Xudickson0798

Although inflammation and emphysema in patients with chronic obstructive pulmonary disease (COPD) can be ameliorated by antibiotics such as erythromycin, the impact of drug resistance is still controversial. We aimed to evaluate the role of F528, a new macrolide derivative without antibacterial effect, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model, as well as in a macrophage cell line. The inflammatory cell number and cell type in the BALF were counted, and the levels of cytokines in the BALF and cultured cell medium were measured by ELISA. The degree of emphysema and apoptosis was evaluated by H&E and immunohistochemical staining, respectively. The lung function of the mice was evaluated by a small animal lung function meter. Furthermore, the expression levels of MMP-2, MMP-9, and phospho-NF-κB in the cells and lung tissue were measured by Western blot and qRT-PCR. HO-3867 ic50 In the BALF of the CS-induced pulmonary inflammation and emphysema model, the numbers of inflammatory cells and cytokines were significantly decreased after F528 intervention. F528 intervention also significantly protected lung function from CS-induced emphysema, while the mean lining interception (MLI) of the F528-treated CS group was significantly lower than that of the vehicle-treated CS group. In addition, F528 treatment reduced the phosphorylation of NF-κB induced by smoke, and the expression of MMP-2 and MMP-9 was also obviously decreased by F528 treatment. We therefore conclude that F528 reduces cigarette smoke-induced inflammation and emphysema in vivo and in vitro through inhibition of the activation of NF-κB.

Correlation of SARS-CoV-2 serum antibodies with COVID-19 development and outcome has not been fully studied. Due to the time dynamic of antibodies, the antibody concentration of the same patient varies greatly at different times during the course of the disease. Therefore, our study used IgM/T or IgG/T (the ratio of serum antibody concentration to days after symptom onset) to reflect the patient's humoral immune status, and analyzed their correlation with COVID-19 development and outcome.

Clinical data of 50 non-critical COVID-19 patients were retrospectively analyzed. Time-resolved fluorescence immunochromatography was used to quantitatively detect SARS-CoV-2 IgM and IgG. Correlation analysis was performed.

IgM antibody was positive on day 5 of symptom onset, increased within 2 weeks, and then gradually decreased. However, IgG antibody was positive on week 2 of symptom onset and continued to increase since. Additionally, IgM/T, but not IgG/T of recovery period (Spearman ρ=0.17; P=0.283), was negatively correlated with disease course in 2 weeks of symptom onset (Spearman ρ=-0.860; P=0.000). IgG/T of recovery period was positively correlated with clinical classification (Spearman ρ=0.432; P=0.004), number of involved lung lobes (Spearman ρ=0.343; P=0.026), and lung lesions (Spearman ρ=0.472; P=0.002).

Within 2 weeks of symptom onset, higher IgM/T indicates faster recovery and shorter disease course. In recovery period, higher IgG/T suggests more serious disease. IgM/T or IgG/T may predict disease severity and outcome in non-critical COVID-19 patients.

Within 2 weeks of symptom onset, higher IgM/T indicates faster recovery and shorter disease course. In recovery period, higher IgG/T suggests more serious disease. IgM/T or IgG/T may predict disease severity and outcome in non-critical COVID-19 patients.

This study aimed to explore the value of layer-specific strain analysis by two-dimensional speckle tracking imaging (2D-STI) in the assessment of myocardial toxicity in breast cancer patients receiving anthracycline chemotherapy.

Thirty-four breast cancer patients receiving anthracycline chemotherapy were prospectively enrolled. Conventional echocardiography and 2D-STI were evaluated at baseline after the third and sixth cycles of anthracycline chemotherapy. The strains of different layers of left ventricle (LV) including peak systolic longitudinal strain (endo-LS, mid-LS, epi-LS) and circumferential strain (endo-CS, mid-CS, epi-CS) were measured using EchoPAC analysis software. Peak systolic longitudinal strain (MV-LS, PM-LS, AP-LS), circumferential strain (MV-CS, PM-CS, AP-CS) and radial strain (MV-RS, PM-RS, AP-RS) were measured at mitral valve, papillary muscle and apex levels of LV respectively. Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and lefat valuable to guiding clinical early intervention and improving prognosis.

Layer-specific strain analysis by 2D-STI technology can quantitatively analyze global and regional functions of LV. The myocardial toxicity due to anthracycline chemotherapy can be detected by layer-specific LS of LV in early stage, which is great valuable to guiding clinical early intervention and improving prognosis.Ischemic stroke is the main cause of disability and mortality in the world. Clinical studies have shown that patients who undergo mild transient ischemic attack (TIA) before more severe ischemic stroke have lower clinical severity of stroke and better functional prognosis. This phenomenon is called ischemic preconditioning (IPC). IPC is a powerful intrinsic protection of the brain against ischemic injury, but the underlying mechanism of IPC-mediated endogenous protection of the brain is not clear.

Using transcriptome method, we sequenced the serum of 3 stroke patients with progenitor TIA and 3 stroke patients without prodromal TIA. We explored the expression profiles of miRNAs and mRNAs in response to IPC, and predicted the regulatory pathway of IPC related genes and their expression in cerebral neurons. The methylation consistent expression of IPC-related gene ATP2B1 in blood and brain and alternative polyadenylate (APA) analysis were used to identify the pathway and molecular mechanism of endogenous neuroprotection of IPC.

We found that the brain protective effect of IPC was related to platelet homeostasis and Ca

concentration. IPC-related gene ATP2B1 was highly expressed in γ-aminobutyric acid (GABA)-containing neurons in the brain. From the mechanism, we speculated that ATP2B1 was representative of the same methylation in blood and brain and was affected by alternative polyadenylation.

We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca

concentration in platelet homeostasis pathway and the activation of GABAB receptor.

We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca2+ concentration in platelet homeostasis pathway and the activation of GABAB receptor.Acute kidney injury (AKI) is a common clinical implication with increased tissue damage, uncontrolled immune responses, and risk of mortality, in which ischemia-reperfusion injury (IRI) is one of the leading causes. As critical role for metabolic remodeling in inflammation, Irg1-itaconate axis has received much attention for its immunomodulation in the control of the inflammation. However, its role in the AKI and IRI remains unknown. Here, we found that Irg1 expression was negatively correlated with the expression of inflammatory cytokines during ischemia-reperfusion injury. And Irg1 deficiency promotes renal inflammation and ischemia-reperfusion injury in vivo. Itaconate treatment promoted the survival of WT mice from lethal ischemia and protected against renal IRI and systemic inflammation. Mechanistically, dimethyl itaconate protected renal cells from oxidative stress and prevented macrophage activation by enhancing the translocation of Nrf2 into the nuclei. Our study highlighted the importance of the Irg1-itaconate axis in the protecting against ischemia-reperfusion injury and acute kidney injury, providing potential therapeutic targets to control AKI.Increasing evidence has confirmed long non-coding RNAs (lncRNAs) as important regulators involved in several pathophysiological processes in many diseases. The aim of this study was to investigate the roles of lncRNA ZEB2-AS1 (ZEB2-AS1) in osteosarcoma (OS). The levels of ZEB2-AS1 in OS tissues and cells were detected using RT-PCR. The clinical significance of ZEB2-AS1 expressions in OS patients was statistically analyzed. The functional effects of ZEB2-AS1 on the proliferation, apoptosis, invasion, and metastasis of OS cells was determined by a series of cellular experiments. Bioinformatic analysis, dual-luciferase reporter assays and pull-down assays were carried out for the confirmation of the molecular binding. We found that ZEB2-AS1 expression was distinctly upregulated in OS specimens and cell lines. Higher levels of ZEB2-AS1 in OS patients were associated with clinical stage, distant metastasis and unfavorable survivals. A multivariate Cox model revealed that ZEB2-AS1 expression was an independent prognostic factor for OS patients. Cellular experiments revealed that knockdown of ZEB2-AS1 inhibited proliferation and metastasis, and induced apoptosis in vitro. Mechanistic investigation revealed that ZEB2-AS1 acted as a sponge for miR-107 and blocked the inhibition of spalt like transcription factor 4 (SALL4) via miR-107 in OS cells. Rescue experiments suggested that up-regulation of ZEB2-AS1 could partly attenuate the miR-107 mediated inhibition of SALL4 expression in OS cells. To sum up, our data revealed that ZEB2-AS1 played an oncogenic role in OS progression, and could serve as a novel molecular target for treating this tumor.Recent studies have shown the involvement of exosomes in intercellular communication during tumor progression. Circular RNAs (circRNAs) can be packaged into exosomes for extracellular communication, however, the possible effects of exosomal circRNAs in epithelial ovarian cancer (EOC) cells with high metastatic potential have been rarely studied. In this study, we identified exosomal circRNA051239 from high-metastatic ovarian cancer SKOV3.ip cells and subsequently analyzed circRNA051239 levels in both EOC tissues and exosomes derived from plasma and cells by qRT-PCR. A variety of in vitro assays were employed to observe the effects of exosomal circRNA051239 derived from high-metastatic ovarian cancer SKOV3.ip cells on low-metastatic ovarian cancer SKOV3 cells. Bioinformatics analysis and luciferase activity assays were further utilized to confirm the relationship between circRNA051239, miR-509-5p and PRSS3. As a result, circRNA051239 expression was increased in tissues and plasma exosomes from EOC patients. Moreover, si-circRNA051239-Exo (exosomes derived from circRNA051239 knockdown SKOV3.ip cells) inhibited the proliferation, migration as well as invasion of SKOV3 cells. Mechanistically, circRNA051239 functioned as a competitive endogenous RNA (ceRNA) by sponging miR-509-5p to facilitate PRSS3 expression. Exosomal circRNA051239 derived from high-metastatic ovarian cancer SKOV3.ip cells promoted the progression of low-metastatic ovarian cancer SKOV3 cells. Collectively, these outcomes implicated that higher metastatic EOC cells can confer this potential to lower metastatic potential via exosomal circRNA051239, causing enhanced proliferative, migratory and invasive capacities in recipient cells.