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.

Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins.

BACKGROUND: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. METHODS: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. RESULTS: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. CONCLUSIONS: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses.

Seroprevalence and associated risk factors of Toxoplasma gondii among Manchu pregnant women in northeastern China.

Toxoplasma gondii is an intracellular protozoan parasite infecting human and almost all warm-blooded animals. It may cause several severe symptoms if pregnant women infection with T. gondii, including misbirth. A cross-sectional study was conducted containing 313 Manchu pregnant women attending antenatal care from 2016 to 2017 in Jilin province, northeastern China, and were assessed by enzyme-link immunosorbent assay and the study utilized univariate analysis to identify the potential risk factors for T. gondii infection. Of the 313 investigated Manchu pregnant women, 51 (16.29%, 95% CI 12.2-20.4) were tested as T. gondii-seropositive, with 47 (15.02%) seropositive for T. gondii IgG antibodies and 8 (2.56%) IgM positive. The seroprevalence of T. gondii in different age groups varied from 13.50% (8.7-18.3) to 23.90% (13.9-41.9). Pregnant raising cat at home has a significantly higher seroprevalence of T. gondii than no cat at home. Pregnant consuming raw/undercooked meat has a significantly higher T. gondii seroprevalence than individuals did not consuming raw/undercooked meat. This is the first study of T. gondii infection seroprevalence in Manchu pregnant women. Risk factors analysis suggested that seroprevalence of T. gondii in investigated Manchu pregnant women was mainly related to consumption of raw/undercooked meat and raising cat at home. The findings will provide key and baseline data for prevention and control of toxoplasmosis among Manchu pregnant women and other people.

Effect of fertilizer and water content on N2O emission from three plantation soils in south China.

The effects of fertilizers and water content on N2O emission were studied using the three most typical plantation soils. Soil incubations were performed and fertilization and water content treatments were designed. At 25% of saturated water content(SWC), N2O emissions from the soil treated with urea, KNO3, (NH4)2 SO4 and KH2 PO4 were compared at application rates of 0, 100, 200, 300 and 500 kg/hm2. At 80% of SWC, similar experiments were carried out but at only one application rate(500 kg/hm2). N2O emissions at various water contents(20%, 35%, 50%, 65%, 80% and 100% of SWC) were studied. At low water content(25% of SWC), neither nitrogen nor phosphorus(or potassium) fertilizers led to a high level of N2O emission, which generally ranged from 2.03 to 29.02 microg/(m2 x h). However, at high water content(80% SWC), the fertilizers resulted in much greater N2O emission irregardless of soil tested. The highest N2O emission rates after 24 h of water addition were 1233 microg/(m2 x h) for S. superba soil, 1507 microg/(m2 x h) for P. elliottii soil and 1869 microg/ (m2 x h) for A. mangium soil respectively. N2O emission from soils treated with urea, (NH4)2 SO4 and KH2 PO4 immediately dropped to a low level but steadily increased to a very high level for the soil treated with KNO3. High NO3- content was a basis of high level of N2O emission. N2O emission rates from soils peaked shortly after flooding, rapidly dropping to a very low level in soil from non-legume plantations, but lasting for a relatively long period in soil from legume plantations. When soil water content increased equaling to or higher than 65%, the accumulated N2O emission over a period of 13 d ranged from 20.21-29.78 mg/m2 for S. superba, 30.57-70.12 mg/m2 for P. elliottii and 300.89-430.51 mg/m2 for A. mangium. The critical water content was 50% of SWC, above which a high level of N2O emission could be expected, and below which very little N2O emissions were detected. The results suggest that, at low water content (< 50% of SWC), the fertilization practice is safe with regard to N2O emissions, but at high water content (> 50% of SWC), nitrogen fertilizer in the form of nitrate could yield a 100-fold increase in N2O emissions. Legume plantations like A. mangium should be avoided in low lands which could easily suffer from flooding or poor drainage.