Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-kB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n ¼ 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n ¼ 111) or placebo (n ¼ 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P ¼ 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months followup. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P ¼ 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P ¼ 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. Ó2016 AACR.

Atherosclerosis is the most common Cardiovascular Disease (CVD) causing increased morbidity. Although atherosclerosis is a general disease involving several factors, it preferentially affects the wall of the vessel bifurcations. The employment of advanced Computational Fluid Dynamics (CFD) has the potential in shedding more light in the further understanding of the causes of the diseases and perhaps aid in the early diagnosis. In this study, a three-dimensional Fluid Structure Interaction (FSI) study was carried out for a patient specific carotid. By considering physiological conditions, first normal and then with hypertension disease, hemodynamic parameters are evaluated to better understand the genesis and progress of atherosclerotic plaques in the carotid artery bifurcation. Two-way FSI was performed by applying a fully implicit second-order backward Euler differencing scheme using commercial code ANSYS and ANSYS CFX (version 19.0). Arbitrary Lagrangian-Eulerian (ALE) formulation is employed to calculate the arterial response by using the temporal blood response. Due to arterial bifurcation, obvious velocity reduction and backflow formation is observed which decrease shear stress and made it oscillatory at the starting point of the internal carotid artery near the carotid sinus, which resulted in low shear stress. Oscillatory shear index (OSI) signifies oscillatory behavior wall shear stress. By using the anatomically realistic 3D geometry and representative physiological conditions, the results obtained for shear stress are more acceptable. Comparing the results of this study with available literature shows that the regions with low wall shear stress and with OSI value more than 0.3 face potential risk to the plaque development. It is observed that hemodynamics of carotid artery is very much affected by the geometry and flow conditions and relatively low wall shear stress regions were observed post stenosis, which is a known reason for plaque development and progression.

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The selective translocation of molecules through membrane pores is an integral process in cells. We present a bacterial sugar transporter, CymA of unusual structural conformation due to a dynamic N terminus segment in the pore, reducing its diameter. We quantified the translocation kinetics of various cyclic sugars of different charge, size, and symmetry across native and truncated CymA devoid of the N terminus using singlechannel recordings. The chemically divergent cyclic hexasaccharides bind to the native and truncated pore with high affinity and translocate effectively. Specifically, these sugars bind and translocate rapidly through truncated CymA compared to native CymA. In contrast, larger cyclic heptasaccharides and octasaccharides do not translocate but bind to native and truncated CymA with distinct binding kinetics highlighting the importance of molecular charge, size and symmetry in translocation consistent with liposome assays. Based on the sugar-binding kinetics, we suggest that the N terminus most likely resides inside the native CymA barrel, regulating the transport rate of cyclic sugars. Finally, we present native CymA as a large nanopore sensor for the simultaneous single-molecule detection of various sugars at high resolution, establishing its functional versatility. This natural pore is expected to have several applications in nanobiotechnology and will help further our understanding of the fundamental mechanism of molecular transport.