Effects of mind-body exercise on cardiopulmonary function, blood pressure, and quality of life in CHD patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is one of the highest mortality diseases in the world, which seriously threatens human health and quality of life (QOL). The purpose of this study is to systematically analyze the effects of mind-body exercise on cardiopulmonary function, blood pressure and QOL in CHD patients, and to provide scientific evidence-based exercise prescription for patients with coronary heart disease. METHODS: This research review will include the following electronic databases from its establishment to December 2020: PubMed, EMBASE, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wanfang. Objective to search randomized controlled trials (RCTs) about the effects of mind-body exercise on cardiopulmonary function, blood pressure and QOL in patients with coronary heart disease. CONCLUSION: This systematic review and meta-analysis will provide strong evidence for the efficacy and safety of mind-body exercise in patients with coronary heart disease. SYSTEMATIC REVIEW REGISTRATION: INPLASY202120016. ETHICS AND DISSEMINATION: Ethical approval will not be necessary since this systematic review and meta-analysis will not contain any private information of participants or violate their human rights.

miR-129-5p Regulates the Immunomodulatory Functions of Adipose-Derived Stem Cells via Targeting Stat1 Signaling.

Adipose-derived stem cells (ASCs) have become one of the most promising stem cell populations for cell-based therapies in regenerative medicine and for autoimmune disorders owing to their multilineage differentiation and immunomodulatory capacities, respectively. One advantage of ASC-based therapy lies in their immunosuppressive potential. However, how to get ASCs to provide consistent immunosuppression remains unclear. In the current study, we found that miR-129-5p was induced in ASCs treated with inflammatory factors. ASCs with miR-129-5p knockdown exhibited enhanced immunosuppressive capacity, as evidenced by reduced expression of proinflammatory factors, with concurrent increased expression of inducible nitric oxide synthases (iNOS) and nitric oxide (NO) production. These cells also had an increased capacity to inhibit T cell proliferation in vitro. ASCs with miR-129-5p knockdown alleviated inflammatory bowel diseases and promoted tumor growth in vivo. Consistently, ASCs that overexpressed miR-129-5p exhibited reduced iNOS expression. Furthermore, we show that miR-129-5p knockdown in ASCs results in hyperphosphorylation of signal transducer and activator of transcription 1 (Stat1). When fludarabine, an inhibitor of Stat1 activation, was added to ASCs with miR-129-5p knockdown, iNOS mRNA and protein levels were significantly reduced. Collectively, these results reveal a new role for miR-129-5p in regulating the immunomodulatory activities of ASCs by targeting Stat1 activation. These novel insights into the mechanisms of ASC immunoregulation may lead to the consistent production of ASCs with strong immunosuppressive functions and thus better clinical utility of these cells.

Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-ß1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

Fisetin improves lead-induced neuroinflammation, apoptosis and synaptic dysfunction in mice associated with the AMPK/SIRT1 and autophagy pathway.

Fisetin, a natural flavonoid found in plants, fruits and vegetables, exerts anti-cancer, anti-oxidant, anti-inflammatory and anti-mitotic effects. The current study instigates the protective effect of fisetin against lead-induced synaptic dysfunction, neuroinflammation and neurodegeneration in mice, and explores its underlying mechanisms. The results indicated fisetin can significantly ameliorated behavioral impairments in Pb-treated mice. Fisetin inhibited Pb-induced the apoptotic neurodegeneration, as indicated by the decreased levels of Bax and cleaved caspase-3. Fisetin suppressed activations of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB and subsequently inactivate pro-inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). It can also decrease the accumulation of p-tau and amyloid-beta (Aß) and increased the expression of the Aß remover neprilysin (NEP) in brains of mice. Fisetin also reversed Pb-induced synaptic dysfunction by increasing the levels of synaptosomal associated protein-25 (SNAP-25), postsynaptic density-95 (PSD-95), cyclic-AMP-response element-binding protein (CREB) phosphorylation and calcium/calmodulin kinase II (CaMKII) phosphorylation. Fisetin promoted Pb-induced autophagy in the brains of mice. Moreover, fisetin can increase levels of the denosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and SIRT1. Fisetin may be developed as a potential nutritional target for the prevention of Pb-induced neurotoxicity.

CKIP-1 regulates the immunomodulatory function of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are self-renewing multipotent cells with immunoregulatory function, which makes them attractive candidates for regenerative medicine. However, the detailed mechanisms of their immunomodulatory capacity are not fully characterized. Here, we found that casein kinase 2 interacting protein-1 (CKIP-1) expression was induced in the murine MSC cell line C3H/10T1/2 by LPS. Knockdown of CKIP-1 did not cause significant differences on the cell cycle or immunophenotype of MSCs. However, MSCs with CKIP-1 knockdown showed enhanced immunosuppressive capacity. Real-time PCR and western blot analyses revealed that compared with the control group, MSCs with CKIP-1-knockdown exhibited higher IL-10 production and p38 MAPK phosphorylation following LPS treatment. Interestingly, the expression of CKIP-1 was decreased in MSCs following high glucose treatment. Furthermore, MSCs became more immunosuppressive after high glucose treatment, as shown by higher IL-10 production and enhanced inhibition of T cell proliferation. Collectively, our data reveal a novel role for CKIP-1 in regulating MSC-mediated immunomodulation, and indicate that MSCs become more immunosuppressive under high glucose conditions. These new insights may help in the development of future applications of MSCs.

Sudden sensorineural hearing loss (SSHL) following a local anesthetic dental procedure.

Acute sensorineural hearing loss is an uncommon phenomenon in dentistry. We describe the case of a 79-year-old male who presented with acute sensorineural hearing loss occurring 2 days after a tooth extraction procedure under local anesthesia. Possible mechanisms are discussed. He was treated with vasodilators (Ginaton and Alprostadil Injection) and Mecobalamin injection with benefit. High dose oral steroids (1 mg/kg) and low molecular weight dextran were used.

Mysm1 epigenetically regulates the immunomodulatory function of adipose-derived stem cells in part by targeting miR-150.

Adipose-derived stem cells (ASCs) are highly attractive for cell-based therapies in tissue repair and regeneration because they have multilineage differentiation capacity and are immunosuppressive. However, the detailed epigenetic mechanisms of their immunoregulatory capacity are not fully defined. In this study, we found that Mysm1 was induced in ASCs treated with inflammatory cytokines. Adipose-derived stem cells with Mysm1 knockdown exhibited attenuated immunosuppressive capacity, evidenced by less inhibition of T cell proliferation, more pro-inflammatory factor secretion and less nitric oxide (NO) production in vitro. Mysm1-deficient ASCs exacerbated inflammatory bowel diseases but inhibited tumour growth in vivo. Mysm1-deficient ASCs also showed depressed miR-150 expression. When transduced with Mysm1 overexpression lentivirus, ASCs exhibited enhanced miR-150 expression. Furthermore, Mysm1-deficient cells transduced with lentivirus containing miR-150 mimics produced less pro-inflammatory factors and more NO. Our study reveals a new role of Mysm1 in regulating the immunomodulatory activities of ASCs by targeting miR-150. These novel insights into the mechanisms through which ASCs regulate immune reactions may lead to better clinical utility of these cells.

Deubiquitinase Mysm1 regulates macrophage survival and polarization.

Macrophages play pivotal roles in innate and adaptive immune response, tissue homeostasis and cancer development. Their development and heterogeneity are tightly controlled by epigenetic program and transcription factors. Deubiquitinase Mysm1 plays crucial roles in regulating stem cell maintenance and immune cell development. Here we show that Mysm1 expression is up regulated during bone marrow macrophage development. Mysm1 deficient cells exhibit accelerating proliferation with more cells going to S phase and higher cyclin D1, cyclin D2 and c-Myc expression. However, compared to WT counterparts, more cell death is also detected in Mysm1 deficient cells no matter M-CSF deprived or not. In LPS-condition medium, Mysm1-/- macrophages show more pro-inflammatory factors IL-1ß, TNFα and iNOS production. In addition, much higher expression of surface marker CD86 is detected in Mysm1-/- macrophages. In vivo tumor model data demonstrate that in contrast to WT macrophages promoting tumor growth, Mysm1-/- macrophages inhibit tumor growth, showing the properties of M1 macrophages. Collectively, these data indicate that Mysm1 is essential for macrophage survival and plays an important role in macrophage polarization and might be a target for cell therapy.

Role of AMPK pathway in lead-induced endoplasmic reticulum stress in kidney and in paeonol-induced protection in mice.

Paeonol is a natural flavonoid isolated from Moutan Cortex, which has been found to exhibit antioxidant, anti-apoptotic, anti-aging and anti-inflammatory bioactivities. Herein, we investigated the nephroprotective efficacy of paeonol against Pb-induced toxicity and elucidated the potential mechanisms. The results revealed that paeonol significantly ameliorated renal dysfunction and histology changes of Pb-treated mice. Paeonol inhibited oxidative stress and increased activities of antioxidant enzyme in the kidneys of Pb-treated mice. Paeonol decreased the nuclear factor-κB activation and over-production of inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Paeonol suppressed endoplasmic reticulum (ER) stress in kidneys of in the Pb treatment group and primary kidney mesangial cells. Moreover, paeonol increased the denosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased the activations of glycogen synthase kinase-3 (GSK-3), protein kinase RNA-like ER kinase (PERK), inositol-requiring protein-1 (IRE1), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). These results were further confirmed in primary kidney mesangial cells. Taken together, these findings indicate that paeonol could protect kidney form Pb-induced injury by inhibiting oxidative stress, ER stress and inflammation via the AMPK and GSK-3 pathway. Paeonol might be a potential therapeutic agent to inhibit ER stress-associated inflammation in lead-stimulated kidneys.

Dihydromyricetin Inhibits Lead-Induced Cognitive Impairments and Inflammation by the Adenosine 5'-Monophosphate-Activated Protein Kinase Pathway in Mice.

Dihydromyricetin (DHM), a natural flavonoid derived from the medicinal and edible plant Ampelopsis grossedentata, exhibits antioxidant, antiapoptosis, antitumor, and anti-inflammatory bioactivities. This study evaluated the effects of DHM on Pb-induced neurotoxicity and explored the underlying mechanisms. DHM significantly ameliorated behavioral impairments of Pb-induced mice. It decreased the levels of lipid peroxidation and protein carbonyl and increased the activities of superoxide dismutase and catalase in the brains. DHM suppressed Pb-induced apoptosis, as indicated by the decreased levels of Bax and cleaved caspase-3. DHM also decreased inflammatory cytokines in the brains of Pb-treated mice. DHM decreased amyloid-beta (Aß) level and nuclear factor-κB nuclear translocation. Moreover, DHM induced the adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the activation of p38, Toll-like receptor 4, myeloid differentiation factor 88, and glycogen synthase kinase-3. Collectively, this is the first report indicating that DHM could improve Pb-induced cognitive functional impairment by preventing oxidative stress, apoptosis, and inflammation and that the protective effect was mediated partly through the AMPK pathway.

Vitrification solution containing DMSO and EG can induce parthenogenetic activation of in vitro matured ovine oocytes and decrease sperm penetration.

This study was designed to examine the reduced incidence of normal fertilization in vitrified ovine oocytes. After in vitro maturation for 24 h, the oocytes were randomly allocated into three groups: (1) untreated (control), (2) exposed to vitrification solution (VS) without being plunged into liquid nitrogen (toxicity), or (3) vitrified by open-pulled straw method (vitrification). In experiment 1, the treated and control oocytes were matured for another 2 h, and the oocytes were then in vitro fertilized for 12 h to examine sperm penetration. The percentage of monospermy in toxicity group (29.3%) and vitrification group (28.2%) dramatically decreased compared to the control group (45.0%) (P<0.05). To find the mechanism that the VS decreased the monospermy, some treated and control oocytes were used to test the distribution of CG and the resistance of zona pellucida (ZP) to 0.1% pronase E immediately (IVM 24 h), after another 2 h of maturation (IVM 26 h), and after 12 h of in vitro fertilization (IVF 12 h) respectively. Others were used to examine female pronucleus formation after 12 h of culture in fertilization medium with the absence of sperm. The results showed that the percentage of CG completely release in the oocytes (IVM 24 and 26 h) of toxicity group (41.2% and 39.9%) and vitrification group (41.7% and 51.7%) was significantly higher than that of control group (7.1% and 18.4%) (P<0.05). The ZP digestion duration in the oocytes (IVM 26 h) of the toxicity group (435.6 s) and vitrification group (422.3 s) was longer than that of control group (381.6 s) (P<0.05). The percentage of female pronucleus formation in toxicity group (58.7%) and vitrification group (63.9%) was higher than that (8.2%) of control group (P<0.05). The data above demonstrated that the VS containing DMSO and EG could parthenogenetically activate in vitro matured ovine oocytes, resulting in ZP hardening and decreased sperm penetration.

The IGF2 receptor is a USF2-specific target in nontumorigenic mammary epithelial cells but not in breast cancer cells.

The antiproliferative activities of the USF proteins and the frequent loss of USF function in cancer cells suggest a role for these ubiquitous transcription factors in tumor suppression. However, the cellular targets that mediate the effects of USF on cellular proliferation and transformation remain uncharacterized. IGF2R, with multiple functions in both normal growth and cancer, was investigated here as a possible USF target in both nontumorigenic and tumorigenic breast cell lines. The 5'-flanking sequences of the human IGF2R gene contain multiple, highly conserved E boxes almost identical to the consensus USF DNA-binding sequence. These E boxes were found to be essential for IGF2R promoter activity in the nontumorigenic mammary epithelial cell line MCF-10A. USF1 and USF2 bound the IGF2R promoter in vitro, and both USF1 and USF2, but not c-Myc, were present within the IGF2R promoter-associated chromatin in vivo. Overexpressed USF2, but not USF1, transactivated the IGF2R promoter, and IGF2R mRNA was markedly decreased by expression of a USF-specific dominant negative mutant, identifying IGF2R as a USF2 target. IGF2R promoter-driven expression was USF-independent in both MCF-7 and MDA-MB-231 breast cancer cell lines, suggesting that a defect in USF function may contribute to down-regulation of IGF2R expression in cancer cells.