Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. METHODS: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. RESULTS: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. CONCLUSION: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.

Fatal, non-fatal burden of cancer in the elderly in China, 2005-2016: a nationwide registry-based study.

BACKGROUND: As populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control. METHODS: Data on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008-2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model. RESULTS: From 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84-1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60-64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10-1.82%). Female breast cancer was one of the top five cancers in the 60-64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35-3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose. CONCLUSIONS: From 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.

Trends of cancer incidence among Chinese older adults from 2005 to 2016: A log-linear regression and age-period-cohort analysis.

Background: To study the corresponding strategies for controlling cancer in older adults aged 60 and above in China, a comprehensive assessment of disease burden is required. Therefore, we will introduce the cancer epidemiological characteristics of older adults in China over a recent 12 year period. Methods: The age-period-cohort model was constructed using the cancer incidence data from the Chinese Cancer Registry Annual Report published in 2008-2019. The annual change percentage (APC) was estimated by log-linear regression to reflect the time trend. The data from the GLOBOCAN 2020 database was selected for worldwide comparative analysis. Results: The cancer incidence in older adults aged 60 and above in China showed a decreasing trend (APC = -0.73%, P = 0.009). The urban/rural ratio of cancer incidence increased from 0.94 to 1.07 (t = 3.52, P < 0.05), while the sex ratio (male/female) showed a significant decreasing trend only in rural areas (t = -6.77, P < 0.05), and the ratio decreased from 2.02 to 1.72. The results of the age-period-cohort model showed that the cancer incidence increased with age in both males and females, urban and rural areas. The RR of period effect increased from 2005 to 2010, then decreased from 2010 to 2015, and the downward trend was more obvious. The RR of the later-born cohort was lower than that of the earlier-born cohort in rural areas. Lung, gastric, colorectal, esophageal, liver, and breast cancers were common cancers in Chinese older adults. Lung cancer incidence ranked first in males, and it decreased with time in the 75-79 and 80-84 age groups (APC75 - 79 = -1.10%, APC80 - 84 = -0.88%, all P < 0.05). Breast cancer incidence ranked first among female in the 60-64 age group and showed an increasing trend (APC60 - 64 = 1.52%, P < 0.05). Conclusions: The cancer incidence in Chinese older adults aged 60 and above showed a decreasing trend, but it was still at a relatively high level. The key targets of prevention and treatment should be males, urban areas, younger people, older adults aged 60-69, lung, gastrointestinal, and breast cancers in the future.

Exposure time determines the protective effect of Trichinella spiralis on experimental colitis.

Several studies demonstrate the protective effect of Trichinella spiralis (T. spiralis) on autoimmune diseases, however the optimal exposure time remains unexplored. This study aimed to determine whether pre-exposure of mice to T. spiralis conferred greater protection than introduction of the parasite in the acute phase of experimental colitis. We compared the effect of T. spiralis on dextran sodium sulfate (DSS)-induced colitis using two exposure paradigms: introduction three weeks prior to, or immediately after the induction period. Inflammation scores, morphological changes and cytokine profiles in serum and colonic tissue were assessed. At a parasite dose of 300 cysts, post exposure had a more pronounced effect on cytokine profiles, improved gross appearance of colon tissue, and reduced inflammatory symptoms. In addition, we demonstrate that regardless of cyst number, pre-exposure to T. spiralis did not confer protective benefits when compared to parasite introduction in the acute phase of DSS-induced colitis. Moreover, our data indicates that the underlying mechanisms of action involve an IL-17/TNF-alpha synergistic reaction, suppression of Th1 and Th2 responses, and an upregulation of the regulatory cytokines IL-10 and TGF-beta 1. Our results demonstrate that moderate exposure to T. spiralis in the acute phase of DSS-induced colitis improves disease associated inflammation and tissue disruption.

Bioinformatics of excretory/secretory proteins of Toxoplasma gondii strain ME49.

Toxoplasma gondii is an obligate intracellular parasite that is globally distributed and can infect almost all warm-blooded animals, including humans. While vaccines are not available for prophylaxis, there are limited therapeutic options which often do not result in eradication of parasites from patients. ME49 is a cystogenic strain of T. gondii with a potential as a vaccine candidate. Excretory and secretory (ES) proteins are thought to play crucial roles in host-parasite interactions. Hence, we predicted and functionally annotated the ES proteins in T. gondii ME49 using public databases. ES proteins were further examined for the characteristics and possible functions through gene ontology (GO) term enrichment and analyses of metabolic pathways, enzyme code distribution (EC distributing) and protein domains. The potential antigenicity of T. gondii ME49 ES proteins was evaluated for the first time using Abundance of Antigenic Regions (AAR) value to predict the antigenic potential by measuring sequence length and number of antigenic regions. The results showed that the ES proteins have different AAR values at RNA and microarray level. Our studies provide valuable information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnostic and immunoprophylactic interests.