Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection

Stretchable broadband photo-sensor sheets for nonsampling, source-free, and label-free chemical monitoring by simple deformable wrapping

Chemical monitoring communicates diverse environmental information from industrial and biological processes. However, promising and sustainable systems and associated inspection devices that dynamically enable on-site quality monitoring of target chemicals confined inside transformable and opaque channels are yet to be investigated. This paper designs stretchable photo-sensor patch sheets for nonsampling, source-free, and label-free on-site dynamic chemical monitoring of liquids flowing inside soft tubes via simple deformable surface wrapping. The device integrates carbon nanotube–based broadband photo-absorbent thin films with multilayer-laminated stretchable electrodes and substrates. The patterned rigid-soft structure of the proposed device provides durability and optical stability against mechanical deformations with a stretchability range of 70 to 280%, enabling shape-conformable attachments to transformable objects. The effective use of omnidirectional and transparent blackbody radiation from free-form targets themselves allows compact measurement configuration and enhances the functionality and simplicity of this scheme, while the presenting technology monitors concentrations of arbitrary water-soluble chemicals

Compositions of diets (%).

<p>Compositions of diets (%).</p

Gene expression of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) and iNOS in BMDMs treated with soluble tannin hydrolysate.

<p>mRNA levels of IL-1ß (a), IL-6 (b), TNF-α (c), and iNOS (d) were determined by real-time PCR. BMDMs were pre-treated with soluble tannin hydrolysate (0, 30, and 100 μg/ml) for 1 hour followed by stimulation with three different strains of MAC (MAC-1, MAC-2, and MAC-3) for 6 hours. mRNA was extracted from BMDMs, reverse-transcribed into cDNA and qPCR performed. The values are presented as means ± SEM (n = 3–4). * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001 compared with no treatment with soluble tannin hydrolysate (0 μg/ml).</p

ORAC values of soluble tannin powder and soluble tannin hydrolysate.

<p>Soluble tannin powder was hydrolyzed by heating at 90°C for 3 hours with 5 ml of a 1.2 N HCl–50% methanol solution, followed by dilution to 10 ml using 1.2 N HCl–50% methanol solution. The values are presented as means ± SEM (n = 3). *** <i>P</i> < 0.001 compared with non-hydrolyzed soluble tannin powder.</p

Proinflammatory cytokine (IL-1ß, IL-6, TNF-α) secretion by BMDMs treated with soluble tannin hydrolysate.

<p>BMDMs were pre-treated with soluble tannin hydrolysate (0, 30, and 100 μg/ml) for 1 hour followed by stimulation with three different strains of MAC (MAC-1, MAC-2, and MAC-3) for 6 hours. The supernatant was harvested and IL-1ß (a), IL-6 (b), and TNF-α (c) protein concentration was determined by ELISA. The values are presented as means ± SEM (n = 4). * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001 compared with no soluble tannin hydrolysate (0 μg/ml).</p

Analysis of soluble tannin and soluble tannin hydrolysate bacteriostatic activity against MAC.

<p>MAC strains (2×10² CFU each) were inoculated in culture medium with soluble tannin (hydrolysate). Soluble tannin (a) and soluble tannin hydrolysate (b) was added at 0, 30, and 100 μg/ml soluble tannin powder to each of three tubes and the CFU determined. The values are presented as means ± SEM (n = 4). * <i>P</i> < 0.05 when compared with no treatment with soluble tannin hydrolysate (0 μg/ml).</p

The effect of soluble tannin in a MAC-infected pulmonary granuloma model.

<p>Diets were started 1 week before MAC infection. All mice were analyzed at 8 weeks after MAC infection. (a) Microscopic morphology of granulomas in the H&E-stained lungs of MAC-infected BALB/c mice fed control and 2% soluble tannin diets. Dotted lines indicate the border of granulomas. Original magnification, ×40 and ×200. (b) Analysis of the size of lung granulomas between control and 2% soluble tannin diet. (c) MAC CFU counts in one lobe of lungs using Middlebrook 7H10 agar plates as described in the Materials and Methods. The values are presented as means ± SEM (uninfected mice, n = 5; MAC-infected mice, n = 8). * <i>P</i> < 0.05, *** <i>P</i> < 0.001 compared with MAC-infected mice fed the control diet.</p

IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma

In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma. This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in glioblastoma reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for the occurance of aberrant nucleolar function and increased anabolic processes in glioblastoma, which constitutes a primary event in gliomagenesis