Endoplasmic reticulum stress-mediated cell death in cardiovascular disease.

The endoplasmic reticulum (ER) plays a vital function in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) can trigger various modes of cell death by activating the unfolded protein response (UPR) signaling pathway. Cell death plays a crucial role in the occurrence and development of diseases such as cancer, liver diseases, neurological diseases, and cardiovascular diseases. Several cardiovascular diseases including hypertension, atherosclerosis, and heart failure are associated with ER stress. ER stress-mediated cell death is of interest in cardiovascular disease. Moreover, an increasing body of evidence supports the potential of modulating ERS for treating cardiovascular disease. This paper provides a comprehensive review of the UPR signaling pathway, the mechanisms that induce cell death, and the modes of cell death in cardiovascular diseases. Additionally, we discuss the mechanisms of ERS and UPR in common cardiovascular diseases, along with potential therapeutic strategies.

A novel Bursin-like peptide as a potential virus inhibitor and immunity regulator in SPF chickens infected with recombinant ALV.

BACKGROUND: Avian leukosis viruses (ALVs) are important contagious suppressive factors of chicken immunity and growth performance, resulted in enormous economic loss. Although virus eradication programs are applied in breeder flocks, ALVs are still widespread globally. Therefore, other valuable adjunct to reduce the negative effect of ALVs should be considered. Bursin-like peptide (BLP) showed remarkable immunomodulatory effects, whereas their influence on ALV-infected avian groups has not been reported. Here, a designed hybrid BLP was expressed in E. coli. The purified BLP was injected subcutaneously weekly in SPF chickens congenitally infected with a natural ALV strain. Then the influences of this BLP on the growth performance, immune response and virus titer of ALV-infected chickens were determined. RESULTS: This BLP injection significantly improved the body weights of ALV-infected birds (P < 0.05). BLP injection significantly enhanced organ index in the BF in ALV-infected birds (P < 0.05). The weekly injection of BLP significantly lengthened the maintenance time of antibodies against Newcastle disease virus (NDV) attenuated vaccine of ALV-infected birds (P < 0.05) and boosted the antibody titer against avian influenza virus (AIV) H5 inactive vaccine of mock chicken (P < 0.05). BLP injection in mock chickens enhanced the levels of serum cytokines (IL-2, IL-4 and interferon-γ) (P < 0.05). Surprisingly, the novel BLP significantly inhibited expression of the ALV gp85 gene in the thymus (P < 0.05), kidney (P < 0.05) and bursa of Fabricius (BF) (P < 0.01) of ALV-infected chickens. Both viral RNA copy number and protein level decreased significantly with BLP (50 µg/mL) inoculation before ALV infection in DF1 cells (P < 0.05). CONCLUSIONS: This is the first report investigating the influence of BLP on the growth and immunity performance of chickens infected by ALV. It also is the first report about the antiviral effect of BLP in vivo and in vitro. This BLP expressed in E. coli showed potential as a vaccine adjuvant, growth regulator and antiretroviral drug in chickens to decrease the negative effects of ALV infection.

Evidence of Astragalus injection combined platinum-based chemotherapy in advanced nonsmall cell lung cancer patients: A systematic review and meta-analysis.

BACKGROUND: Platinum-based chemotherapy is one of the standard treatments for advanced nonsmall cell lung cancer (NSCLC). Despite on an effective treatment for advanced NSCLC patients, its high toxicity and limited clinical effects have raised big concerns. Astragalus injection (AGI) has been commonly employed as an adjutant chemotherapy drug for NSCLC in China. This review was conducted to evaluate the beneficial of AGI in combination with platinum-based chemotherapy in advanced NSCLC. METHODS: We collected all studies about AGI plus platinum-based chemotherapy for advanced NSCLC in the PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, China Biological Medicine Database, and Chinese Scientific Journal Database established on July 2018 without language restriction. Cochrane handbook was applied to assess the quality of included trials. Stata (version 12.0) and RevMan (version 5.3) were employed for data analysis. The quality of the evidence was assessed with the GRADE approach. RESULTS: Nineteen randomized controlled trials (RCTs) including 1635 patients were included to determine the effectiveness and safety of AGI combined with platinum-based chemotherapy in the treatment of NSCLC. The result of meta-analysis indicated that comparing with chemotherapy alone, AGI combined chemotherapy could significantly improve the objective response rate (relative risk [RR] = 1.19, 95% confidence interval [CI] [1.06, 1.33], P = .002), the Karnofsky performance status (RR = 2.28, 95% CI [1.63, 3.18], P < .00001), and 1-year survival rate (RR = 1.40, 95% CI [1.16, 1.70], P = .0005), meanwhile increase the percentages of CD3 (weighted mean differences [WMD] = 11.98, 95% CI [8.0, 15.96], P < .00001), CD4 (WMD = 2.98, 95% CI [0.45, 5.52], P = .02), CD4/CD8 (WMD = 0.33, 95% CI [0.20, 0.46], P < .00001), and NK cells (WMD = 9.5, 95% CI [7.25, 11.76], P < .00001), decrease the incidence of leukopenia (RR = 0.52, 95% CI [0.44, 0.61], P < .00001), platelet toxicity (RR = 0.62, 95% CI [0.50, 0.76], P < .00001), and vomiting (RR = 0.72, 95% CI [0.60, 0.87], P = .0006). Based on the system evaluation results, the GRADE system recommendation grading method was adopted to evaluate the evidence quality. The results showed that the level of evidence was low. CONCLUSIONS: The AGI apparently has attenuation and synergistic efficacy to platinum-based chemotherapy patients. However, considering the limits of articles included in the present researches, the recommendation is likely to be weak. High-quality RCTs are urgently used to generate conclusive results.

Transcription analysis of the interaction between chicken thymus and recombinant avian leukosis virus isolate FJ15HT0.

Avian leukosis virus (ALV) induces multiple avian tumors, growth decrease and immune suppression. Previously, a novel natural recombinant ALV isolate FJ15HT0 was proven to be associated with significant body weight decrease, immune suppression and lymphocytoma in infected SPF chickens. In order to uncover the interaction between virus and host, we compared differences in the transcriptomes of the thymuses from the mock chickens and simulated congenitally infected chickens at 5days (d), 13d and 21d of age by RNA-seq analysis of the thymuses. Signaling pathways including cytokine-cytokine receptor interactions, peroxisome proliferator-activated receptor (PPAR) signaling pathway, Janus tyrosine kinase/signal transducers and activators of transcription (Jak-STAT) signaling pathway and fatty acid degradation were involved in the interaction between FJ15HT0 and SPF chickens. Interestingly, fold change of ciliary neurotrophic factor receptor α (CNTFRα) in infected donor collected from 2d to 21d showed a significant positive correlation with the corresponding expression of the viral gp85 gene in thymuses (r=0.656, P<0.01) and in livers (r=0.525, P<0.05). It will provide new insights for the molecular pathogenesis of ALV infection.