Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Dec 2017
Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway.
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an estimated 5 year survival rate of approximately 5% of all stages combined. High potential of PDAC metastasis is a leading cause for high mortality and poor prognosis. The majority of patients present with distant metastasis at diagnosis. ⋯ The underlying mechanism is that FKN/CX3CR1 activated JAK/STAT signaling, which in turn regulated cell growth. Consistently, in vivo tumorigenesis assay validated the regulatory role of FKN/CX3CR1 in PDAC growth. Our investigation helped understanding the pathogenesis of PDAC occurrence, and demonstrated critical role of FKN/CX3CR1 in PDAC development.
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Biochem. Biophys. Res. Commun. · Nov 2017
Gut microbial metabolite TMAO contributes to renal dysfunction in a mouse model of diet-induced obesity.
Emerging evidence shows that obesity induces renal injury and is an independent risk factor for the development of chronic kidney disease (CKD), even without diabetes or hyperglycemia. Although multiple metabolic factors have been suggested to account for obesity-associated renal injury, the precious underlying mechanisms are not completely understood. Recent study shows that increased trimethylamine N-Oxide (TMAO), a gut microbiota-generated metabolite, directly contributes to renal interstitial fibrosis and dysfunction. ⋯ These data suggest that HFD-induced obesity leads to elevations in gut microbiota-generated metabolite TMAO in the circulation, which contributes to renal interstitial fibrosis and dysfunction by promoting renal oxidative stress and inflammation. These findings may provide new insights into the mechanisms underlying obesity-associated CKD. Targeting TMAO may be a novel strategy for prevention and treatment of CKD in patients with obesity.
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Biochem. Biophys. Res. Commun. · Oct 2017
Gadolinium chloride ameliorates acute lung injury associated with severe acute pancreatitis in rats by regulating CYLD/NF-κB signaling.
The present study was embarked on an investigation of the mechanisms behind the effects of Gadolinium chloride (GdCl3) on lung injury associated with severe acute pancreatitis (SAP) in rats. Rats were randomly distributed into three groups: sham operation group (SO), SAP group and SAP treated with GdCl3 group (SAP + GdCl3). Retrograde injection of 5% sodium taurocholate into the biliopancreatic duct was adopted to induce SAP. ⋯ The NF-κB activation was obviously inhibited when CYLD expression was markedly up-regulated in AMs of SAP + GdCl3. Negative correlation was analyzed between CYLD and NF-κB in both SAP and SAP + GdCl3. These data demonstrate that GdCl3 ameliorates lung injury secondary to SAP in rats mainly by up-regulating CYLD expression and inhibiting NF-κB activation in AMs, which may play a vital role in lung injury.
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Biochem. Biophys. Res. Commun. · Aug 2017
The glycine hinge of transmembrane segment 2 modulates the subcellular localization and gating properties in TREK channels.
TWIK-Related K+ channels (TREK), including TREK-1 and TREK-2, belong to the TREK/TRAAK subclass of two-pore domain K+ (K2P) family. The important functions of transmembrane segment 4 (M4)-glycine hinge in TREK channel gating have been characterized, but the roles of M2-hinge (the equivalent residue of M4-hinge) remain unclear. Here, by characterizing the macroscopic currents, subcellular localization and gating properties of their M2-hinge mutants (G166A for TREK-1 and G196A for TREK-2), we investigated the functions of M2-hinge. ⋯ WT-ΔpCt, a TREK-2 tandom dimer, was used to assess the function of M2-hinge in the cis-type gating of TREK-2. The sensitivities of G196A-ΔpCt to both 2-APB and ΔpHo decreased compared with WT-ΔpCt. Taken together, our results reveal that the M2-hinge of TREK channels control their macroscopic current, subcellular localization and gating process.
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Biochem. Biophys. Res. Commun. · Aug 2017
Transgenerational effects of proton beam irradiation on Caenorhabditis elegans germline apoptosis.
When treating cancer using radiation therapy, it is critical to increase patient survival rates and to reduce side effects. In this respect, proton beam radiation treatment performs better than other radiation treatments because of its high target specificity. However, complications still remain after proton beam radiation treatment. ⋯ In this study, we analyzed the transgenerational effects of proton beam irradiation using the model organism Caenorhabditis. elegans. We found that germline apoptosis increased after proton beam irradiation and its effects were sustained transgenerationally. Moreover, we identified that a germline-specific histone methyltransferase component, SET-2, has a critical role in transmitting the transgenerational effect on germline apoptosis to the next generation after proton beam irradiation.