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Standardized extraction procedures for herb areas important as their authentication to maintain theirquality and ensure their safe use. We had prepared astandardized and purified Scutellaria baicalensis Georgiextract, PF2405, which was enriched with three majorcomponents, baicalein, oroxylin A and wogonin. In thepresent study, we investigated the potential anti-inflammatoryeffects of PF2405 in vitro and in two differentexperimental animal models of inflammatory bowel disease. Effect of PF2405 studied in tumor necrosis factor(TNF)-a-induced HT-29 cells in vitro. In vivo experimentalcolitis models were induced by administration oftrinitrobenzene sulfonic acid (TNBS) or dextran sulfatesodium (DSS). PF2405 (50 lg/ml) decreased TNF-ainducedcyclooxygenase (COX)-2 expressions throughinhibition of phosphorylation of c-Jun N-terminal kinasesand p38 mitogen-activated protein kinase in HT-29 cells. Combination of baicalein (20 lg/ml), oroxylin A (8 lg/ml),and wogonin (2 lg/ml) markedly inhibits TNF-a-inducedCOX-2 expression when compared with individual components. PF2405 (25 mg/kg b.w.) treatment significantlyreduced histopathological severity; suppressed expression ofCOX-2, TNF-a, and interleukin-1b in TNBS-induced mice. Moreover, PF2405 (25 mg/kg b.w.) has both potent preventiveand therapeutic activities in DSS-induced colitis. Collectively, PF2405 shows prominent anti-inflammatoryeffect that can be used as a new therapeutic approach forintestinal inflammatory disorders.
Background: Standardized extraction procedures for herb are as important as their authentication to maintain their quality and ensure their safe use. We had prepared a standardized and purified Scutellaria baicalensis Georgi extract, PF2405, which was enriched with three major components, baicalein, oroxylin A and wogonin. In the present study, we investigated the potential anti-inflammatory effects of PF2405 in vitro and in using by two different experimental animal models of inflammatory bowel disease Methods: Effect of PF2405 studied in tumor necrosis factor (TNF)-a-induced HT-29 cells in vitro. In vivo experimental colitis models were induced by administration of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS). Results: PF2405 decreased TNF-a-induced Cyclooxygenase (COX)-2 expressions through inhibition of phosphorylation of c-Jun N-terminal kinases (JNK) and p38 mitogen- activated protein kinase (MAPK) in HT-29 cells. Combination of baicalein, oroxylin A, and wogonin markedly inhibits TNF-a-induced COX-2 expression when compared with individual components. PF2405 treatment significantly reduced histopathological severity and strongly suppressed the expression of COX-2, TNF-a as well as interleukin (IL)-1ß in TNBS-induced mice. Moreover, PF2405 has both potent preventive and therapeutic activities in DSS-induced colitis. Conclusions: PF2405 shows prominent anti-inflammatory effect that can be used as a new therapeutic agent for inflammatory bowel disease.
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Purpose The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. Materials and Methods From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCL patients (87.8%). Results NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p < 0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of NK lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. Conclusion NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.
This study aims to investigate the relationship between structural damage and sensitivity indices using the Hilbert-Huang transform (HHT) method. Two damage detection indices are proposed: the ratio of bandwidth (RB), and the ratio of effective stiffness (RES). The nonlinear four bays multiple degree of freedom models with various predominant frequencies are constructed using the SAP2000 program. Adjusted PGA earthquake data (Japan 311, Chi-Chi 921) are used as the excitations. Next, the damage detection indices obtained using the HHT and the fast Fourier transform (FFT) methods are evaluated based on the acceleration responses of the structures to earthquakes. Simulation results indicate that, the column of the 1st floor is the first yielding position and the RB value is changed when the RES<90% in all cases. Moreover, the RB value of the 1st floor changes more sensitive than those from the top floor. In addition, when the structural response is nonlinear (i.e., RES<100%), the RB and the RES curves indicate the incremental change in the HHT spectra. However, the same phenomenon can be found from FFT spectra only when the stiffness reduction is large enough. Therefore, the RB estimated from the smoothed HHT spectra is an effective and sensitive index for detecting structural damage.
Polyimide (PI)/graphene sheets (GSs) composites were prepared by solution blending. The incorporationof GSs into PI increased the thermal conductivity, thermal stability and mechanical properties of PI. The thermal conductivityof PI/GSs composites was significantly improved compared with that of neat PI from 0.254 to 1.002 W/mK; this can be attributed to the homogeneous dispersion of graphene and the formation of heat conduction pathway. Furthermore, the Young modulus of PI/GSs was raised up to 4.04 GPa, approximately two-fold enhancement incomparison with that of neat PI. In addition, the incorportation of GSs in PI indicated excellent optical transparencyat the lowest weight fractions of GSs and modified wettability of PI films.
Background: Tissue-engineered cartilage has provided a promising method in the treatment of physeal growth arrest. This study was designed to investigate transplantation of microencapsulated allogeneic chondrocytes to treat the injured growth plate. Methods: Allogeneic chondrocytes were encapsulated within alginate-polylysinealginate semipermeable membranes. Microencapsulated chondrocytes co-cultured with Bone Mesenchymal Stem Cells (BMSCs) were evaluated whether it could promote chondrogenesis of BMSCs. An experiment model of an injured growth plate was made by resecting the lateral half of the right distal femur physis in rabbits. Microencapsulated allogeneic chondrocytes, allogeneic chondrocytes as well as empty microcapsules were grafted into growth plate defects of 6-week-old rabbits. Histological and radiographic examinations were examined after transplantation up to 16 weeks. Results: The histological study showed that BMSCs co-cultured with microencapsulated chondrocytes could produce GAG and II collagen similarly with chondrocytes. Angular deformity and length discrepancy in the group with microencapsulated allogeneic chondrocytes were less than those in other groups (p < 0.001). The histological study confirmed the viability of microencapsulated chondrocytes at 16 weeks postoperatively. The neogenetic chondrocytes of columnar arrangement have been found in the growth plate defect to prevent early ossification and closure of the growth plate. Conclusions: The histological study confirmed the viability of microencapsulated chondrocytes at 16 weeks postoperatively. The neogenetic chondrocytes of columnar arrangement have been found in the growth plate defect to prevent early ossification and closure of the growth plate.
Wen, Wanqing,Zheng, Wei,Okada, Yukinori,Takeuchi, Fumihiko,Tabara, Yasuharu,Hwang, Joo-Yeon,Dorajoo, Rajkumar,Li, Huaixing,Tsai, Fuu-Jen,Yang, Xiaobo,He, Jiang,Wu, Ying,He, Meian,Zhang, Yi,Liang, Jun IRL Press 2014 Human molecular genetics Vol.23 No.20
<P>Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by <I>in silico</I> and <I>de novo</I> replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the <I>KCNQ1</I> (rs2237892, <I>P</I> = 9.29 × 10<SUP>−13</SUP>), <I>ALDH2/MYL2</I> (rs671, <I>P</I> = 3.40 × 10<SUP>−11</SUP>; rs12229654, <I>P</I> = 4.56 × 10<SUP>−9</SUP>), <I>ITIH4</I> (rs2535633, <I>P</I> = 1.77 × 10<SUP>−10</SUP>) and <I>NT5C2</I> (rs11191580, <I>P</I> = 3.83 × 10<SUP>−8</SUP>) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (<I>P</I> < 5.0 × 10<SUP>−8</SUP>) and an additional 14 at <I>P</I> < 1.0 × 10<SUP>−3</SUP> with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.</P>
Morphine tolerance remains a challenge in the management of chronic pain in the clinic. As shown in our previous study, the dopamine D2 receptor (D2DR) expressed in spinal cord neurons might be involved in morphine tolerance, but the underlying mechanisms remain to be elucidated. In the present study, selective spinal D2DR blockade attenuated morphine tolerance in mice by inhibiting phosphatidylinositol 3 kinase (PI3K)/serine–threonine kinase (Akt)-mitogen activated protein kinase (MAPK) signaling in a μ opioid receptor (MOR)-dependent manner. Levocorydalmine (l-CDL), which exhibited micromolar affinity for D2DR in D2/CHO-K1 cell lines in this report and effectively alleviated bone cancer pain in our previous study, attenuated morphine tolerance in rats with chronic bone cancer pain at nonanalgesic doses. Furthermore, the intrathecal administration of l-CDL obviously attenuated morphine tolerance, and the effect was reversed by a D2DR agonist in mice. Spinal D2DR inhibition and l-CDL also inhibited tolerance induced by the MOR agonist DAMGO. l-CDL and a D2DR small interfering RNA (siRNA) decreased the increase in levels of phosphorylated Akt and MAPK in the spinal cord; these changes were abolished by a PI3K inhibitor. In addition, the activated Akt and MAPK proteins in mice exhibiting morphine tolerance were inhibited by a MOR antagonist. Intrathecal administration of a PI3K inhibitor also attenuated DAMGO-induced tolerance. Based on these results, l-CDL antagonized spinal D2DR to attenuate morphine tolerance by inhibiting PI3K/Akt-dependent MAPK phosphorylation through MOR. These findings provide insights into a more versatile treatment for morphine tolerance.