Huanglohmann1997

In the mouse model, this signature with the murine homologs of the corresponding proteins was also identified. A2MG, MMP-7, and A1AT serve as biomarkers in patients with CDI and define novel components of the host response that may determine disease severity.Kir5.1 is an inwardly rectifying potassium (Kir) channel subunit abundantly expressed in the kidney and brain. We previously established the physiologic consequences of a Kcnj16 (gene encoding Kir5.1) knockout in the Dahl salt-sensitive rat (SSKcnj16-/-), which caused electrolyte/pH dysregulation and high-salt diet-induced mortality. Dapagliflozin price Since Kir channel gene mutations may alter neuronal excitability and are linked to human seizure disorders, we hypothesized that SSKcnj16-/- rats would exhibit neurological phenotypes, including increased susceptibility to seizures. SSKcnj16-/- rats exhibited increased light sensitivity (fMRI) and reproducible sound-induced tonic-clonic audiogenic seizures confirmed by electroencephalography. Repeated seizure induction altered behavior, exacerbated hypokalemia, and led to approximately 38% mortality in male SSKcnj16-/- rats. Dietary potassium supplementation did not prevent audiogenic seizures but mitigated hypokalemia and prevented mortality induced by repeated seizures. These results reveal a distinct, nonredundant role for Kir5.1 channels in the brain, introduce a rat model of audiogenic seizures, and suggest that yet-to-be identified mutations in Kcnj16 may cause or contribute to seizure disorders.Glioblastoma multiforme (GBM) is a fatal human cancer in part because GBM stem cells are resistant to therapy and recurrence is inevitable. Previously, we demonstrated Zika virus (ZIKV) targets GBM stem cells and prevents death of mice with gliomas. Here, we evaluated the immunological basis of ZIKV-mediated protection against GBM. Introduction of ZIKV into the brain tumor increased recruitment of CD8+ T and myeloid cells to the tumor microenvironment. CD8+ T cells were required for ZIKV-dependent tumor clearance because survival benefits were lost with CD8+ T cell depletion. Moreover, while anti-PD-1 antibody monotherapy moderately improved tumor survival, when coadministered with ZIKV, survival increased. ZIKV-mediated tumor clearance also resulted in durable protection against syngeneic tumor rechallenge, which also depended on CD8+ T cells. To address safety concerns, we generated an immune-sensitized ZIKV strain, which was effective alone or in combination with immunotherapy. Thus, oncolytic ZIKV treatment can be leveraged by immunotherapies, which may prompt combination treatment paradigms for adult patients with GBM.Inflammatory damage contributes to β cell failure in type 1 and 2 diabetes (T1D and T2D, respectively). Mitochondria are damaged by inflammatory signaling in β cells, resulting in impaired bioenergetics and initiation of proapoptotic machinery. Hence, the identification of protective responses to inflammation could lead to new therapeutic targets. Here, we report that mitophagy serves as a protective response to inflammatory stress in both human and rodent β cells. Utilizing in vivo mitophagy reporters, we observed that diabetogenic proinflammatory cytokines induced mitophagy in response to nitrosative/oxidative mitochondrial damage. Mitophagy-deficient β cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β cell death, and hyperglycemia. Overexpression of CLEC16A, a T1D gene and mitophagy regulator whose expression in islets is protective against T1D, ameliorated cytokine-induced human β cell apoptosis. Thus, mitophagy promotes β cell survival and prevents diabetes by countering inflammatory injury. Targeting this pathway has the potential to prevent β cell failure in diabetes and may be beneficial in other inflammatory conditions.Extensive research has revealed the pivotal role of kinesin family member 20A (KIF20A) in cancer. However, its latent involvement in renal clear cell carcinoma (ccRCC) still remains unclear. Thus, here we explored the role of KIF20A in ccRCC. For this, a series of software including R (v. 3.6.1), SPSS (v. 23), ImageJ and FlowJo were used for the analyses. Open-access data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-expression Network Analysis (WGCNA) was used for module gene identification. In vitro results indicated that KIF20A expression is up-regulated in ccRCC tissue. KIF20A knockdown was able to inhibite cell proliferation and invasion of kidney A498 and Caki-1 cells. Meanwhile, KIF20A showed a strong association with immune infiltration. Particularly, KIF20A had a strong positive correlation with Th2 cells, Treg cells and Macrophages, but a negative correlation with Th17 cells, Mast cells and NK cells. These correlations may suggest the use of KIF20A as an underlying immunotherapy target in ccRCC. Our data indicated that KIF20A may promote cell invasion and proliferation in ccRCC, thus serving as an independent tumor marker and a putative therapeutic target.Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China. Recent studies have shown fatty acid metabolism is involved in the progression of various cancers through regulating the function of various types of cells. However, the relationship between fatty acid metabolism and tumorigenesis of ESCC remains unclear. Here, in this study, the expression of FBP1 was dramatically decreased in ESCC tissues compared with the adjacent non-ESCC tissues. The cell proliferation, migration, invasion and fatty acid metabolism were evaluated in ESCC cells using transfection of shFBP1 vectors. We found loss of FBP1 promoted ESCC cell proliferation, migration and invasion, which correlated with the activated fatty acid metabolism in vitro. Moreover, the content of phospholipids, triglycerides, neutral lipids and the protein expression levels of fatty acid metabolism related FASN, ACC1 and SREBP1C proteins were significantly increased following down-regulation of FBP1. Furthermore, FBP1 was found to be directly targeted by miR-18b-5p in ESCC cells.