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Renal interstitial fibrosis is characterized by increased extracellular matrix (ECM) synthesis. Epithelial-mesenchymal transition (EMT) in kidneys is driven by regulated expression of fibrogenic cytokines such as transforming growth factor-beta (TGF-β). Yam, or Dioscorea alata (DA) is an important herb in Chinese medicine widely used for the treatment of clinical diabetes mellitus. However, the fibrosis regulatory effect of DA is unclear. Thus, we examined TGF-β signaling mechanisms against EMT in rat fibroblast cells (NRK-49F). The characterization of DA water-extracts used various methods; after inducing cellular fibrosis in NRK-49F cells by treatment with β-hydroxybutyrate (β-HB) (10 mM), we used Western blotting to examine the protein expression in the TGF-β-related signal protein type I and type II TGF-β receptors, Smads2 and Smad3 (Smad2/3), pSmad2 and Smad3 (pSmad2/3), Smads4, Smads7, and EMT markers. These markers included E-cadherin, alpha-smooth muscle actin (α-SMA), and matrix metalloproteinase-2 (MMP-2). Bioactive TGF-β and fibronectin levels in the culture media were determined using ELISA. Expressions of fibronectin and Snail transcription factor, an EMT-regulatory transcription factor, were assessed by immunofluorescence staining. DA extract dose-dependently (50–200 µg/mL) suppressed β-HB-induced expression of fibronectin in NRK-49F cells concomitantly with the inhibition of Smad2/3, pSmad2/3, and Smad4. By contrast, Smad7 expression was significantly increased. DA extract caused a decrease in α-SMA (α-smooth muscle actin) and MMP-2 levels, and an increase in E-cadherin expression. We propose that DA extract might act as a novel fibrosis antagonist, which acts partly by down regulating the TGF-β/smad signaling pathway and modulating EMT expression.

AbstractBackgroundPostoperative sepsis is a major type of sepsis. Sociodemographic characteristics, incidence trends, surgical procedures, comorbidities, and organ system dysfunctions related to the disease burden of postoperative sepsis episodes are unclear.MethodsWe analyzed epidemiological characteristics of postoperative sepsis based on the ICD-9-CM codes for the years 2002 to 2013 using the Longitudinal Health Insurance Databases of Taiwan’s National Health Insurance Research Database.ResultsWe identified 5,221 patients with postoperative sepsis and 338,279 patients without postoperative sepsis. The incidence of postoperative sepsis increased annually with a crude mean of 0.06% for patients aged 45–64 and 0.34% over 65 years. Patients with postoperative sepsis indicated a high risk associated with the characteristics, male sex (OR:1.375), aged 45–64 or ≥ 65 years (OR:2.639 and 5.862), low income (OR:1.390), aged township (OR:1.269), agricultural town (OR:1.266), and remote township (OR:1.205). Splenic surgery (OR:7.723), Chronic renal disease (OR:1.733), cardiovascular dysfunction (OR:2.441), and organ system dysfunctions had the highest risk of postoperative sepsis.ConclusionRisk of postoperative sepsis was highest among men, older, and low income. Patients with splenic surgery, chronic renal comorbidity, and cardiovascular system dysfunction exhibited the highest risk for postoperative sepsis. The evaluation of high-risk factors assists in reducing the disease burden.