cognitive and volitional needs of diabetic patients, it is essential to focus on their daily self-management habits and extrinsic motivation to improve exercise adherence and compliance.

Colorimetric Determination of Hypochlorite Based on the Oxidative Leaching of Gold Nanorods.

Hypochlorite plays a critical role in killing microorganisms in the water. However, it can also cause cardiovascular diseases, neuron degeneration, and cancer to humans. Although traditional methods feature excellent sensitivity and reliability in detecting hypochlorite, the expensive instruments and strict determination conditions have limited their application in environmental analysis to some extent. Thus, it is necessary and urgent to propose a cheap, facile, and quick analytical assay for hypochlorite. This paper proposes a colorimetric assay for hypochlorite utilizing gold nanorods (AuNRs) as the nanoreactor and color reader. The AuNRs were acquired via a reported seed-mediated method. NaClO with strong oxidation property can cause the etching of gold from the longitudinal tips of AuNRs, which could shorten the aspect ratio of AuNRs, decrease the absorption in the UV⁻Vis spectrum and also induce the solution color changing from red to pale yellow. Thus, according to the solution color change and the absorbance of longitudinal surface plasmon resonance of AuNRs, we established the calibration curve of NaClO within 0.08 µM to 125 µM (∆Abs = 0.0547 + 0.004 CNaClO, R² = 0.9631). Compared to traditional method, we obtained the conversion formula between the concentration of residual-chlorine in tap water and the concentration of hypochlorite detected by the proposed colorimetric assay, which is Cresidual-chlorine = 0.24 CNaClO. Finally, the real application of the colorimetric assay in tap water was successfully performed, and the accuracy of the colorimetric method can reach from -6.78% to +8.53%.