Kroghcarson9542

AIMS The objectives of the present study were to investigate the mechanisms of Ninj-1 regulation in TNFα-activated human endothelial cells (HEC), and to test if Amlodipine (AML) ameliorates the inflammatory stress by decreasing Ninj-1 expression. MAIN METHODS TNFα-activated HEC with/without AML (0.1 μM and 1 μM) were used. TNFα-receptor 1 (TNFR1) was silenced and inhibitors for oxidative stress (N-acetyl cysteine), endoplasmic reticulum stress (salubrinal, 4-phenyl butyric acid), or NF-kB (Bay 11-7085) and p38 MAPK (SB203580) were used. Levels of Ninj-1, TNFR1, monocyte adhesion, endoplasmic reticulum stress (ERS) sensors, NADPH oxidase- and mitochondria-derived oxidative species were evaluated. KEY FINDINGS The novel findings that we report here are (i) silencing the endothelial TNFR1 leads to decreased Ninj-1 expression and diminished monocyte adhesion; (ii) increased oxidative stress, ERS and NF-kB activation enhance Ninj-1 expression and monocyte adhesion; (iii) up-regulation of endothelial Ninj-1 expression stimulates monocytes adhesion to TNFα - activated HEC; (iv) AML diminishes monocyte adhesion by reducing Ninj-1 expression through mechanisms involving the decrease of NADPH oxidase and mitochondria-dependent oxidative stress, ERS and NF-kB. In addition, AML alleviates apoptosis by reducing the pro-apoptotic CHOP expression and re-establishing the mitochondrial transmembrane potential. SIGNIFICANCE The results of the present study suggest that Ninj-1 and the proteins involved in its regulation can be considered therapeutic targets for the alleviation of inflammation- dependent disorders. In addition, we demonstrate that some of the benefic effects of AML can be achieved through regulation of Ninj-1. AIM To explore the role and mechanism of Hydrogen peroxide-inducible clone-5 (Hic-5) in hepatic ischemia reperfusion injury. METHODS Hic-5 KO and WT mice were used to establish the liver ischemia reperfusion model (HI/R). Primary hepatocytes were isolated to establish hypoxic reoxygenation model (H/R). AST and ALT were measured by automatic biochemical analyzer. Liver tissue sections were stained with HE and Tunnel. RNA and proteins were extracted from liver tissues, and expressions of Il-6, Il-10, CCL-2, CXCL-10, P65, Caspase-3, TLR4 and FADD were detected at gene and protein levels. Liver cell apoptosis was detected by flow cytometry and immunofluorescence. Primary hepatocytes were stimulated by LPS to establish a model of hepatocyte apoptosis, and cell inflammation and apoptosis-related proteins were detected. RESULTS After HI/R, ALT and AST in serum were up-regulated, some hepatocyte apoptosis were observed in pathological sections. Hic-5 expression was increased in WT mice after HI/R, and liver damage were severer than KO mice. The expression of IL-6, CCL-2 and CXCL-10 in the liver of KO mice was low, and the expression of IL-10 was high. Further studies showed that KO mice showed lower expression of P65, Caspase3 and TLR4. In H/R model, hepatocytes also showed the same trend. Finally, after LPS stimulation, the results showed that the inflammation and apoptosis induced by LPS were significantly reduced in Hic-5 knocked hepatocytes. learn more CONCLUSION Hic-5 was found to promote inflammation through NF-kb signaling pathway and apoptosis through TLR4-FADD signaling pathway in mice with HI/R, thus aggravating liver injury in mice. Brown adipose tissue (BAT) has multiple functions in the human body, including the production of heat and increasing energy consumption. However, BAT is also related to many kinds of diseases, such as obesity and metabolic disorders. The progression of such diseases occurs at the cellular level, and thus, imaging techniques could prove greatly beneficial for determining optimal therapeutic regimens. Currently, positron-emission tomography (PET) is considered to be the gold standard for assessing the function of activated BAT. However, PET also has inherent disadvantages, and, thus, recent efforts have been focused on exploring, and potentially developing, new imaging techniques to better observe BAT and evaluate its metabolic function. Researchers have already achieved promising success with computed tomography, magnetic resonance approaches, ultrasound, new tracers for use in PET, and other imaging techniques through in vivo and in vitro animal experiments. Since, these studies have shown that BAT may serve as an effective therapeutic target for treatment of metabolic dysfunction diseases, the development of an efficient in vivo BAT imaging technique that is applicable to humans will prove to be of great clinical value. In this review, classical PET imaging technique is highlighted as well as the current status of preclinical imaging methods developed for BAT examination. OBJECTIVE Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. METHODS Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor β-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. RESULTS KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. CONCLUSION Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC.