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Raman microspectroscopy and Raman photo uncover biomarkers distinct for thoracic aortic aneurysms.
Therefore, our findings indicate that 1,25(OH)2D3 protects against cardiac hypertrophy in mice through upregulating p21 expression.Colon cancer is still a major disease plaguing humans. In this study, we evaluated the synergistic antitumor effects of the combination of BRD4 inhibitor JQ1 and docosahexaenoic acid (DHA) in colon cancer. We demonstrated that simultaneous exposure to JQ1 and DHA resulted in strong synergistic antiproliferative and proapoptotic effects related to inhibition of expression of c-Myc and activation of NF-κB in colon cancer cell lines. At the same time, the synergetic anticancer effect had been confirmed in vivo. For in vivo experiments, JQ1 and DHA resulted in more significant tumor growth inhibition (53.7%) in a human colon cancer HCT116 xenograft model, comparing with the moderate inhibition in JQ1-treated (31.9%) or DHA-treated groups (20.3%). read more Because DHA is the predominant component of fish oil, our data suggest that this nontoxic dietary supplement could be administered with BRD4 inhibitor during therapy for CRC, which lay an important foundation for the development of therapeutic regimens for CRC.Pharmacological modulation of the Janus kinase (JAK) family has achieved clinically meaningful therapeutic outcomes for the treatment of inflammatory and hematopoietic diseases. Several JAK1 selective compounds are being investigated clinically to determine their anti-inflammatory potential. We used recombinant enzymes and primary human lymphocytes to assess the JAK1 specificity of itacitinib (INCB039110) and study inhibition of signal transducers and activators of transcription (STAT) signaling. Rodent models of arthritis and inflammatory bowel disease were subsequently explored to elucidate the efficacy of orally administered itacitinib on inflammatory pathogenesis. Itacitinib is a potent and selective JAK1 inhibitor when profiled against the other JAK family members. Upon oral administration in rodents, itacitinib achieved dose-dependent pharmacokinetic exposures that highly correlated with STAT3 pharmacodynamic pathway inhibition. Itacitinib ameliorated symptoms and pathology of established experimentally-induced arthritis in a dose-dependent manner. Furthermore, itacitinib effectively delayed disease onset, reduced symptom severity, and accelerated recovery in three distinct mouse models of inflammatory bowel disease. Low dose itacitinib administered via cannula directly into the colon was highly efficacious in TNBS-induced colitis but with minimal systemic drug exposure, suggesting localized JAK1 inhibition is sufficient for disease amelioration. Itacitinib treatment in an acute graft-versus-host disease (GvHD) model rapidly reduced inflammatory markers within lymphocytes and target tissue, resulting in a marked improvement in disease symptoms. This is the first manuscript describing itacitinib as a potent and selective JAK1 inhibitor with anti-inflammatory activity across multiple preclinical disease models. These data support the scientific rationale for ongoing clinical trials studying itacitinib in select GvHD patient populations.GDF11 has been reported to play a critical role in rejuvenating hypertrophy heart, skeletal muscle, and blood vessel regeneration in aged mice. Whether GDF11 can regulate autophagy in cardiomyocytes remains largely unknown. Thus, the purpose of the present study was to investigate the effects of GDF11 on cardiomyocyte autophagy induced by hypoxia, in addition to the underlying mechanisms. By using the MTT assay, Flow cytometry assay, LIVE/DEAD® Viability/Cytotoxicity Kit Stains and TUNEL assay, we found that exogenous GDF11 decreased apoptosis caused by prolonged hypoxia in cardiomyocytes. The expression of GDF11 was decreased obviously both in the cardiac tissue of myocardial infarction mice and the hypoxia treated cardiomyocytes. Protein levels of cleaved caspase-3, p-AMPK, SQSTM1, LC3B-I/II and GDF11 were detected by western blot. Autophagosomes and autolysosomes were identified by confocal laser microscopy after transfecting with the mRFP-eGFP-LC3 plasmids. Antibody against GDF11 (anti-GDF11) was used to inhibit the function of GDF11. At the molecular level, exogenous GDF11 increased AMPK function and enhanced autophagy activity. Anti-GDF11 inhibited autophagy and aggravated hypoxia-induced apoptosis in cardiomyocytes. Thus, GDF11 might be a potential target for myocardial infarction therapy.
This study sought to assess the relationship between E/e' and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its prognostic role.

Patients with CKD have diastolic dysfunction, reduced physical fitness, and elevated risk of cardiovascular disease.

Patients with stage 3 and 4 CKD without previous cardiac disease underwent resting and exercise stress echocardiograms with assessment of exercise E/e'. Patients were compared to age-, sex-, and risk factor-matched control individuals and were followed annually for 5 years for cardiovascular death and major adverse cardiovascular event(s) (MACE). Exercise capacity was assessed as metabolic equivalents (METs), with reduced exercise capacity defined as METs of≤7. Raised exercise E/e' was defined as >13.

A total of 156 patients with CKD (age 62.8 ± 10.6 years; male 62%) were compared to 156 matched control individuals. Patients with CKD were more likely to be anemic (p<0.01) and had increased left ventricular mass (p<0.01),with CKD, presumably consequent to diastolic dysfunction. Elevated exercise E/e' in patients with CKD is an independent predictor of cardiovascular death and MACE.Cardiac magnetic resonance (CMR) is at the forefront of noninvasive methods for the assessment of myocardial anatomy, function, and most importantly tissue characterization. The role of CMR is becoming even more significant with an increasing recognition that inflammation plays a major role for various myocardial diseases such as myocardial infarction, myocarditis, and takotsubo cardiomyopathy. Ultrasmall superparamagnetic particles of iron oxide (USPIO) are nanoparticles that are taken up by monocytes and macrophages accumulating at sites of inflammation. In this context, USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases. Here, we will review the recent diagnostic applications of USPIO in terms of imaging myocardial and vascular inflammation, and highlight some of their future potential.
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