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  • Hartley Jepsen posted an update 1 week, 2 days ago

    The aim of this study was to explore the signaling pathways associated with the effects of tumor necrosis factor alpha (TNF-α) on matrix metalloproteinase-1 (MMP-1) and MMP-3 expression in the human dermal fibroblast cell line CCD-966SK. TNF-α upregulated MMP-1 and MMP-3 mRNA and protein expression, and NFκB/p65 activation was found to be involved in TNF-α-induced MMP-1 and MMP-3 upregulation. TNF-α induced p65 phosphorylation at Ser536 and acetylation at Lys310. p300 knockdown suppressed TNF-α-induced p65 acetylation and reduced MMP-1 and MMP-3 expression in TNF-α-treated cells, but did not greatly restore MMP-1 and MMP-3 expression when p65 phosphorylation was inhibited by Bay11-7082 (IκBα inhibitor). NF-κB/luciferase reporter assay revealed that p300-mediated p65 acetylation was crucial for TNF-α-induced nuclear factor-kappa B (NF-κB) transcriptional activity. The chromatin immunoprecipitation (ChIP) assay indicated that TNF-α increased p300 recruitment to the MMP-1 and MMP-3 promoter regions surrounding the NFκB-binding site. Resveratrol notably inhibited TNF-α-induced MMP-1 and MMP-3 upregulation and abrogated TNF-α-induced p65 acetylation, leading to the downregulation of MMP-1 and MMP-3 expression in TNF-α-treated cells. Our data indicate that TNF-α-induced p300-mediated p65 acetylation leads to the upregulation of MMP-1 and MMP-3 expression in dermal fibroblasts, whereas resveratrol reduces this TNF-α-induced upregulation by downregulating p300 expression.Cardiac fibroma is a rare disease, and surgical resection generally remains the treatment of choice for these tumors in children. However, open surgery for some patients has to be rejected due to high risk. Here, we report a case of somewhat successful radiofrequency ablation of a huge left ventricular fibroma in a 3-year-old asymptomatic child. At the 3-month follow-up, the child was clinically well. Our case highlights that radiofrequency ablation may be used as an alternative treatment for the cardiac tumors, which are unsuitable for cardiac operation.

    Therapy for end-stage achalasia is debated data on long-term functional results of myotomy and esophagectomy are lacking. We compared quality of life and objective outcomes after pulldown Heller-Dor and esophagectomy.

    The study included 32 patients (57 years, IQR 49-70) who underwent the Heller-Dor operation with verticalisation of the distal esophagus in case of first instance treatment or failed surgery caused by insufficient myotomy and 16 patients (58 years, IQR 49-67) (p=0.806) who underwent esophagectomy after failed surgery for other causes. Data were extracted from a database designed for prospective clinical research. Postoperative dysphagia, reflux symptoms, endoscopic esophagitis were graded by semi-quantitative scales. Quality of life was assessed with the SF-36 questionnaire.

    Median follow-up period was 68 months (IQR 40.43-94.48) after pull-down Heller-Dor and 61 months (IQR 43.72-181.43 months) after esophagectomy (p=0.598). No statistically significant differences were observed with regansufficient myotomy.

    The optimal strategy for cerebral protection during repair of type A acute aortic dissection (TAAAD) has yet to be determined. We sought to determine the impact of differing degrees of hypothermia in patients undergoing acute dissection repair.

    All patients in the International Registry of Acute Aortic Dissection Interventional Cohort (IRAD-IVC) database who underwent TAAAD repair between 2010 and 2018 were identified. Data for operative temperature was available in 1962 patients, subsequently divided into 2 groups according to lowest temperature moderate hypothermic circulatory arrest (MHCA) (20 – 28°C) vs. deep hypothermic circulatory arrest (DHCA) (< 20°C). We then propensity-matched 362 pairs of patients and analyzed operative data and short-term outcomes.

    The median lowest temperature was 25.0°C in the matched MHCA group, as compared with 18.0°C in DHCA. For the entire cohort of 1962 patients, in-hospital mortality was 14.2% (278 deaths), not significantly different between DHCA and MHCA. Perioperative stroke rate was comparable between groups, before and after propensity-matching. Circulatory arrest times were significantly longer in the MHCA cohort, regardless of matching. Use of antegrade or retrograde cerebral perfusion was similar in matched groups. There were no differences in 30-day survival, or in other major postoperative morbidity between the two matched cohorts.

    A surgical strategy of MHCA + ACP is at least as safe as DHCA during repair of acute type A aortic dissection.

    A surgical strategy of MHCA + ACP is at least as safe as DHCA during repair of acute type A aortic dissection.Rhein is one of the anthraquinones components of Rheum. It shows excellent clinical efficacy and is widely used in the management of several disease conditions including tumors, inflammation, diabetic nephropathy, and viral infections. In this review, we summarize the recent studies on the pharmacological activities of rhein and its derivatives, as well as their association with different diseases and possible mechanisms based on our previous review. This review serves as an updated and a supplement to our previous report highlighting the use of rhein in nanotechnology. It also serves as a reference study and offers an overall picture of the use of rhein and its derivatives in nanotechnology.Gastric cancer (GC), known for high morbidity and mortality, is poorly prognosed with traditional chemotherapy and biological agents. Ademetionine research buy Current studies have found that over-activation of AKT is a common molecular characteristic in GC. Although the development of this targeted inhibitor has entered clinical phases, limited success is reported because of its compensatory signaling pathways. Here, we found that GC cell lines with high phosphorylation of AKT show different sensitivity to AKT inhibitors (AKTis), but a reduction of p-GSK3β related sensitivity of AKTis in GC cells. Besides, we revealed that Ceritinib exerted a strongly synergistic antitumor effect with AKT inhibitors both in vitro and in vivo. Obviously, Ceritinib improved the sensitivity of Capivasertib (AZD5363, AKTs) and Afuresertib (GSK2110183, AKTis) in gastric cancer cells, as illustrated by a significant reduction in the GC cell proliferation and enhanced apoptosis. The drug combination showed tumor regression in BALB/c (nu/nu) mouse MKN45 (Gastric cancer), tumor model.