Cyanobacterial blooms triggered by eutrophication and climate change have become a global public health issue. The toxic metabolites microcystins (MCs) generated by cyanobacteria can accumulate in food chain and contaminate water, thus posing a potential threat to human and animals health. Studies have suggested that aside liver, the kidney may be another target organ of MCs intoxication. Therefore, this review provides various evidences on the nephrotoxicity of MCs. The review concludes that nephrotoxicity of MCs may be related to inhibition of protein phosphatases and excessive production of reactive oxygen species, cytoskeleton disruption, endoplasmic reticulum stress, DNA damage and cell apoptosis. To protect human from MCs toxic consequences, this paper also puts forward some directions for further research.

Introduction: Inflammatory bowel disease (IBD) is a chronic disease involving multiple genes, and the current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. MiR-146a plays a pivotal role in repression of innate immunity, but its function in the intestinal inflammation is sort of controversy, and the genetic regulatory networks regulated by miR-146a in IBD has not been revealed.Methods: RT-qPCR was employed to detect the expression of miR-146a in IBD patients and in a mouse IBD model induced by dextran sulfate sodium (DSS), and then we generated a miR-146a knock-out mouse line with C57/Bl6N background. The disease activity index was scored in DSS-treated miR-146a deficiency mice and their wild type (WT) littermates. Bulk RNA-sequencing, RT-qPCR and immunostaining were done to illustrate the downstream genetic regulatory networks of miR-146a in flamed colon. Finally, the modified miR-146a mimics were used to treat DSS-induced IBD in miR-146a knock-out and WT IBD mice.Results: We showed that the expression of miR-146a in the colon was elevated in dextran sulfate sodium (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and more significant rectal bleeding, shorter colon length, and colitis in miR-146a knock-out mice than WT mice. The miR-146a mimics alleviated DSS-induced symptoms in both miR-146a^-/- and WT mice. Further RNA sequencing illustrated that the deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes that cover multiple genetic regulatory networks in IBD, and supplementation with miR-146a mimics inhibited the expression of many IBD-related genes. Quantitative RT-PCR or immunostaining confirmed that Ccl3, Saa3, Csf3, Lcn2, Serpine1, Serpine2, MMP3, MMP8, MMP10, IL1A, IL1B, IL6, CXCL2, CXCL3, S100A8, S100A9, TRAF6, P65, p-P65, and IRAK1 were regulated by miR-146a in DSS induced IBD. Among them, MMP3, MMP10, IL6, IL1B, S100A8, S100A9, SERPINE1, CSF3, and IL1A were involved in the active stage of IBD in humans.Discussion: Our date demonstrated that miR-146a acts as a top regulator in C57/BL6N mice to systematically repress multiple genetic regulatory networks involved in immune response of intestine to environment factors, and combinatory treatment with miR-146a-5p and miR-146a-3p mimics attenuates DSS-induced IBD in mice through down-regulating multiple genetic regulatory networks which were increased in colon tissue from IBD patients. Our findings suggests that miR-146a is a top inhibitor of IBD, and that miR-146a-5p and miR-146a-3p mimics might be potential drug for IBD.

Background.: Our aim was to document the relationship between clinical and MRI evidence of trigeminal nerve involvement.Methods.: The MRI and medical records of 924 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were reviewed retrospectively.Results.: A total of 92 divisions of palsied trigeminal nerves were found clinically in 46 patients (5.0%). The involved trigeminal nerve was ophthalmic nerve (V1; n = 21), the maxillary division (V2; n = 41), and the mandibular division (V3; n = 30). Of the 316 patients with MRI‐demonstrated trigeminal nerve involvements, the symptoms were lacking in 270 patients (85.4%). Of the 92 clinical palsied trigeminal nerve divisions, 91 nerves (98.9%) showed MRI evidence of 1 or more trigeminal nerve involvements. Of the 91 palsied trigeminal nerve with MRI evidence, 85 divisions (93.4%) were found with intracranial or orbital segment involvement, 6 (6.6%) divisions were found only basicranial evidence, and 83 (91.2%) divisions were found with cavernous sinus invasion.Conclusion.: The incidence of MRI‐evidenced trigeminal nerve involvement is high and often asymptomatic in NPC. Almost all patients with clinical trigeminal nerve palsies had MRI evidence of trigeminal nerve involvement in intracranial or orbital segment, especially in cavernous sinus. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Background and aims: Bacteroides fragilis toxin (BFT), produced by enterotoxigenic B. fragilis (ETBF), is crucial for ETBF-induced colitis. This study aims to investigate the impact of BFT–host interactions on N6-methyladenosine (m6A) modification of host mRNA and its underlying mechanisms. Methods: Single-cell sequencing was employed to identify the cell types involved in ETBF-induced colitis in inflammatory bowel disease patients and dextran sodium sulfate-induced colitis mice. An ETBF strain with the bft gene deleted (ETBF[Δbft]) was utilized to investigate the role of ETBF components. The biological functions and mechanisms of BFT-induced m6A modifications, as well as the target genes, were explored in vitro and in vivo. Results: Inflammatory macrophages are enriched in the intestinal mucosal tissue of both inflammatory bowel disease patients and mice with high levels of ETBF. Additionally, ETBF triggers the activation of inflammatory macrophages, subsequently inducing downstream inflammatory responses. Remarkably, BFT secreted by ETBF reduced METTL3 transcription by inhibiting FOXD3 expression and induced a dramatic reduction of m6A modifications in inflammatory macrophages. Moreover, BFT promotes the expression of its target ITGA5 expression by diminishing YTHDF2-dependent mRNA degradation. Targeting integrin subunit alpha 5 using Cilengitide significantly alleviated ETBF-induced colitis by decreasing the level of inflammatory factors in macrophages. Conclusions: Our study reveals that BFT produced by ETBF leads to a reduction of m6A modifications by reducing METTL3 transcription and promotes ITGA5 expression in inflammatory macrophages. These findings provide new insights into the modulation of human m6A epitranscriptome in macrophages by gut microbiota and its significance in inflammatory bowel disease progression.

Inflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even IBD. To explore MC-LR’s effects and potential mechanisms on IBD occurrence and development, we used dextran-sulfate sodium gavage (DSS) and MC-LR together for the first time in mice. There were four groups of mice: (A) mice given PBS gavage (control, CT); (B) mice given 3% DSS gavage (DSS); (C) mice given 200 µg/kg MC-LR gavage (MC-LR); and (D) mice given 3% DSS + 200 µg/kg MC-LR gavage (DSS + MC-LR). Compared with the CT group, the MC-LR group and the DSS group demonstrated more severe colitis results, which presented as higher weight loss, an increased Disease Activity Index (DAI) score, shorter colon length, a higher degree of tissue structural damage, more apoptotic cells, and greater pro-inflammatory cytokines. Similarly, the DSS + MC-LR group showed more severe colitis compared with the DSS group. Subsequent experiments confirmed that MC-LR or DSS increased the expression of pyroptosis-related proteins mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3). Likewise, compared with the DSS group, the DSS + MC-LR group expressed these proteins at a higher level. In conclusion, our research is the first to show that MC-LR may induce colitis, and even IBD, through NLRP3 inflammasome-mediated pyroptosis, and it could aggravate DSS-induced colitis in the same way.