Notes

Your Predictors of Harshness of Lymphosclerosis within Extremity Lymphedema.
Compared with normal group, miR-30a-5p in model groups were down-regulated, while Becn1 expression was significantly up-regulated, with slower proliferation, higher apoptosis rate, lower SOD level, and significantly higher ROS, MDA, IL-6, and TNF-α levels (all P<0.05). Overexpression of miR-30a-5p or Becn1 knock-out could lower Becn1 expression, apoptosis rate, promote proliferation, with relatively higher SOD level and lower ROS, MDA, Il-6, and TNF-α levels of model cells (all P<0.05).

Up-regulation of miR-30a-5p can suppress the expression of Becn1 to increase the growth and inhibit the apoptosis of immortalized rat podocyte cell line, therefore ameliorating podocyte injury induced by high glucose in vitro.
Up-regulation of miR-30a-5p can suppress the expression of Becn1 to increase the growth and inhibit the apoptosis of immortalized rat podocyte cell line, therefore ameliorating podocyte injury induced by high glucose in vitro.This study was aimed to determine the role of has-miR-155 and E2F2 on corneal endothelial cells. Real-time quantitative PCR and Western blot assays were carried out to determine the levels of has-miR-155 and E2F2, and Flow cytometry assay was conducted to detect cell cycle. In addition, Targetscan7.2 was adopted to analyze the internal connection between hsa-miR-155 and E2F2, and a dual luciferase reporter gene assay to determine predicted site between has-miR-155 and E2F2. Increased hsa-miR-155 resulted in decreased E2F2, while decreased hsa-miR-155 increased the level of E2F2. In addition, both increased hsa-miR-155 and decreased E2F2 led to an increase in S-phase cells and a decrease in G1-phase cells. Also, they induced an increase in the activity of barrier-related proteins MLCK and ZO-1, an up-regulation of Cyclin D1 and Cyclin E1, and a down-regulation of apoptosis proteins (Caspase 3/Bax/Bim/Bid) whereas decreased hsa-miR-155 led to an opposite change in cells, and decreased E2F2 could offset cell changes caused by increased has-miR-155. In conclusion, Has-miR-155 regulates the cell cycle of corneal endothelial cells and improves their barrier function by down regulating E2F2.Leukemias driven by chromosomal translocation of the mixed-lineage leukemia (MLL) gene are highly prevalent in hematological malignancy. The poor survival rate and lack of effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. The present study aimed to investigate the potential effectiveness and mechanism of Anlotinib, a novel receptor tyrosine kinase inhibitor, in MLL-r acute myeloid leukemia (AML). The findings revealed that Anlotinib significantly inhibited the growth of MLL-r AML cells in both in vivo and a murine xenograft model. RNA sequencing identified that multiple genes involved in DNA damage response were responsible for Anlotinib activity. To further elucidate the correlation between the DNA damage response induced by Anlotinib and MLL fusion, Gene Expression Profiling Interactive Analysis (GEPIA) was conducted. It revealed that Anlotinib impaired DNA damage response via inhibiting SETD1A and AKT. In conclusion, Anlotinib exerts anti-leukemia function by inhibiting SETD1A/AKT-mediated DNA damage response and highlights a novel mechanism underlying Anlotinib in the treatment of MLL-r AML.
Astaxanthin (ATX) is a carotenoid pigment with effective antioxidant, anti-inflammatory, antitumor and immunomodulatory actions. ATX has been proposed to exert neuroprotective effects and attenuate oxidative stress in mice after traumatic brain injury (TBI). The nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway is stimulated after TBI and activates a compensatory mechanism against TBI. Nevertheless, the effect of ATX on the pathophysiology of TBI in mice is limited. Our present study evaluated the neuroprotection afforded by ATX and the possible role of the Nrf2/HO-1 pathway in experimental TBI.

Mice were casually separated into 3 groups the sham, TBI + vehicle, and TBI + ATX (100 mg/kg, intraperitoneally administered) groups. Neurobehaviors of the mice were assessed using the neurological severity scores (NSSs), the forced swimming test (FST) and the rotarod test. Levels of the Nrf2, HO-1, NAD(P)H quinine oxidoreductase-1 (NQO1), cleaved caspase3 (C-caspase3), and superoxide dismutase1 (SOD1) proteins and levels of the Nrf2 and HO-1 mRNAs were assessed. In addition, Nrf2 nuclear import and apoptosis were measured after TBI.

The ATX treatment significantly improved the neurological status, promoted Nrf2 activation, and upregulated the expression of the Nrf2 and HO-1 mRNAs and the levels of the Nrf2, HO-1, and NQO1 proteins after TBI. The level of the SOD1 protein was decreased after TBI and increased after ATX treatment; however, the difference was not significant. ATX markedly reduced the level of the C-caspase3 protein and the number of TUNEL-positive cells, indicating that it exerted an antiapoptotic effect. Immunofluorescence staining confirmed that ATX promoted Nrf2 nuclear import.

Based on our study, ATX possibly affords neuroprotection by activating the Nrf2/HO-1 signaling pathway in mice after TBI.
Based on our study, ATX possibly affords neuroprotection by activating the Nrf2/HO-1 signaling pathway in mice after TBI.Previous studies have indicated that the generation of newborn hippocampal neurons is impaired in the early phase of Alzheimer's disease (AD). A potential therapeutic strategy being pursued for the treatment of AD is increasing the number of newborn neurons in the adult hippocampus. Recent studies have demonstrated that ginkgo biloba extract (EGb 761) plays a neuroprotective role by preventing memory loss in many neurodegenerative diseases. However, the extent of EGb 761's protective role in the AD process is unclear. In this study, different doses of EGb 761 (0, 10, 20, and 30 mg/kg; intraperitoneal injections once every day for four months) were tested on 5×FAD mice. After consecutive 4-month injections, mice were tested in learning memory tasks, Aβ, and neurogenesis in the dentate gyrus (DG) of hippocampus and morphological characteristics of neurons in DG of hippocampus. Results indicated that EGb 761 (20 and 30 mg/kg) ameliorated memory deficits. Further analysis indicated that EGb 761 can reduce the number of Aβ positive signals in 5×FAD mice, increase the number of newborn neurons, and increase dendritic branching and density of dendritic spines in 5×FAD mice compared to nontreated 5×FAD mice. It was concluded that EGb 761 plays a protective role in the memory deficit of 5×FAD mice.Pulmonary vascular remodeling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is the main characteristic of pulmonary arterial hypertension (PAH). CXCR4 is a specific stem cell surface receptor of cytokine CXCL12 which could regulate homing of hematopoietic progenitor cells and their mobilization. There is evidence that bone marrow-derived CXCR4 proangiogenic cell accumulation take an important part in the development of pulmonary arterial hypertension; however, the underlying mechanisms still remain unknown. Here, we explored the expression profile of CXCR4 both in hypoxia rats and PAH patients by measuring proliferation and migration of PASMCs. We performed western blot analysis to detect downstream molecules. We demonstrated that CXCR4 expression level was increased in both rats exposed to chronic hypoxia and PAH patients in reconstructed pulmonary arterioles. The inhibition of CXCR4 expression slowed down the process of hypoxic-PAH by reducing the mean right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in vivo experimental mode. CXCR4 overexpression and inhibition regulated the cell growth of PASMCs in hypoxia condition, which are the critical cellular events in vascular disease. Furthermore, activation of β-catenin signaling and upregulation of CXCR4 could be blocked by AMD3100 both in vivo and vitro. Taken together, inhibition of CXCR4 expression could downregulate β-catenin, reduced pulmonary artery smooth muscle cell proliferation, and ameliorated pulmonary vascular remodeling in hypoxia rats. These findings suggest that CXCL12/CXCR4 is critical in driving PAH and uncover a correlation between β-catenin dependent signaling.Acute kidney injury (AKI) is defined by rapid deterioration of renal function, and is a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for damaged tissue repair. Platelet rich plasma (PRP) regulates mesenchymal cells to repair tissue damage through the release of growth factors. In this study, we proposed a possible therapeutic use of MSCs stimulated by platelet-rich plasma (PRP-MSCs) in a glycerin-induced AKI murine model. In vivo and in vitro studies, showed that PRP-MSCs could significantly attenuate serum blood urea nitrogen and creatinine levels, and reverse the histopathological kidney damage. PRP-MSCs treatment reduced renal tubular cell apoptosis stimulated by glycerin. We confirmed that PRP promoted the proliferation and reinforced the stemness of MSCs by inducing YAP nucleus expression, and that PRP promoted MSCs exosomes in a paracrine manner to repair AKI through an activated AKT/Rab27 pathway. Our results revealed that the PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced AKI. Therefore, PRP pretreatment may be a new method to improve the therapeutic effect of MSCs.Sepsis-induced myocardial dysfunction (SIMD) is one of the leading causes of death in sepsis. We hypothesized that exosomes released from ECs exposed to bacterial lipopolysaccharides (LPS) have some regulatory effect on cardiomyocytes (CMs). In this study, cultured rat ECs were exposed to 0.5 µg/ml of LPS, and exosomes were isolated from the conditioned medium through ultra-high-speed centrifugation. The exosomes were given to the cultured neonatal rat CMs to test the potential effects and proceed to small RNA sequencing to identify their miRNA expression. We found exosomes from ECs under LPS stimulation (LPS-EC-Exo) enhanced the cell viability and attenuated the injury of CMs. The RNA sequencing depicted the expression of several miRNAs increased in LPS-EC-Exo compared with the exosomes from the control ECs (NC-EC-Exo). buy K-Ras(G12C) inhibitor 9 Further analysis showed that some miRNAs could promote the survival of CMs by down-regulating the expression of apoptosis-related proteins such as BAK1, P53, and PTEN. This study showed that LPS-EC-Exo has a cardiac protective effect on CMs, which miRNAs may achieve.Atherosclerosis is a chronic inflammatory disease driven by lipids, which occurs preferentially in the branches or curved areas of the middle and large arteries, contributing to increased morbidity and mortality of cardiovascular disease. Recently, it has been reported that STAT5 and its regulated immune response are closely related to non-tumor diseases. However, the role of STAT5 in the development of atherosclerosis remains unknown. In this study, atherosclerosis was induced by high-fat diet (HFD) in ApoE-/- mice, and STAT5-IN-1, a STAT5 inhibitor, was orally given. Macrophages stimulated by oxLDL were used as cell models in vitro. The effects of STAT5-IN-1 in ApoE-/- mice induced by HFD were assessed, and the underlying mechanisms were investigated by siRNA-induced gene silencing. The results revealed that treatment with STAT5 inhibitor significantly attenuated atherosclerosis in ApoE-/- mice induced by HFD via decreasing inflammation. Furthermore, it was demonstrated that inhibiting STAT5 could decrease oxLDL-induced inflammation.
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