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The high radiosensitivity of the intestinal epithelium limits the survival of victims by nuclear accidents or terrorism and limits effective radiotherapy against abdominal malignancies. Recently, we reported that (−)-epicatechin (EC) modulates oxidative stress and exerts neuroprotection. Here, we investigate the protective effects of EC against intestinal damage induced by radiation. The established model is acute moderate but reversible intestinal injury damage. We also set up the injured model of "minigut" ex vivo, which mimic the process of intestinal regeneration in vivo. We found that EC can repress oxidative stress by regulating SOD and MDA levels in serum and intestine tissue. Correspondingly, EC can decrease apoptosis of crypt cells in Lgr5-EGFP-IRES-creERT2 mice after radiation. Further studies demonstrated that EC can promote Nrf2 translocation from cytoplasm to nuclear and then activate the expression of HO1 and NQO1. Interestingly, EC can enhance the activity of intestine stem cells labelled by Lgr5 and promote intestinal epithelium regeneration determined by HE and immunofluorescence staining in vivo and in vitro. We also found that EC can activate the Wnt/β-catenin signal pathway confirmed by TCF/LEF luciferase reporter assay. Together, EC can provide the protective effect on intestine and promote intestinal regeneration after radiation through Nrf2 and Wnt/β-catenin signal pathway. [ABSTRACT FROM AUTHOR]

Chimeric RNAs are transcripts composed of RNA fragments from different genes and are traditionally well-known cancer-causing genetic events. Recent studies show chimeric RNAs being present in multiple non-neoplastic tissues and cells, suggesting that at least some may have roles in normal physiology. However, chimeric RNAs and their implications in brain development and neural differentiation have not been formally studied. Here, we firstly characterized the landscape of chimeric RNAs in human infant brain tissues and identified 599 chimeric RNAs. Through a series of filtering, 22 were selected and tested in a neural differentiation process starting from stem cells. Ten were validated experimentally. One of these ten chimeric RNAs, DUS4L-BCAP29 , dramatically increased when human umbilical mesenchymal stem cells were induced for neural differentiation. Consistently, we found that overexpressed DUS4L-BCAP29 effectively promoted neural differentiation. Our results support the important role(s) chimeric RNAs play in neural differentiation, and are consistent with the new notion that chimeric RNAs also exist in normal physiology, and likely serve biological purposes. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) are defined as non‑coding transcripts (>200 nucleotides) that serve important roles in the proliferation and differentiation of stem cells. Hair follicle stem cells (HFTs) have multidirectional differentiation potential and are able to differentiate into skin, hair follicles and sebaceous glands, serving a role in skin wound healing. The aim of the present study was to analyze the regulatory role of lncRNA AK015322 (IncRNA5322) in HFTs and the potential mechanism of IncRNA5322‑mediated differentiation of HFTs. The results demonstrated that lncRNA5322 transfection promoted proliferation and differentiation in HFTs. It was identified that lncRNA5322 transfection upregulated the expression and phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) in HFTs. It was also observed that lncRNA5322 transfection upregulated microRNA (miR)‑21 and miR‑21 agonist (agomir‑21) eliminated lncRNA5322‑induced expression and phosphorylation of PI3K and AKT. The present study also demonstrated that agomir‑21 blocked IncRNA5322‑induced expression and phosphorylation of PI3K and AKT in HFTs. The results indicated that agomir‑21 transfection also suppressed the IncRNA5322‑induced proliferation and differentiation of HFTs. In conclusion, the results of the present study suggest that lncRNA5322 is able to promote the proliferation and differentiation of HFTs by targeting the miR‑21‑mediated PI3K‑AKT signaling pathway in HFTs. [ABSTRACT FROM AUTHOR]

2 rhMG53 lessens H2O2-induced oxidative injury to hUC-MSCs and promotes cell migration. a Representative images of hUC-MSCs with and without 200 M H2O2 treatment. b Time- and dose-dependent effects of H2O2 on hUC-MSCs. Two hundred micromolar H2O2 was used for subsequent experiments to induce hUC-MSC oxidative damage. c Dose-dependent effects of MG53 on hUC-MSCs. [Extracted from the article]

[Display omitted] • Bomidin is a new recombinant antimicrobial peptide AMP derived from BMAP-27. • Bomidin mediates Keap1 protein degradation, enhancing Nrf2 nuclear translocation. • Bomidin can suppress ferroptosis, further relieving periodontitis. • Bomidin is a promising medicine for periodontitis. Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin–proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin–proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. Methods: In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. Results: We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling. Conclusion: MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury. [ABSTRACT FROM AUTHOR]

Sepsis is characterized as exceed inflammation response and multiple organs dysfunction. Many articles suggested that mesenchymal stem cells can alleviate the inflammation and improve the survival rate of inflammatory animal models, however, the mechanism is still unclear. This study aimed to test the hypothesis that rat adipose-derived mesenchymal stem cells (ADMSCs) produce a amount of soluble tumour necrosis factor receptor 1 (sTNFR1), which ameliorated liver injury and inflammation and increased the survival rate of septic rat model.120 adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated (Sham), sepsis-induced by cecal ligation and puncture (CLP), shNC (injected 1 × 106 ADMSCs with transfected with scramble shRNA 1 h after CLP), and shsTNFR1 (injected 1 × 106 ADMSCs with transfected with sTNFR1 1 h after CLP). The serum sTNFR1 levels were the lowest in Sham and highest in shNC group. ADMSCs could decrease the levels of pro-inflammatory cytokines such as TNF-α, IL-6, AP-1 c-jun and NF-κB p56 after CLP administration, whereas this result was weaken by shsTNFR1 administration. Moreover, shNC had an increased levels of the anti-inflammatory factor IL-10 compared with CLP, and this change could be weakened in shsTNFR1 administration. More importantly, ADMSCs could improve the survival rate of CLP-induced septic rats. Therapeutically administered ADMSCs secrete sTNFR1, which alleviated the liver injury and inflammatory response. Additionally, ADMSCs also ameliorated the systematic inflammation and increased the survival rate of septic rats. • ADMSCs could produce numerous sTNFR1 under inflammatory stimulation. • ADMSCs transplanted into the injury organ, liver. • ADMSCs could alleviate the liver injury and inflammation via secreting sTNFR1. [ABSTRACT FROM AUTHOR]