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A previous study described a novel serine protease inhibitor 16 from Musca domestica (MDSPI16), which inhibited the elastase and chymotrypsin. It also exhibited a potential anti-inflammatory activity for acute lung injury (ALI), while its effects on ALI are yet to be elucidated. The present study aimed to investigate the effects and the underlying mechanisms of MDSPI16 on lipopolysaccharide (LPS)-challenged mice and bone marrow neutrophils. The ALI model based on the results of LPS-induced mice demonstrated that MDSPI16 markedly reduced the infiltration of inflammatory cells, protein exudation in lung tissues, and downregulated the level of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the LPS-stimulated mouse bone marrow neutrophils model was employed to determine the role of MDSPI16. The cytokine levels were quantified by both the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Consequently, the expression of IL-6, IL-1β, and TNF-α was found to be inhibited by MDSPI16 in a dose-dependent manner. Moreover, MDSPI16 also inhibited the mouse neutrophils nuclear factor-κB (NF-κB) signaling pathway, c-Jun N-terminal kinase (JNK) signaling pathway, ERK1/2 and AP-1 signaling pathway in addition to the expression of iNOS and COX-2 proteins, which in turn, might alleviate the release of pro-inflammatory cytokines during ALI. Therefore, MDSPI16 could be proposed as a potential and novel drug therapy for ALI.Epidemiological and basic research has suggested that Helicobacter pylori (H. pylori, Hp) infection has a protective function in inflammatory bowel disease (IBD); however, the mechanisms are not very clear. Here, we investigated the role of exosomes derived from Hp-infected patients in IBD. Human intestinal epithelial cells were treated with serum exosomes derived from Hp-positive chronic gastritis patients (Exo(Hp)), the expression of cytokines, inflammasome and signal pathway genes were detected by antibody microarray or PCR array. Furthermore, DSS-induced colitis mice were treated with exosomes by intraperitoneally injection. The results demonstrated that Exo(Hp) promoted NLRP12 expression in intestinal epithelial cells, and NLRP12 decreased chemokine MCP-1 and MIP-1α expression by inhibiting the Notch signaling pathway. N-butyl-N-(4-hydroxybutyl) nitrosamine datasheet Next, in vivo, results showed that Exo(Hp) attenuated the inflammatory responses in DSS-induced colitis mice and improved colitis symptoms, outcomes associated with an increase in NLRP12 expression. Furthermore, the immunohistochemistry results showed that NLRP12 was negatively correlated with the disease activity of pediatric IBD patients. These results provide new theoretical bases for further elucidation of the protective mechanisms of Hp infection in IBD, and suggest new targets for explorations of effective interventional strategies for IBD.Cancer vaccines are usually derived from the patient's tumor cells or the antigens found on their surface, which may help the immune system to identify and kill these malignant cells. Current focus of many researches is designing vaccines with the hope of triggering the immune system to attack cancer cells in a more effective, reliable and safe manner. Although colorectal cancer (CRC) is recognized as the third leading cause of death by cancer, but significant advances in therapy strategies have been made in recent years, including cancer vaccine. In this review, we present various vaccine platforms that have been used in the border battle against CRC, some of which have been approved for clinical use and some are in late-stage clinical trials. Until September 2020 there is approximately 1940 clinical trials of cancer vaccines on patients with different cancer types, and also many more trials are in the planning stages, which makes it the most important period of therapeutic cancer vaccines studies in the history of the immunotherapy. In cancer vaccines clinical trials, there are several considerations that must be taken into account including engineering of antigen-presenting cells, potential toxicity of antigenic areas, pharmacokinetics and pharmacodynamics of vaccines, and monitoring of the patients' immune response. Therefore, the need to overcome immunosuppression mechanisms/immune tolerance is a critical step for the success of introducing therapeutic vaccines into the widely used drugs on market. In this way, better understanding of neoantigens, tumor immune surveillance escape mechanisms and host-tumor interactions are required to develop more effective and safe cancer vaccines.

The clinical impact of sarcopenia on the immune checkpoint inhibitor's (ICI) efficacy and immune-related adverse events in non-small cell lung cancer (NSCLC) patients is unclear. Therefore, the purpose of this study is to evaluate the association between sarcopenia and clinical outcomes of ICI immunotherapy.

A systematic literature search of PubMed, Embase, Cochrane CENTRAL, and conference databases was conducted for the relevant studies. The primary outcomes were progression-free survival (PFS) and overall survival (OS) measured by hazard ratio (HR) with 95% confidence interval (CI), and the secondary outcomes were disease control rate, overall response rate, and immune-related adverse events measured by relative risk (RR) with 95% CI. Subgroup and sensitivity analysis were performed.

Pre-immunotherapy sarcopenia was significantly associated with worse OS (HR = 1.61, 95% CI = 1.24-2.10) and PFS (HR = 1.98, 95% CI = 1.32-2.97). Development or worsening of sarcopenia during immunotherapy also predicted worse OS and PFS. Both pre-immunotherapy sarcopenia (RR = 0.70, 95% CI = 0.56-0.86) and development or worsening of sarcopenia (RR = 0.62, 95% CI = 0.40-0.96) resulted in a lower disease control rate. Sarcopenia tended toward a lower overall response rate, although there was no significant difference (RR = 0.54, 95% CI = 0.19-1.53). Moreover, sarcopenia did not increase immune-related adverse events (RR = 0.99, 95% CI = 0.21-4.67).

Sarcopenia was associated with worse treatment response and shorter long-term efficacy in NSCLC patients treated with ICI immunotherapy. Moreover, sarcopenia does not increase the rate of immune-related adverse events.

Sarcopenia was associated with worse treatment response and shorter long-term efficacy in NSCLC patients treated with ICI immunotherapy. Moreover, sarcopenia does not increase the rate of immune-related adverse events.