Staging reinterventions for remodeling of residual aortic dissection: a single-center retrospective study.

Objective: Inadequate remodeling of residual aortic dissection (RAD) following repair of Stanford A or B aortic dissections has been identified as a significant predictor of patient mortality. This study evaluates the short- to mid-term outcomes of staged reinterventions for RAD at a single center with prospective follow-up. Methods: Data were retrospectively collected from patients with RAD who underwent staged reinterventions or received none-surgery treatment in the Cardiovascular Surgery Department of our hospital between July 2019 and December 2021. The cohort included 54 patients with residual distal aortic dissection post-primary surgery, comprising 28 who underwent open surgery and 26 who received thoracic endovascular aortic repair (TEVAR). Patients were divided into two groups: those who underwent staged stent interventions for distal dissection [staged reintervention (SR) group] and those who did not undergo surgery (non-surgery group). For the SR group, second or third staged stent interventions were performed. The study assessed distal remodeling of aortic dissection between the groups, focusing on endpoints such as mortality (both general and aortic-specific), occurrences of visceral branch occlusion, necessity for further interventions, and significant adverse events. Morphological changes were analyzed to determine the therapeutic impact. Results: The study encompassed 54 participants, with 33 in the SR group and 21 in the non-surgical control group. Baseline demographics and clinical characteristics were statistically comparable across both groups. During an average follow-up of 31.5 ± 7.0 months, aortic-related mortality was 0% in both groups; all-cause mortality was 3% (one case) and 5% (one case) in the SR and control groups, respectively, with no statistically significant difference noted. In the SR group, a single patient experienced complications, including renal artery thrombosis, leading to diminished blood flow. An increased true lumen (TL) area and a decreased false lumen area at various aortic planes were observed in the SR group compared to the control group. Conclusion: The staged reintervention strategy for treating RAD is safe and provides promising early results.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Croceicoccus gelatinilyticus sp. nov., isolated from a tidal flat sediment.

A novel Gram-staining-negative and short-rod-shaped bacterial strain designated as 1NDH52T was isolated from a tidal flat sediment and characterized using a polyphasic taxonomic approach. The predominant cellular fatty acids of strain 1NDH52T were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C14:0 2-OH; the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid; the major respiratory quinone was Q-10. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 1NDH52T was closely related to type strains Croceicoccus sediminis S2-4-2 T (98.9%), Croceicoccus bisphenolivorans H4T (98.9%) and Croceicoccus pelagius Ery9T (98.7%). Phylogenomic analysis indicated that strain 1NDH52T formed an independent branch distinct from all type strains of this genus. The overall genome related indices including the digital DNA-DNA hybridization values, average nucleotide identities and average amino acid identities between strain 1NDH52T and the three close relatives above indicated that strain 1NDH52T should represent a novel genospecies. The genomic DNA G + C content was 62.6%. Strain 1NDH52T could produce carotenoids and its genome contained the complete carotenoids biosynthetic gene cluster. Based on the phenotypic and genotypic characteristics, strain 1NDH52T is concluded to represent a novel species of the genus Croceicoccus, for which the name Croceicoccus gelatinilyticus sp. nov., is proposed. The type strain of the species is 1NDH52T (= GDMCC 1.2381 T = KCTC 82668 T).

Hypoxic ucMSC-secreted exosomal miR-125b promotes endothelial cell survival and migration during wound healing by targeting TP53INP1.

A hypoxic microenvironment is a common feature of skin wounds. Our previous study demonstrated that three-dimensional coculture of umbilical cord-derived mesenchymal stem cells (ucMSCs) and endothelial cells facilitates cell communication and host integration in skin tissue engineering. Here, we aimed to identify the mechanism by which ucMSCs affect endothelial cells under hypoxic conditions after skin injury. We demonstrate that hypoxia enhances the exosome-mediated paracrine function of ucMSCs, which increases endothelial cell proliferation and migration. In a mouse full-thickness skin injury model, ucMSC-derived exosomes can be taken up by endothelial cells and accelerate wound healing. Hypoxic exosomes lead to a better outcome than normoxic exosomes by promoting proliferation and inhibiting apoptosis. Mechanistically, microRNA-125b (miR-125b) transcription is induced by hypoxia in ucMSCs. After being packaged into hypoxic exosomes and transported to endothelial cells, miR-125b targets and suppresses the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1) and alleviates hypoxia-induced cell apoptosis. Inhibition of miR-125b-TP53INP1 interaction attenuates the protective effect of hypoxic exosomes. Moreover, artificial agomiR-125b can accelerate wound healing in vivo. Our findings reveal communication between ucMSCs and endothelial cells via exosomal miR-125b/TP53INP1 signaling in the hypoxic microenvironment and present hypoxic exosomes as a promising therapeutic strategy to enhance cutaneous repair.

Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization.

Traumatic hemorrhagic shock (THS) is a major cause of mortality and morbidity worldwide in severely injured patients. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and tissue repair potential mainly through a paracrine pathway mediated by MSC-derived extracellular vesicles (MSC-EVs). Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine that plays a crucial role during the inflammatory response, with a broad range of effects on innate and adaptive immunity, preventing damage to the host and maintaining normal tissue homeostasis. However, the function and mechanism of IL-10 in MSC-mediated protective effect in THS remain obscure. Here, we show that MSCs significantly attenuate hepatic injury and inflammation from THS in mice. Notably, these beneficial effects of MSCs disappeared when IL-10 was knocked out in EVs or when recombinant IL-10 was administered to mice. Mechanistically, MSC-EVs function to carry and deliver IL-10 as cargo. WT MSC-EVs restored the function of IL-10 KO MSCs during THS injury. We further demonstrated that EVs containing IL-10 mainly accumulated in the liver during THS, where they were captured by Kupffer cells and induced the expression of PTPN22. These effects subsequently shifted Kupffer cells to an anti-inflammatory phenotype and mitigated liver inflammation and injury. Therefore, our study indicates that MSC-EVs containing IL-10 alleviate THS-induced hepatic injury and may serve as a cell-free therapeutic approach for THS.

miR-210 Participates in Hepatic Ischemia Reperfusion Injury by Forming a Negative Feedback Loop With SMAD4.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (IR) injury is a major complication of liver transplantation, resection, and hemorrhagic shock. Hypoxia is a key pathological event associated with IR injury. MicroRNA-210 (miR-210) has been characterized as a micromanager of hypoxia pathway. However, its function and mechanism in hepatic IR injury is unknown. APPROACH AND RESULTS: In this study, we found miR-210 was induced in liver tissues from patients subjected to IR-related surgeries. In a murine model of hepatic IR, the level of miR-210 was increased in hepatocytes but not in nonparenchymal cells. miR-210 deficiency remarkably alleviated liver injury, cell inflammatory responses, and cell death in a mouse hepatic IR model. In vitro, inhibition of miR-210 decreased hypoxia/reoxygenation (HR)-induced cell apoptosis of primary hepatocytes and LO2 cells, whereas overexpression of miR-210 increased cells apoptosis during HR. Mechanistically, miR-210 directly suppressed mothers against decapentaplegic homolog 4 (SMAD4) expression under normoxia and hypoxia condition by directly binding to the 3' UTR of SMAD4. The pro-apoptotic effect of miR-210 was alleviated by SMAD4, whereas short hairpin SMAD4 abrogated the anti-apoptotic role of miR-210 inhibition in primary hepatocytes. Further studies demonstrated that hypoxia-induced SMAD4 transported into nucleus, in which SMAD4 directly bound to the promoter of miR-210 and transcriptionally induced miR-210, thus forming a negative feedback loop with miR-210. CONCLUSIONS: Our study implicates a crucial role of miR-210-SMAD4 interaction in hepatic IR-induced cell death and provides a promising therapeutic approach for liver IR injury.