The development and role of microbialhost interactions in gut mucosal immune development

At birth the piglet＇s immune system is immature and it is dependent upon passive maternal protection until weaning.The piglet＇s mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet＇s intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond ＂appropriately＂ to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.

Stochastic responses of tumor-immune system with periodic treatment

We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito＇s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools.

Identification of senescence-related molecular subtypes and key genes for prostate cancer

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer(PCa)patients undergoing radical prostatectomy(RP)or radical radiotherapy(RT).We conducted all analyses using R software and its suitable packages.Twelve genes,namely,secreted frizzled-related protein 4(SFRP4),DNA topoisomerase II alpha(TOP2A),pleiotrophin(PTN),family with sequence similarity 107 member A(FAM107A),C-X-C motif chemokine ligand 14(CXCL14),prostate androgen-regulated mucin-like protein 1(PARM1),leucine zipper protein 2(LUZP2),cluster of differentiation 38(CD38),cartilage oligomeric matrix protein(COMP),vestigial-like family member 3(VGLL3),apolipoprotein E(APOE),and aldehyde dehydrogenase 2 family member(ALDH2),were eventually used to subtype PCa patients from The Cancer Genome Atlas(TCGA)database and GSE116918,and the molecular subtypes showed good correlations with clinical features.In terms of the tumor immune environment(TME)analysis,compared with cluster 1,cancer-associated fibroblasts(CAFs)scored significantly higher,while endothelial cells scored lower in cluster 2 in TCGA database.There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence(BCR)-free survival for PCa patients undergoing RP.For the GSE116918 database,cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal,immune,and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data(ESTIMATE)scores than cluster 1;in addition,patients with high levels of CAFs,stromal scores,immune scores,and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR.Based on the median of differentially expressed checkpoints,high expression of CD96,hepatitis A virus cellular receptor 2(HAVCR2),and neuropilin 1(NRP1)in GSE116918 and high expression of CD160 and tumor necrosis factor(ligand)superfamily member 18(TNFSF18)in TCGA database were associated with a significantly higher risk of BCR than their counterparts.In conclusion,we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

Epididymitis： revelations at the convergence of clinical and basic sciences

Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.