ABSTRACT
Transforming growth factor-β (TGF-β) belongs to a group of biologically active cytokines that bind to its receptors to activate Smad signaling and non-Smad signaling pathways. The biological functions of TGF-β include promoting cell epithelial-mesenchymal transition, tissue fibrosis, angiogenesis and tumor immune evasion, as well as dual effects of cancer suppression and cancer promotion. Given the fact that the ligand- and receptors-mediated abnormal activation of TGF-β signaling pathways play an important role in the pathogenesis of multiple diseases such as malignant tumors and tissue fibrosis, more than a dozen small-molecule inhibitors have been developed to block the TGF-β signaling pathways, providing a novel method for controlling the development of these diseases. At present, pirfenidone, an inhibitor for TGF-β production, has been approved for treatment of idiopathic pulmonary fibrosis, while the inhibitors of TGFβRI/ALK5 for therapeutics of tumors or myelodysplastic syndromes, including LY2157299, EW-7197 and LY3200882, are in the phase I to III clinical trials, with additional ones inhibiting TGFβRs such as SB-431542, LY2109761, TP-0427736, and IN-1130 being in the preclinical phase. This paper reviews recent advances in research of small-molecule inhibitors targeting TGF-β and its receptors.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the association between chronic periodontitis and hypertension in rural adult Uygur residents.</p><p><b>METHODS</b>A total of 1415 Uygur residents aged 18 and over were selected by random multistage and probability proportional to size from 364 villages in Moyu county of Xinjiang Uygur autonomous region, all subjects received questionnaire, physical examination and biochemical analysis and oral examination. The subjects were categorized as periodontitis group and no periodontitis group, the periodontitis group was further categorized as mild, moderate and severe periodontitis subgroup. The relationship between chronic periodontitis with hypertension was analyzed by Spearman correlation. Binary logistic regression was used to calculate the influential factors for hypertension.</p><p><b>RESULTS</b>The prevalence rates of chronic periodontitis and hypertension were 66.0% (934/1415) and 33.8% (478/1415), respectively. The prevalence rates of hypertension were 18.7% (90/481), 35.1% (131/373), 32.3% (62/192), 52.8% (195/369) in no periodontitis, mild, moderate and severe periodontitis groups, respectively. Spearman correlation showed an association of chronic periodontitis with hypertension (r(s) = 0.273, P < 0.01). After adjustment for age, gender, body mass index, waist circumference, glycometabolism disorder, hyperlipidemia, chronic kidney disease, multiple logistic regression analysis showed that periodontitis was significantly associated with hypertension (OR = 1.75, 95%CI: 1.30 - 2.36, P < 0.01). Compared with no periodontitis, mild (OR = 1.76, 95%CI: 1.26 - 2.48, P < 0.01) and severe (OR = 2.26, 95%CI: 1.57 - 3.26, P < 0.01) periodontitis were significantly associated with hypertension while moderate periodontitis was not significantly associated with hypertension (OR = 1.21, 95%CI: 0.80 - 1.84, P > 0.05).</p><p><b>CONCLUSION</b>This study showed an independent association of periodontitis with hypertension in this study cohort.</p>