Translational research : the journal of laboratory and clinical medicine
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Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-β-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing β-cell proliferation. ⋯ Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of β-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in β-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for β-cell proliferation.
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Currently, clinicians rely on clinical nomograms to stratify progression risk at the time of diagnosis in patients with prostate cancer (CaP). However, these tools may not accurately distinguish aggressive potential in low-grade CaP. The current study determined the diagnostic potential of 3 molecular markers (ROCK1, RUNX3, and miR-301a) in terms of their ability to identify which low-grade tumors are likely to progress. ⋯ Expressions of ROCK1 and miR-301a were found to be significantly higher in Gleason 6 and 7 CaP as compared to BPH, while an inverse trend was observed with RUNX3. Further, incorporation of all 3 molecular markers significantly improved clinical nomograms' diagnostic accuracy and correlated with disease progression. Hence, in conclusion, the inclusion of these 3 molecular markers identified aggressive phenotype and predicted disease progression in low-grade CaP tumors at the time of diagnosis.
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Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. ⋯ At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.
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Obesity has become a common rising health care problem, especially in "modern" societies. Obesity is considered a low-grade systemic inflammation, partly linked to leaky gut. Circadian rhythm disruption, a common habit in modern life, has been reported to cause gut barrier impairment. ⋯ Analysis of gut microbiota and their metabolites, as important regulators of barrier homeostasis, revealed that abnormal food timing reduced relative abundance of butyrate-producing bacteria, and the colonic butyrate level. Overall, our data supported that dysbiosis was characterized by increased intestinal permeability and decreased beneficial barrier butyrate-producing bacteria and/or metabolite to mechanistically link the time of eating to obesity. This data provides basis for noninvasive microbial-targeted interventions to improve intestinal barrier function as new opportunities for combating circadian rhythm disruption induced metabolic dysfunction.
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Acute kidney injury (AKI) diagnosis relies on plasma creatinine concentration (Crpl), a relatively insensitive, surrogate biomarker of glomerular filtration rate that increases only after significant damage befalls. However, damage in different renal structures may occur without increments in Crpl, a condition known as subclinical AKI. Thus, detection of alterations in other aspects of renal function different from glomerular filtration rate must be included in an integral diagnosis of AKI. ⋯ Predisposed animals showed a reduced response to the FST (namely, reduced furosemide-induced diuresis and K+ excretion), whereas nonpredisposed animals showed no alteration, compared to the controls. Computational modeling of epithelial transport of solutes and water along the nephrons applied to experimental data suggested that proximal tubule transport was only minimally reduced, the sodium-chloride symporter was upregulated by 50%, and the renal outer medullary potassium channel was downregulated by 85% in predisposed animals. In conclusion, serial coupling of the FST and computational modeling may be used to detect and localize subclinical tubular alterations.