Fungi and tumors: The role of fungi in tumorigenesis (Review).

Fungi inhabit different anatomic sites in the human body. Advances in omics analyses of host­microbiome interactions have tremendously improved our understanding of the effects of fungi on human health and diseases such as tumors. Due to the significant enrichment of specific fungi in patients with malignant tumors, the associations between fungi and human cancer have attracted an increasing attention in recent years. Indeed, cancer type­specific fungal profiles have been found in different tumor tissues. Importantly, fungi also influence tumorigenesis through multiple factors, such as host immunity and bioactive metabolites. Microbiome interactions, host factors and fungal genetic and epigenetic factors could be involved in fungal enrichment in tumor tissues and/or in the conversion from a commensal fungus to a pathogenic fungus. Exploration of the interactions of fungi with the bacterial microbiome and the host may enable them to be a target for cancer diagnosis and treatment. In the present review, the associations between fungi and human cancer, cancer type­specific fungal profiles and the mechanisms by which fungi cause tumorigenesis were discussed. In addition, possible factors that can lead to the enrichment of fungi in tumor tissues and/or the conversion of commensal fungi to pathogenic fungi, as well as potential therapeutic and preventive strategies for tumors based on intratumoral fungi were summarized.

Gut fungal mycobiome: A significant factor of tumor occurrence and development.

A variety of bacteria, viruses, fungi, protists, archaea and protozoa coexists within the mammalian gastrointestinal (GI) tract such as that fungi are detectable in all intestinal and colon segments in almost all healthy adults. Although fungi can cause infectious diseases, they are also related to gut and systemic homeostasis. Importantly, through transformation of different forms such as from yeast to hyphae, interaction among gut microbiota such as fungal and bacterial interaction, host factors such as immune and host derived factors, and fungus genetic and epigenetic factors, fungi can be transformed from commensal into pathogenic lifestyles. Recent studies have shown that fungi play a significant role in the occurrence and development of tumors such as colorectal cancer. Indeed, evidences have shown that multiple species of different fungi exist in different tumors. Studies have also demonstrated that fungi are related to the occurrence and development of tumors, and also survival of patients. Here we summarize recent advances in the transformation of fungi from commensal into pathogenic lifestyles, and the effects of gut pathogenic fungi on the occurrence and development of tumors such as colorectal and pancreatic cancers.

Outcome of a novel porcine-derived UBM/SIS composite biological mesh in a rabbit vaginal defect model.

INTRODUCTION AND HYPOTHESIS: To investigate the tissue reactions of a novel porcine-derived urinary bladder matrix/small intestinal submucosa (UBM/SIS) biological mesh and SIS mesh implanted in a rabbit vaginal defect model. METHODS: Thirty-two rabbits were implanted with UBM/SIS mesh (Group A) and SIS mesh (Group B), respectively. Rabbits were sacrificed at 7, 14, 60, and 180 days after implantation. The tensile strength, elongation at break, and elastic modulus of the tissue were measured using biomechanical methods. The inflammatory response, cell infiltration, vascularization, and collagen fibers were observed. RESULTS: Compared with Group B, the tensile strength and elongation at break of group A was higher at 14, 60, and 180 days. The elastic modulus of group A was lower at 180 days. Inflammatory response of group A was milder at 14, 60, and 180 days. There was more cell infiltration in group A at 7 and 14 days. Vascularization was higher in group A at 7 days and 14 days. The order of collagen in group A was better at 14, 60, and 180 days. The proportion of thick red fibers in both groups showed an increasing trend. At 14 days, group A had more thick red fibers. CONCLUSIONS: The novel UBM/SIS composite mesh had a milder inflammatory response; earlier induction of cell infiltration, angiogenesis, and collagen regeneration. Collagen fibers had a better order. It has a higher tensile strength and greater elongation at break, and can be used as a potential material for the treatment of pelvic organ prolapse.

Effects of particle size and binding affinity for small interfering RNA on the cellular processing, intestinal permeation and anti-inflammatory efficacy of polymeric nanoparticles.

BACKGROUND: Silencing of excessive secreted tumour necrosis factor (TNF)-α from macrophages might be an effective therapy of ulcerative colitis (UC), which acquires improvements on small interfering RNA (siRNA) delivery vectors. Thus, in the present study, the effects of particle size and binding affinity of four polymeric nanoparticles on siRNA delivery for the treatment of UC were evaluated. METHODS: Galactosylated trimethyl chitosan-cysteine (GTC) nanoparticles of varying particle size and binding affinity for siRNA were prepared and TNF-α siRNA was encapsulated. Their cellular transport was investigated in murine macrophages and Caco-2 cell monolayers were utilized to analysis the intestinal permeation. Finally, in vivo anti-inflammatory efficacy was assessed in a mouse model of UC. RESULTS: Although marginal effects of particle size on the in vitro gene silencing efficiency were detected, GTC nanoparticles with a particle size of 450 nm and stronger binding affinity for siRNA showed reduced intestinal epithelial permeability and enhanced in vivo anti-inflammatory efficacy compared to those with a particle size of 200 nm. By contrast, the delivery processes were significantly affected by the binding affinity for siRNA, where smaller GTC nanoparticles (200 nm) with moderate siRNA binding strength exhibited remarkable cytoplasmic distribution and sufficient intracellular release of siRNA, as well as a sustained in vitro and in vivo gene silencing effect. CONCLUSIONS: Nanoparticles with a particle size of 450 nm or balanced binding affinity for siRNA might be preferable for the treatment of ulcerative colitis.