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Competing Interests: Conflicts of interest Dr Tsen-Fang Tsai has conducted clinical trials or received honoraria for serving as a consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, EliLilly, Galderma, GSK-Stiefel, Janssen-Cilag, Leo-Pharma, Merck, Novartis, Pfizer Inc, and UCB Pharma. Dr Ya-Chu Tsai has delivered speeches held by AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, EliLilly, Janssen-Cilag, Leo-Pharma, Novartis, Pfizer Inc, Viatris.

Cancer represents a profound challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major problem in cancer therapy and can result in progression of the disease. In our previous studies, we developed small-molecule inhibitors targeting ubiquitin-specific peptidase 24 (USP24) to combat drug-resistant lung cancer. Recently, we found that the USP24 inhibitor NCI677397 induced ferroptosis, a type of programmed cell death, in drug-resistant cancer cells by increasing lipid reactive oxygen species (ROS) levels. In the present study, we investigated the molecular mechanisms and found that the targeting of USP24 by NCI677397 increased gene expression of most lipogenesis-related genes, such as acyl-CoA synthetase long-chain family member 4 (ACSL4), and activated autophagy. In addition, the activity of several antioxidant enzymes, such as glutathione peroxidase 4 (GPX4) and dihydrofolate reductase (DHFR), was inhibited by NCI677397 treatment via an increase in protein degradation, thereby inducing lipid ROS production and lipid peroxidation. In summary, we demonstrated that NCI677397 induced a marked increase in lipid ROS levels, subsequently causing lipid peroxidation and leading to the ferroptotic death of drug-resistant cancer cells. Our study provides new insights into the clinical use of USP24 inhibitors as ferroptosis inducers (FINs) to block drug resistance during chemotherapy., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Knowing the remission duration after biologics discontinuation in patients with psoriasis is important, especially when disease relapse is defined as the restart of systemic agents, because it also reflects the real-world clinical practice when topical treatment alone is not adequate for disease control, and a systemic treatment, including biologic, is needed. Biologics are currently indicated for patients with psoriasis who are candidates for systemic treatments., Methods: We included 42 patients who were followed up with regularly after the end of risankizumab, guselkumab and mirikizumab trials and investigated the drug-free remission (DFR). A Kaplan-Meier survival analysis and Cox regression model were employed to identify the possible risk factors for relapse., Results: Overall, 38/42 (90.5%) patients experienced relapses after discontinuing trial biologics during the follow-up period of at least 96 weeks and up to 227 weeks. In all patients with relapse, the median DFR was 104 days. Kaplan-Meier survival analysis revealed a significant 1-year drug-free survival (DFS) difference between risankizumab (Z) and guselkumab (T) + mirikizumab (M) (p = 0.0462). A difference in DFS curves was noted when patients were categorized by disease duration > or ≤ 2 years (p = 0.1577) and maintenance of a psoriasis area and severity index score (PASI) of 90 at the end of trials (p = 0.1177). Univariate Cox regression model identified that age [hazard ratio (HR) = 1.030 (1.000-1.060), p = 0.0467] and disease duration [HR = 1.046(1.009-1.084), p = 0.0134] were significantly associated with relapse risk. A risk model was established on the basis of multivariable Cox regression results. Risk value = 0.021038 * Age + 0.515628 * Biologic&#95;type (Z = 0,T/M = 1) + 0.025048 * Disease&#95;Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) = 0.82-3.23, p = 0.1809]., Conclusion: Types of biologics used, disease duration > or ≤ 2 years, and PASI 90 improvement at the end of trial affect the 1-year DFS after biologics discontinuation. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings., Trial Registration: ClinicalTrials.gov identifiers NCT02694523, NCT03047395, NCT02207224, NCT02576431, NCT03482011, and NCT03556202., (© 2024. The Author(s).)

In this study, we conducted tests on the seeds from four Taiwanese native Camellia species ( C. japonica , C. furfuracea , C. laufoshanensis , and C. formosensis ) and three commercialized species ( C. oleifera , C. brevistyla , and C. sinensis ) for comparison. We examined various aspects of these species, such as seed oil content, suitability for mechanical pressing, volatile components (edible flavor), and oil stability (suitability for cooking), to assess the feasibility of using these four native Taiwanese Camellia seeds as sources of edible oil. The results from solvent extraction tests and mechanical pressing experiments confirm that the seeds from C. furfuracea , C. japonica , and C. laufoshanensis have high oil contents, and their oils are suitable for extraction via the popular mechanical pressing method, with oil yields comparable to or higher than those of the commercialized Camellia species. The volatile components of the oils were collected using MonoTrap adsorbents and analyzed with a thermal desorption system coupled with gas chromatography-mass spectrometry (ATD-GC/MS), primarily consisting of alcohols, ketones, and aldehydes. The results of oxidative stability tests reveal that the seed oils from C. japonica , C. furfuracea , and C. laufoshanensis are higher than or equally stable to those from the commercialized Camellia species. After six months of storage, the stability of these three Camellia seed oils remained relatively high, demonstrating that the seed oils from C. japonica , C. furfuracea , and C. laufoshanensis can withstand high temperatures and can be easily preserved for future applications.

Background: Severe asthma, characterized by inflammation and airway remodeling, involves fibroblast differentiation into myofibroblasts expressing α-SMA. This process leads to the production of fibronectin and connective tissue growth factor (CTGF), driven by factors such as transforming growth factor (TGF)-β. Furthermore, the persistent presence of myofibroblasts is associated with resistance to apoptosis and mitochondrial dysfunction. The chemokine (C-X3-C motif) ligand 1 (CX3CL1) plays a role in tissue fibrosis. However, it is currently unknown whether neutralization of CX3CL1 decreases TGF-β-induced fibroblast differentiation and mitochondrial dysfunction in normal human lung fibroblasts (NHLFs)., Methods: CX3CL1/C-X3-C motif chemokine receptor 1 (CX3CR1), CX3CL1 was analyzed by immunofluorescence (IF) or immunohistochemical (IHC) staining of ovalbumin-challenged mice. CX3CL1 release was detected by ELISA. TGF-β-induced CTGF, fibronectin, and α-SMA expression were evaluated in NHLFs following neutralization of CX3CL1 (TP213) treatment for the indicated times by Western blotting or IF staining. Mitochondrion function was detected by a JC-1 assay and seahorse assay. Cell apoptosis was observed by a terminal uridine nick-end labeling (TUNEL) assay., Results: An increase in CX3CL1 expression was observed in lung tissues from mice with ovalbumin-induced asthma by IF staining. CX3CR1 was increased in the subepithelial layer of the airway by IHC staining. Moreover, CX3CR1 small interfering (si)RNA downregulated TGF-β-induced CTGF and fibronectin expression in NHLFs. CX3CL1 induced CTGF and fibronectin expression in NHLFs. TGF-β-induced CX3CL1 secretion from NHLFs. Furthermore, TP213 decreased TGF-β-induced CTGF, fibronectin, and α-SMA expression in NHLFs. Mitochondrion-related differentially expressed genes (DEGs) were examined after CX3CL1 neutralization in TGF-β-treated NHLFs. TP213 alleviated TGF-β-induced mitochondrial dysfunction and apoptosis resistance in NHLFs. CX3CL1 induced p65, IκBα, and IKKα phosphorylation in a time-dependent manner. Furthermore, CX3CL1-induced fibronectin expression and JC-1 monomer were decreased by p65 siRNA. TP213 reduced TGF-β-induced p65 and α-SMA expression in NHLFs., Conclusions: These findings suggest that neutralizing CX3CL1 attenuates lung fibroblast activation and mitochondrial dysfunction. Understanding the impacts of CX3CL1 neutralization on fibroblast mitochondrial function could contribute to the development of therapeutic strategies for managing airway remodeling in severe asthma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several studies have suggested that mutation of the interleukin 36 receptor antagonist gene (IL36RN) is related to generalized pustular psoriasis (GPP), and the presence of IL36RN mutation may affect the clinical manifestations and treatment responses. However, genetic testing is not routinely available in clinical practice for the diagnosis of GPP. Previously, GPP patients with acrodermatitis continua of Hallopeau (ACH) were found to have a high percentage of carrying IL36RN mutation. In this study, we reported six patients with pustular psoriasis presenting as diffuse palmoplantar erythema with keratoderma among 60 patients who carried IL36RN mutation. ACH was present in five patients and five patients had acute flare of GPP. This unique presentation may serve as a predictor for IL36RN mutation in patients with pustular psoriasis, similar to ACH., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent.

Cirsium japonicum DC. var. australe Kitam. has been used as an herbal remedy and often involves using the whole plant or roots. However, the bioactivities of different parts of the plant have been far less explored. This study aimed to evaluate the antioxidative ability of methanol extracts from the flowers, leaves, stems, and roots of the Cirsium plant and their possible active components against juglone-induced oxidative stress in the nematode Caenorhabditis elegans . The results showed that the highest dry weight (12.3 g per plant) was observed in leaves, which was followed by stems (8.0 g). The methanol extract yields from the flowers, leaves, and roots were all similar (13.0-13.8%), while the yield from stems was the lowest (8.6%). The analysis of the silymarin contents in the extracts indicated that the flowers, leaves, stems, and roots contained silychristin and taxifolin; however, silydianin was only found in the leaves, stems, and roots. The flower, leaf, and stem extracts, at a concentration of 10 mg/L, significantly reduced juglone-induced oxidative stress in C. elegans , which was potentially due to the presence of silychristin and taxifolin. Overall, C. japonicum DC. var. australe Kitam. contains a significant amount of silymarin and exhibits in vivo antioxidative activity, suggesting that the prospects for the plant in terms of health supplements or as a source of silymarin are promising.

Background: Current intraocular pressure (IOP) measurements based on non-contact tonometry are derived from statistics-driven equations and lack biomechanical significance, which often leads to under-estimation in post-refractive surgery cornea. This study aims to introduce and validate modal analysis-derived intraocular pressure (mIOP) as a novel method generated through Legendre-based modal decomposition of the anterior corneal contour; it provides an accurate and intuitive IOP measurement from an energy-based perspective., Methods: This retrospective study included 680 patients. Healthy participants were divided into reference (n = 385) and validation (n = 142) datasets, and the others underwent either femtosecond-assisted laser in situ keratomileusis (FS-LASIK, n = 58) or transepithelial photorefractive keratectomy (TPRK, n = 55). Corneal curvature of the right eyes was extracted from raw serial cross-sectional images of the cornea generated by Corvis ST, a noncontact tonometer with a high-speed Scheimpflug-camera. Legendre expansion was then applied to the corneal curvature to obtain the modal profiles (i.e., temporal changes of the coefficient for each basis polynomial [modes]). Using the reference dataset, feature selection on the modal profiles generated a final mIOP model consisting of a single parameter: total area under curve (frames 1-140) divided by the area under curve of the rising phase (frames 24-40) in the fourth mode, i.e. the M 4 ratio. Validation was performed in both the healthy validation and postoperative datasets. IOP-Corvis, pachymetry-corrected IOP, biomechanically corrected IOP, and mIOP values were compared. For the FS-LASIK and TPRK groups, pairwise postoperative IOP changes were analyzed through repeated measures analysis of variance, and agreement was examined through Bland-Altman analysis. Using a finite element analysis based three-dimensional model of the human cornea, we further compared the M 4 ratio with the true intraocular pressure within the physiological range., Results: The M 4 ratio-based mIOP demonstrated weak to negligible association with age, radius of corneal curvature, and central corneal thickness (CCT) in all validation analyses, and performed comparably with biomechanically corrected IOP (bIOP) in the refractive surgery groups. Both remained nearly constant postoperatively and were not influenced by CCT changes. Additionally, M 4 ratio accurately represented true intraocular pressure in the in silico model., Conclusions: mIOP is a reliable IOP measurement in healthy and postrefractive surgery populations. This energy-based, ratio-derived approach effectively filters out pathological, rotational, misaligned movements and serves as an interpatient self-calibration index. Modal analysis of corneal deformation dynamics provides novel insights into regional corneal responses against pressure loading., (© 2023. The Author(s).)

Background: Smoke produced by traditional open surgery (TOS) has long been considered hazardous to medical staff. Compared with TOS, minimally invasive surgery under carbon dioxide pneumoperitoneum is associated with a faster recovery and less wound pain. However, the impact of oxygen-deficient environment on the chemical contents of smoke has not been comprehensively assessed., Methods: This research evaluated the chemical composition and volatile organic compound (TVOC) level in smoke produced by open cholecystectomy (OC) versus laparoscopic cholecystectomy (LC) for gallbladder diseases. Smoke samples were collected and analyzed via gas chromatography-mass spectrometry. Chemical compounds were further grouped according to molecular weight and toxicity., Results: Compared with the OC, LC had significantly higher halocarbon and TVOC levels but lower cycloalkene and aldehyde levels. No halocarbons were isolated from OC specimens. When stratified based on molecular weight, LC had a bimodal pattern (i.e., high levels of small-sized [<60 Da] and large-sized [>120 Da] compounds). There was no difference in terms of toxicity types, incidence, and severity associated with detected compounds between two groups., Conclusion: LC is associated with a higher TVOC level and proportion of low- and high-molecular-weight organic compounds. Further strategies of evacuating these health hazards and preventing smoke leakage through trocars should be considered., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Many individuals with stroke experience upper-limb motor deficits, and a recent trend is to develop novel devices for enhancing their motor function. This study aimed to develop a new upper-limb rehabilitation system with the integration of two rehabilitation therapies into one system, digital mirror therapy (MT) and action observation therapy (AOT), and to test the usability of this system. In the part I study, the new system was designed to operate in multiple training modes of digital MT (i.e., unilateral and bilateral modes) and AOT (i.e., pre-recorded and self-recorded videos) with self-developed software. In the part II study, 4 certified occupational therapists and 10 stroke patients were recruited for evaluating usability. The System Usability Scale (SUS) (maximum score = 100) and a self-designed questionnaire (maximum score = 50) were used. The mean scores of the SUS were 79.38 and 80.00, and those of the self-designed questionnaire were 41.00 and 42.80, respectively, for the therapists and patients after using this system, which indicated good usability and user experiences. This novel upper-limb rehabilitation system with good usability might be further used to increase the delivery of two emerging rehabilitation therapies, digital AOT and MT, to individuals with stroke., (© 2022. The Author(s).)

Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.

It is essential to understand the failure modes and the failure moments of curved stems since trees could be damaged and may cause severe loss of life and property in urban. In our previous papers, the cracking failure mechanism of hollow erect and curved trunks under bending moment was clarified and we also found that the mechanism of cracking failure of solid trunk is different from the hollow one. While the existing equation to calculate the transverse stress of a solid curved stem under a bending moment is approximate and may cause considerable errors when the initial curvature of stem is small. To solve this problem, a series of novel equations were derived in this study. Among these newly derived equations, 3 of them are especially practical in the assessment of the risk of urban tree for both safety and environment management which are M c , c min R and c cri R. The equation of M c is to calculate the bending moment for a solid curved trunk at which the cracking failure is initiated and this equation is more accurate than the existing equation. The equation of c min R is to calculate the minimum cR (c: curvature, R: radius of trunk) below which cracking failure will not occur, and the equation of c cri R is to calculate the critical cR which represents equal opportunities for cracking and bending failure of the stem to occur. To exert our model to practice, the equations derived in this paper were applied to literature data (Wood handbook, 1999). From the data of 41 species of softwood and 48 species of hardwood, statistically, hardwoods have larger average values of c min R and c cri R than softwoods which means that hardwoods are more resistant to cracking failure than softwoods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Electrochemical advanced oxidation process (EAOP) is known for its efficient and fast degradation of organic pollutants in polluted water treatment. In this study, the EAOP using a boron-doped diamond (BDD) anode was applied to treat two-season groundwater samples collected from four sampling wells (GS1 to GS4) with petrochemical contaminants including methyl tert-butyl ether (MTBE), benzene, toluene, chlorobenzene, total organic compounds (TOC), and total petroleum hydrocarbons (TPH) at a gas station in southern Taiwan. Moreover, toxicity tests (ATP, p53, and NF-κB bioassays) were performed to evaluate the biological responses of raw and EAOP-treated groundwater. Results show that the concentrations of chlorobenzene before and after EAOP treatment were all below its method detection limit. High degradation efficiencies were observed for MTBE (100%), benzene (100%), toluene (100%, except that of GS2 in the first season), TPH (94-97%, except that of GS4 in the first season), and TOC (85-99%). Cell viability for both the raw groundwater (81.2 ± 13.5%) and EAOP-treated samples (84.7 ± 11.7%) as detected using the ATP bioassay showed no significant difference (p = 0.715). A mean reduction in the DNA damage (739 to 165 ng DOX-equivalency L -1 (ng DOX-EQ. L -1 )) and inflammatory response levels (460 to 157 ng TNFα-equivalency L -1 (ng TNFα-EQ. L -1 )) were observed for EAOP-treated samples subjected to p53 and NF-κB bioassays. Overall, the significances of the average degradation efficiency, DNA damage, and inflammatory response before and after groundwater with EAOP treatment was observed to be significant (p < 0.05). p53 and NF-κB bioassays might be applied to assess ecotoxic risk in the environment.

Understanding the failure modes of curved hollow tree trunks is essential from both safety and conservation perspectives. Despite extensive research, the underlying mechanism that determines the cracking failure of curved hollow tree trunks remains unclear due to the lack of theoretical analysis that considers both the initial curvature and orthotropic material properties. Here we derive new mathematical expressions for predicting the bending moment, M crack , at which the cracking failure occurs. The failure mode of a tree species is then determined, as a function of t / R and cR , by comparing M crack with M bend , where t , R and c are, respectively, the trunk wall thickness, outer radius and initial curvature; M bend is the bending moment for conventional bending failure. Our equation shows that M crack is proportional to the tangential tensile strength of wood σ T , increases with t / R , and decreases with the final cR . We analyse 11 tree species and find that hardwoods are more likely to fail in conventional bending, whereas softwoods tend to break due to cracking. This is due to the softwoods' much smaller tangential tensile strength, as observed from the data of 66 hardwoods and 43 softwoods. For larger cR , cracking failure is easier to occur in curvature-decreasing bending than curvature-increasing due to additional normal tensile force F acting on the neutral cross-section; on the other hand, for smaller cR , bending failure is easier to occur due to decreased final curvature. Our formulae are applicable to other natural and man-made curved hollow beams with orthotropic material properties. Our findings provide insights for those managing trees in urban situations and those managing for conservation of hollow-dependent fauna in both urban and rural settings., Competing Interests: We declare we have no competing interests., (© 2020 The Authors.)

Camellia brevistyla (Hayata) Coh. Stuart seeds are used to produce edible oil. The seed pomace is an agricultural waste, containing approximately 8% saponin, which has antihypertensive effects. N ω -nitro-L-arginine methyl ester (L-NAME) can induce hypertension with no deficiency on mice. Here, we investigated the effects of ethanol extract from C. brevistyla seed pomace (CBPE) in L-NAME-induced hypertension mice. The results showed that all doses of CBPE significantly decreased systolic (117 ± 5-122 ± 5 mmHg) and diastolic (72 ± 16-77 ± 8 mmHg) blood pressure, aortic intima media thickness (48 ± 5-53 ± 5 µm), and also reduced the MDA adduct and protein carbonyl levels in the liver (101 ± 19-114 ± 17 ρmol/mL and 4.8 - 5.2 nmol/mg) compared to those observed in the L-NAME group (140 ± 3 and 95 ± 8 mmHg, 65 ± 10 µm, 145 ± 25 ρmol/mL, and 7.8 nmol/mg; P < 0.05). These results suggest that CBPE has profitable antihypertensive properties which are preventing aorta remodeling and reducing liver oxidative stress in hypertensive mice., (© 2019 Institute of Food Technologists®.)

Carfentanil is a synthetic opioid significantly more potent than clinically prescribed fentanyl. The primary metabolites of carfentanil, generated from human liver microsomes, were structurally confirmed through chemical synthesis. The synthesized compounds were evaluated for μ-opioid receptor (MOR) functional activity. Of the six metabolites assayed, a major metabolite showed comparable activity to the parent opioid. Three other metabolites showed significant MOR functional activity. The availability of the metabolites could aid improvements in the analysis of biomedical samples obtained from suspected human exposures to carfentanil and development of treatment protocols., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay., Competing Interests: The authors declare no competing financial interest.

Scope: Selenium is an important nutrient for human health. The influence of dietary selenium on lipid metabolism remains largely unknown. N-γ-(l-glutamyl)-l-selenomethionine (Glu-SeMet) on inhibition of fat accumulation and its underlying mechanisms in the nematode Caenorhabditis elegans are investigated., Methods and Results: Triacylglyceride quantification and post-fixed Nile red staining methods are conducted to evaluate fat accumulation in wild-type N2 worms in normal or high-glucose diet. Glu-SeMet (0.01 µm) treatment effectively reduces fat storage in wild-type N2 C. elegans in both a normal and high-glucose diet. Further evidence shows that Glu-SeMet (0.01 µm) decreases the ratio of oleic acid/stearic acid (C18:1Δ9/C18:0) using gas chromatography-mass spectrometry analysis. The mRNA levels of fatty acid stearoyl-CoA desaturases, FAT-6 and FAT-7, and the mediator-15 (MDT-15) are downregulated while the wild-type N2 worms are co-treated with high glucose and Glu-SeMet (0.01 µm). The effect of reduced fat accumulation is absent in fat-6, fat-7, and trxr-1 mutant worms under high glucose and Glu-SeMet (0.01 µm) co-treatment., Conclusions: This study demonstrates that Glu-SeMet inhibiting fat accumulation may be associated with FAT-6 and FAT-7 and the selenoprotein TRXR-1 in C. elegans. This study implies a potential for Glu-SeMet as a new treatment for obesity or its complications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The xanthine oxidase inhibitory activity and thermostability of Cinnamomum osmophloeum leaf oil microencapsulated with β-cyclodextrin were evaluated in this study. The yield of leaf oil microcapsules was 86.3% using the optimal reaction conditions at the leaf oil to β-cyclodextrin ratio of 15:85 and ethanol to water ratio ranging from 1:3 to 1:5. Based on the FTIR analysis, the characteristic absorption bands of major constituent, trans -cinnamaldehyde, were confirmed in the spectra of leaf oil microcapsules. According to the dry-heat aging test, β-cyclodextrin was thermostable under the high temperature conditions, and it was beneficial to reduce the emission of C. osmophloeum leaf oil. Leaf oil microcapsules exhibited high xanthine oxidase inhibitory activity, with an IC 50 value of 83.3 µg/mL. It is concluded that the lifetime of C. osmophloeum leaf oil can be effectively improved by microencapsulation, and leaf oil microcapsules possess superior xanthine oxidase inhibitory activity.

In this study, the effects of roasting camellia (Camellia oleifera Abel.) seed oils at different temperatures (65°C, 100°C, 120°C, and 140°C) on the oxidative stability and composition of the oils were investigated. The results showed that, in terms of the quality of the oils, the roasting temperature influenced the total phenolic content (which ranged from 1.64～2.45 GAE mg/g for the different oils) and total flavonoid content (which ranged from 0.36～0.45 QE mg/g for the different oils), while the fatty acid profile and tocopherol content were not influenced by the roasting temperature. We also investigated the kinetic parameters of camellia seed oil during oxidation via Rancimat (at temperatures ranging from 110~140°C). It turned out that the natural logarithms of the oxidative stability index (OSI) varied linearly with respect to temperature (R 2 : 0.958～0.997). This was done on the basis of the Arrhenius equation that indicates that the activation energies (Ea) for oxidative stability are 65.7～78.4 KJ/mol. Simultaneously, we found that increasing the roasting temperature could increase the antioxidant stability of Maillard reaction products in camellia seed oil. The effects of roasting include the assurance that the camellia seed oil so produced will comply with the relevant governmental health codes and standards and have a longer shelf life.

Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects. These are important for establishing a comprehensive understanding of the toxic mechanisms of OP nerve agents. To identify novel proteins that interact with VX, and that may give insight into these other mechanisms, we used activity-based protein profiling (ABPP) employing a novel VX-probe on lysates from rat heart, liver, kidney, diaphragm, and brain tissue. By making use of a biotin linked VX-probe, proteins covalently bound by the probe were isolated and enriched using streptavidin beads. The proteins were then digested, labeled with isobarically distinct tandem mass tag (TMT) labels, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative analysis identified 132 bound proteins, with many proteins found in multiple tissues. As with previously published ABPP OP work, monoacylglycerol lipase associated proteins and fatty acid amide hydrolase (FAAH) were shown to be targets of VX. In addition to these two and other predicted neurotransmitter-related proteins, a number of proteins involved with energy metabolism were identified. Four of these enzymes, mitochondrial isocitrate dehydrogenase 2 (IDH2), isocitrate dehydrogenase 3 (IDH3), malate dehydrogenase (MDH), and succinyl CoA (SCS) ligase, were assayed for VX inhibition. Only IDH2 NADP+ activity was shown to be inhibited directly. This result is consistent with other work reporting animals exposed to OP compounds exhibit reduced IDH activity. Though clearly a secondary mechanism for toxicity, this is the first time VX has been shown to directly interfere with energy metabolism. Taken together, the ABPP work described here suggests the discovery of novel protein-agent interactions, which could be useful for the development of novel diagnostics or potential adjuvant therapeutics.

Failure of hollow trees in urban areas is a worldwide concern, and it can be caused by different mechanisms, i.e. bending stresses or flattening-related failures. Here we derive a new analytical expression for predicting the bending moment for tangential cracking, and compare the breaking moment of various failure modes, including Brazier buckling, tangential cracking, shear failure and conventional bending failure, as a function of t / R ratio, where t and R are the trunk wall thickness and trunk radius, respectively, of a hollow tree. We use Taiwan red cypress as an example and show that its failure modes and the corresponding t / R ratios are: Brazier buckling (Mode I), tangential cracking followed by longitudinal splitting (Mode II) and conventional bending failure (Mode III) for 0 <  t / R  < 0.06, 0.06 <  t / R  < 0.27 and 0.27 <  t / R  < 1, respectively. The exact values of those ratios may vary within and among species, but the variation is much smaller than individual mechanical properties. Also, shear failure, another type of cracking due to maximum shear stress near the neutral axis of the tree trunk, is unlikely to occur since it requires much larger bending moments. Hence, we conclude that tangential cracking due to cross-sectional flattening, followed by longitudinal splitting, is dominant for hollow trunks. Our equations are applicable to analyse straight hollow tree trunks and plant stems, but are not applicable to those with side openings or those with only heart decay. Our findings provide insights for those managing trees in urban situations and those managing for conservation of hollow-dependent fauna in both urban and rural settings., Competing Interests: We have no competing interests.

Background: Longan is a fruit tree known to contain many phenolic components, which are capable of protecting people from oxidative damage through an anti-inflammatory mechanism. It may be also worthwhile to study the effect on lowering uric acid activity., Materials and Methods: This study investigates the lowering of uric acid using longan extracts, including flowers, pericarps, seeds, leaves, and twigs, on potassium-oxonate-induced hyperuricemia mice and its inhibitory actions against xanthine oxidase (XO) activities., Results: The findings revealed that ethyl acetate fraction of longan extracts exhibited strong XO-inhibitory activity, and the flower extracts (IC50 = 115.8 μg/mL) revealed more potent XO-inhibitory activity to those of pericarps (118.9 μg/mL), twigs (125.3 μg/mL), seeds (262.5 μg/mL), and leaves (331.1 μg/mL) in vitro. In addition, different dosages of longan extract (50-100 mg/kg) were administered to hyperuricemic mice. The lowering effect of longan extracts on uric acid at 75 mg/kg markedly reduced plasma uric acid levels in decreasing order: Flowers (80%) > seeds (72%) > pericarps (64%) > twigs (59%) > leaves (41%), compared with allopurinol (89%). Finally, 10 isolated phytochemicals from longan flowers were then examined in vitro. The results indicated that proanthocyanidin A2 and acetonylgeraniin A significantly inhibited XO activity in vitro. This is the first report providing new insights into the urate-reducing effect of phenolic dimer and hydrolyzable tannin, which can be developed to potential hypouricemic agents., Summary: Longan flower extracts possess more potent XO-inhibitory activity than pericarps, twigs, seeds, and leaves in vitroThe lowering effect of longan flowers and seeds extracts markedly reduced plasma uric acid levels as compared to allopurinol in vivoThe extract proanthocyanidin A2 and acetonylgeraniin A were demonstrated potent XO inhibitory activity in vitro Abbreviations used: PO: Potassium-oxonate, XO: xanthine oxidase, HE: n-hexane, EA: ethyl acetate, i.p.: intraperitoneal, PBS: phosphate-buffered saline, AP: allopurinol, PUA: plasma uric acid.

Arsenic (As) is a human carcinogen, and arsenic contamination in groundwater is a worldwide public health concern. Arsenic-affected areas are found in many places but are reported mostly in agricultural farmlands, yet the interaction of fertilizers, microorganisms, and arsenic mobilization in arsenic-contaminated aquifers remains uncharacterized. This study investigates the effects of fertilizers and bacteria on the mobilization of arsenic in two arsenic-contaminated aquifers. We performed microcosm experiments using arsenic-contaminated sediments and amended with inorganic nitrogenous or phosphorus fertilizers for 1 and 4 months under aerobic and anaerobic conditions. The results show that microcosms amended with 100 mg/L phosphorus fertilizers (dipotassium phosphate), but not nitrogenous fertilizers (ammonium sulfate), significantly increase aqueous As(III) release in arsenic-contaminated sediments under anaerobic condition. We also show that concentrations of iron, manganese, potassium, sodium, calcium, and magnesium are increased in the aqueous phase and that the addition of dipotassium phosphate causes a further increase in aqueous iron, potassium, and sodium, suggesting that multiple metal elements may take part in the arsenic release process. Furthermore, microbial analysis indicates that the dominant microbial phylum is shifted from α-proteobacteria to β- and γ-proteobacteria when the As(III) is increased and phosphate is added in the aquifer. Our results provide evidence that both phosphorus fertilizers and microorganisms can mediate the release of arsenic to groundwater in arsenic-contaminated sediments under anaerobic condition. Our study suggests that agricultural activity such as the use of fertilizers and monitoring phosphate concentration in groundwater should be taken into consideration for the management of arsenic in groundwater.

Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2'-O-β-d-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver-Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics.

Pterosins are abundant in ferns, and pterosin A was considered a novel activator of adenosine monophosphate-activated protein kinase, which is crucial for regulating blood glucose homeostasis. However, the distribution of pterosins in different species of ferns from various places in Taiwan is currently unclear. To address this question, the distribution of pterosins, glucose-uptake efficiency, and protective effects of pterosin A on β-cells were examined. Our results showed that three novel compounds, 13-chloro-spelosin 3-O-β-d-glucopyranoside (1), (3R)-Pterosin D 3-O-β-d-(3'-p-coumaroyl)-glucopyranoside (2), and (2R,3R)-Pterosin L 3-O-β-d-(3'-p-coumaroyl)-glucopyranoside (3), were isolated for the first time from four fern species (Ceratopteris thalictroides, Hypolepis punctata, Nephrolepis multiflora, and Pteridium revolutum) along with 27 known compounds. We also examined the distribution of these pterosin compounds in the mentioned fern species (except N. multiflora). Although all pterosin analogs exhibited the same effects in glucose uptake assays, pterosin A prevented cell death and reduced reactive oxygen species (ROS) production. This paper is the first report to provide new insights into the distribution of pterosins in ferns from Taiwan. The potential anti-diabetic activity of these novel phytocompounds warrants further functional studies.

Ferruginol has antifungal activity against wood-rot fungi (basidiomycetes). However, specific research on the antifungal mechanisms of ferruginol is scarce. Two-dimensional gel electrophoresis and fluorescent image analysis were employed to evaluate the differential protein expression of wood-rot fungus Trametes versicolor treated with or without ferruginol. Results from protein identification of tryptic peptides via liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) analyses revealed 17 protein assignments with differential expression. Downregulation of cytoskeleton β-tubulin 3 indicates that ferruginol has potential to be used as a microtubule-disrupting agent. Downregulation of major facilitator superfamily (MFS)–multiple drug resistance (MDR) transporter and peroxiredoxin TSA1 were observed, suggesting reduction in self-defensive capabilities of T. versicolor. In addition, the proteins involved in polypeptide sorting and DNA repair were also downregulated, while heat shock proteins and autophagy-related protein 7 were upregulated. These observations reveal that such cellular dysfunction and damage caused by ferruginol lead to growth inhibition and autophagic cell death of fungi.

Five new 5β,19-epoxycucurbitane triterpenoids, taikugausins A-E (1-5), together with 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (6), have been isolated and characterized from the 70 % EtOH extract of the fresh fruits of Momordica charantia. The chemical structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analyses, especially 2D NMR (HMQC, HMBC, and NOESY) experiments and HRESIMS data. The relationship between NMR chemical shifts and the configuration of C-19 with an OMe group in 5β,19-epoxycucurbitane are described. Among them, compounds 3 and 4 exhibited remarkable anti-inflammatory activities by the inhibition of nitric oxide production at the concentration of 10 µg/mL. In addition, 3 and 4 also showed moderate cytotoxicity against WiDr, Hep G2, MCF-7, and HEp-2 human tumor cell lines., (Georg Thieme Verlag KG Stuttgart · New York.)

Clinical studies show that hyperuricemia is a risk factor in the progression and development of cardiovascular and metabolic disease. Elevated serum levels of uric acid induce renal injury via an inflammation response, but the detailed mechanism is still under study. To better understand the effect of hyperuricemia on the kidney, we used gas chromatography-mass spectrometry-based metabolomics to investigate the role of uric acid in the mouse kidney. Partial least-squares discriminant analysis revealed significant differences between control and hyperuricemia groups in urine metabolic profiles. We identified 33 metabolites from 76 highly reproducible peaks and found abnormal uric acid levels related to comprehensive kidney injury, including excretive function and energy metabolism. Additionally, inflammation induced by the interleukin 6/signal transducer and activator of transcription 3 signaling pathway participated in hyperuricemia-induced kidney injury. This study helps understand the relationship between hyperuricemia and kidney injury. Metabolomics may be a useful strategy for early diagnosis of kidney damage., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

There is a growing interest in the exploitation of the residues generated by plants. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace, produced when tea seed is processed. DPPH radical scavenging and total phenolic content assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as in vivo model to evaluate the beneficial health effects, including antioxidant activity, delayed aging, and reduced amyloid-β toxicity. Among all soluble fractions obtained from the extracts of tea seed pomace from Camellia tenuifolia, the methanol (MeOH)-soluble fraction has the best in vivo antioxidant activities. The MeOH-soluble extraction was further divided into six fractions by chromatography with a Diaion HP-20 column eluted with water/MeOH, and fraction 3 showed the best in vitro and in vivo antioxidant activities. Further analysis in C. elegans showed that the MeOH extract (fraction 3) of tea seed pomace significantly decreased intracellular reactive oxygen species, prolonged C. elegans lifespan, and reduced amyloid-β (Aβ) toxicity in transgenic C. elegans expressing human Aβ. Moreover, bioactivity-guided fractionation yielded two potent constituents from fraction 3 of the MeOH extract, namely, kaempferol 3-O-(2″-glucopyranosyl)-rutinoside and kaempferol 3-O-(2″-xylopyranosyl)-rutinoside, and both compounds exhibited excellent in vivo antioxidant activity. Taken together, MeOH extracts of tea seed pomace from C. tenuifolia have multiple beneficial health effects, suggesting that biowaste might be valuable to be explored for further development as nutraceutical products. Furthermore, the reuse of agricultural byproduct tea seed pomace also fulfills the environmental perspective.

Cinnamomum osmophloeum Kaneh. is an indigenous tree species in Taiwan. The present study investigates phytochemical characteristics, antioxidant activities, and longevity of the essential oils from the leaves of the mixed-type C. osmophloeum tree. We demonstrate that the essential oils from leaves of mixed-type C. osmophloeum exerted in vivo antioxidant activities on Caenorhabditis elegans. In addition, minor (alloaromadendrene, 5.0%) but not major chemical components from the leaves of mixed-type C. osmophloeum have a key role against juglone-induced oxidative stress in C. elegans. Additionally, alloaromadendrene not only acts protective against oxidative stress but also prolongs the lifespan of C. elegans. Moreover, mechanistic studies show that DAF-16 is required for alloaromadendrene-mediated oxidative stress resistance and longevity in C. elegans. The results in the present study indicate that the leaves of mixed-type C. osmophloeum and essential oil alloaromadendrene have the potential for use as a source for antioxidants or treatments to delay aging.

Abnormal serum urate levels are recognized as a critical factor in the progression of several chronic diseases. To evaluate the antihyperuricemic effect of Davallia formosana, the inhibitory activities of 15 isolated phytochemicals, including five novel compounds of 6,8-dihydroxychromone-7-C- β -d-glucopyranoside (1), 6,8,3',4'-tetrahydroxyflavanone-7-C- β -d-glucopyranoside (2), 6,8,4'-trihydroxyflavanone-7-C- β -d-glucopyranoside (3), 8-(2-pyrrolidinone-5-yl)-catechin-3-O- β -d-allopyranoside (4), and epiphyllocoumarin-3-O- β -d-allopyranoside (5), were examined against xanthine oxidase (XOD) and in a potassium oxonate-(PTO-) induced acute hyperuricemic mice model. The results indicated that compounds 3 and 5 significantly inhibited XOD activity in vitro and reduced serum uric acid levels in vivo. This is the first report providing new insights into the antihyperuricemic activities of flavonoid glycosides which can possibly be developed into potential hypouricemic agents.

Arsenic (As) contamination of groundwater is a significant public health concern. In this study, the removal of arsenic from groundwater using biological processes was investigated. The efficiency of arsenite (As(III)) bacterial oxidation and subsequent arsenate (As(V)) removal from contaminated groundwater using bacterial biomass was examined. A novel As(III)-oxidizing bacterium (As7325) was isolated from the aquifer in the blackfoot disease (BFD) endemic area in Taiwan. As7325 oxidized 2300μg/l As(III) using in situ As(III)-contaminated groundwater under aerobic conditions within 1d. After the oxidation of As(III) to As(V), As(V) removal was further examined using As7325 cell pellets. The results showed that As(V) could be adsorbed efficiently by lyophilized As7325 cell pellets, the efficiency of which was related to lyophilized cell pellet concentration. Our study conducted the examination of an alternative technology for the removal of As(III) and As(V) from groundwater, indicating that the oxidation of As(III)-contaminated groundwater by native isolated bacterium, followed by As(V) removal using bacterial biomass is a potentially effective technology for the treatment of As(III)-contaminated groundwater., (© 2013.)

Objectives: This study describes a novel carrier, the ethosome-based system, which is composed of non-ionic surfactants, ethanol, and water., Methods: Brij(®) 52 (non-ionic surfactants), soya phosphatidylcholine (PC), cholesterol, and the major compounds (caffeine and gallic acid) of black tea extracts were dissolved in the ethanolic phase. The aqueous phase containing Paragon III was heated to 60 °C and mixed with the previous solution. Finally, 3.4 ml NaOH (6.5 N) was added to adjust the pH level to 4.05. The mixture was centrifuged at 2000 g for two minutes, and the precipitate was taken as the end product. Black tea extracts were applied in ethosome-based formulations, and the efficacy of these formulations in penetrating nude mouse skin and in dyeing white hairs was investigated., Results: Compared with an ethanolic solution and black tea extracts, the non-ionic ethosomal delivery system dramatically enhanced the adsorption of black tea extracts onto hair surfaces in vitro. The non-ionic ethosomal system was much more efficient in delivering and facilitating the adsorption of black tea extracts to the hair surface than hydroalcoholic black tea extracts., Conclusions: This formulation may have potential for development as a hair dye and protective agent., (© 2013 The International Society of Dermatology.)

This paper reports that bioassay-guided fractionations of EtOH extract of Momordica charantia fruits led to the isolation of 15 cucurbitane-type triterpene glycosides including 4 new compounds, kuguaosides A-D (1-4), along with 11 known ones, charantoside A (5), momordicosides I (6), F1 (7), F2 (8), K (9), L (10), and U (11), goyaglycosides-b (12) and -d (13), 7β,25-dihydroxycucurbita-5,23(E)-dien-19-al 3-O-β-d-allopyranoside (14), and 25-hydroxy-5β,19-epoxycucurbita-6,23-dien-19-on-3β-ol 3-O-β-d-glucopyranoside (15). Their structures were elucidated on the basis of spectroscopic analyses and chemical methods. This study also established the HPLC-ELSD fingerprinting profile of an antiproliferative fraction of which 11 main peaks were identified. Biological evaluation showed that several isolated cucurbitane-type triterpene glycosides had antiproliferative activities against MCF-7, WiDr, HEp-2, and Doay human tumor cell lines. In addition, compound 14 showed potent hypoglycemic activities by glucose uptake assay.

Objectives: The primary objective of this study was to investigate the feasibility of using niosomes as a delivery vehicle for the dermal administration in vitro of black tea extract (BTE) as a sunscreen., Methods: Multi-lamellar niosomes were obtained by means of a previously reported method of lipid hydration films. In vitro penetration experiments through nude mouse skin were carried out to evaluate the potential of niosomes as a dermal formulation. The nude mouse skin membrane allowed the effects of penetration with a niosome formulation to be evaluated. Penetration rates of caffeine- and gallic acid-loaded niosomes in a steady state were higher than dispersion in aqueous solutions., Results: For skin permeation, higher transdermal absorption rates were seen with solutions of caffeine and gallic acid., Conclusions: In the near future, BTE as a sunscreen agent will be dermally delivered by niosomes., (© 2012 The International Society of Dermatology.)

The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet-fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.

Background. Traditional Chinese medicine (TCM), when given as a therapy for symptom relief, has gained widespread popularity among diabetic patients. The aim of this study is to analyze the utilization of TCM among type 2 diabetic patients in Taiwan. Methods. The use of TCM for type 2 diabetic patients were evaluated using a randomly sampled cohort of 1,000,000 beneficiaries recruited from the National Health Insurance Research Database. Results. Overall, 77.9% (n = 31,289) of type 2 diabetic patients utilized TCM and 13.9% (n = 4,351) of them used TCM for the treatment of type 2 diabetes. Among the top ten most frequently prescribed herbal formulae, four remedies, Zhi-Bo-Di-Huang-Wan, Qi-Ju-Di-Huang-Wan, Ji-Sheng-Shen-Qi-Wan and Ba-Wei-Di-Huang-Wan are derivative formulae of Liu-Wei-Di-Huang-Wan. In other words, Liu-Wei-Di-Huang-Wan and its derivatives were found to be the most common herbal formulae prescribed by TCM doctors for the treatment of diabetes in Taiwan. Conclusion. Although some evidence does support the use TCM to treat diabetes, the results from the current study may have been confounded by placebo effect, which emphasize the need for well conducted, double-blind, randomized, placebo-controlled studies in order to further evaluate the efficacy of Liu-Wei-Di-Huang-Wan on patients with type 2 diabetes.

The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (±)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ∼71% 1 was excreted as metabolites in rat urine.

Microbiota in the gut are considered an important environmental factor associated with host metabolism and physiology. Although gut microbiota are known to contribute to hepatic lipogenesis and fat storage, little is known about how the condition influences the deposition of glycogen in the liver. To better understand and characterize the host energy metabolism in guts lacking microbiota, we compared the liver metabolome of specific pathogen-free and germ-free mice by gas chromatography-mass spectrometry combined with partial least-squares discriminant analysis. We identified 30 of 52 highly reproducible peaks in chromatograms of liver tissue extracts from the two groups of mice. The two groups showed significant differences in metabolic profile. Changes in liver metabolism involved metabolites such as amino acids, fatty acids, organic acids and carbohydrates. The metabolic profile of germ-free mice suggests that they synthesize glycogen and accumulate it in the liver through gluconeogenesis and glycogenesis. Our findings shed light on a new perspective of the role of gut microbiota in energy metabolism and will be useful to help study probiotics, obesity and metabolic diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cinnamomum osmophloeum Kaneh is an indigenous tree species in Taiwan. In this study, phytochemical characteristics and antioxidant activities of the essential oils and key constituents from the leaves of two C. osmophloeum clones were investigated. The two trees possess two chemotypes, which were classified as the cinnamaldehyde type and camphor type. We demonstrated that the essential oils from C. osmophloeum leaves exerted in vivo antioxidant activities in Caenorhabditis elegans. In addition, trans-cinnamaldehyde and D-(+)-camphor, which respectively represent the major compounds in the cinnamaldehyde-type and camphor-type trees, exerted significant in vivo antioxidant activities against juglone-induced oxidative stress in C. elegans. Moreover, expressions of antioxidative-related genes, including superoxide dismutase (SOD) and glutathione S-transferase (GST), were significantly induced by trans-cinnamaldehyde and D-(+)-camphor from C. osmophloeum leaves. Our results showed that the essential oils from C. osmophloeum leaves and their major compounds might have good potential for further development as nutraceuticals or antioxidant remedies.

1. Tanshinone IIA, one of the active components of the Radix of Salvia miltiorrhiza, is used in traditional Chinese medicine to treat cardiovascular diseases. However, the intracellular mechanism of action of tanshinone IIA remain to be determined. The aims of the present study were to test the hypothesis that tanshinone IIA alters strain-induced endothelin (ET)-1 expression and nitric oxide (NO) production, as well as to identify the putative signalling pathways involved, in human umbilical vein endothelial cells (HUVEC). 2. Cultured HUVEC were exposed to cyclic strain in the presence of 1-10 μmol/L tanshinone IIA. Expression of ET-1 was examined by reverse transcription-polymerase chain reaction and ELISA. Phosphorylation of endothelial NO synthase (eNOS) and activating transcription factor (ATF) 3 was assessed by western blot analysis. 3. Tanshinone IIA (3 and 10 μmol/L) inhibited strain-induced ET-1 expression. In contrast, NO production, eNOS phosphorylation and ATF3 expression were enhanced by tanshinone IIA. The eNOS inhibitor N(G) -nitro-L-arginine methyl ester (l-NAME; 100 μmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (5 μmol/L) and the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; 10 μmol/L) inhibited tanshinone IIA-induced increases in ATF3 expression. Moreover, treatment of HUVEC with either an NO donor (3,3-bis [aminoethyl]-1-hydroxy-2-oxo-1-triazene; 500 μmol/L) or an ATF3 activator (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal; 5 μmol/L) resulted in the repression of strain-induced ET-1 expression. The inhibitory effect of tanshinone IIA on strain-induced ET-1 expression was significantly attenuated by l-NAME, ODQ and the transfection of small interfering RNA for ATF3. 4. In conclusion, tanshinone IIA inhibits strain-induced ET-1 expression by increasing NO and upregulating ATF3 in HUVEC. The present study provides important new insights into the molecular pathways that may contribute to the beneficial effects of tanshinone IIA in the cardiovascular system., (© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.)

Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-d-glucoside (3), methyl 6-O-galloyl-β-d-glucoside (4), methyl 3,6-di-O-galloyl-α-d-glucopyranoside (5), gentisic acid 5-O-α-d-(6'-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-β-d-(6'-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-β-d-(6'-O-galloyl) glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases.

Corni fructus is the fruit of Cornus officinalis Sieb. et Zucc. and has attracted much interest due to its traditional applications and active fraction that reportedly possesses antidiabetic effects. In this study, we isolated 12 compounds from Corni fructus including three flavonoids, two iridoid glycosides, three phenolic compounds, and two triterpenoids, together with cornuside (11) and 2-butoxybutanedioic acid (12). Chemical structures were identified by (1)H, (13)C NMR, DEPT, COSY, HSQC, and HMBC spectral analyses. Furthermore, the glucose uptake efficiency, messenger (m)RNA expression of phosphoenolpyruvate carboxykinase (PEPCK), and prevention of cytokine-mediated cytotoxicity in the presence of test agents were evaluated. While CH and CB significantly increased glucose uptake from muscle, compounds 3 and 8, each at 50 μM, significantly suppressed PEPCK mRNA expression. Finally, compound 5, at 50 and 100 μM, effectively attenuated β-cell death. In conclusion, those compounds could contribute to the antihyperglycemic and β-cell-protective actions of Corni fructus against diabetes mellitus.

From the screening of 21 microbial strains, Absidia pseudocylindrospora ATCC 24169 and Aspergillus niger BCRC 32720 were found to reproducibly transform isosteviol lactam (4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam) (3) into various compounds. Preparative-scale transformation of 3 with Abs. pseudocylindrospora yielded two new hydroxylated compounds (4 and 5), with conservation of the lactam ring. Preparative-scale transformation of 3 with Asp. niger afforded seven new compounds, 6 and 9-14, together with the known compounds 7 and 8. A single-crystal X-ray diffraction experiment confirmed the structure of 14. The suppressive effects of compounds 1-14 on the lipopolysaccharide-induced expression of the inducible nitric oxide synthase gene in RAW 264.7 macrophages were examined by a reverse-transcription real-time PCR analysis. With the exception of 7, all other compounds significantly reduced levels of iNOS mRNA relative to control cells, which were induced by LPS alone. Compounds 2, 3, and 5 were similar in activity to dexamethasone, while 9 was more potent.

This study examines the synthesis and antibacterial activities of 5,7-dihydroxycoumarin derivatives, whose structures were confirmed using analytical and spectral data. Twenty compounds were tested for their antibacterial activities against five microbial species such as E. coli, S. aureus, K. pneumonia, P. aeruginosa, and S. typhimurium were studied. Compounds 5 and 12 exhibited the most potent activity against Staphylococcus aureus with a MIC value of 2.5 µg/mL for each of the compounds., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selenium is an essential trace nutrient that has a narrow exposure window between its beneficial and detrimental effects. We investigated how selenium affected the development, fertility, and cholinergic signaling of the nematode, Caenorhabditis elegans. Our results showed that selenite supplementation at 0.01 and 0.05 μM accelerated development and increased the brood size, while the addition of 20 μM selenite retarded the developmental rate and decreased the brood size. We also showed that the 0.01 μM selenite-pretreated nematodes were more resistant to paralysis induced by an acetylcholinesterase inhibitor, aldicarb, and a nicotinic acetylcholine receptor agonist, levamisole, compared to untreated worms. In contrast, 20 μM selenite-pretreated animals were more sensitive to aldicarb- and levamisole-induced paralysis compared to untreated worms. We measured the internal selenium in supplemented worms using inductively coupled plasma atomic emission spectroscopy, and the data obtained suggested that selenite added to growth medium was taken up by the worms. Taken together, these results suggest that selenite exerts both ameliorative and toxic effects on C.elegans, depending on the amount. Our investigations here thus reinforce our understanding of the ameliorative and toxic effects of selenium on development, reproduction, and cholinergic signaling., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen- 2-one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was found to have the most potent activity in protecting porcine γ-crystallin against UVC insults. Results of fluorescence assays indicated that compound 7 was capable of decreasing the loss of intensity while lens crystallins and DNA PUC19 were irradiated with UVC. Presence of compound 7 decreased hydroxyl radical levels determined by probe 1b and the free iron concentrations determined by Ferrozine reagent. The chelation assay showed that compound 7 was chelated to metal via 6-CO and 5-OH on the benzopyrone ring. The observed protective effects of compound 7 towards crystallins from insults of UVC and free radicals may be due to its iron-chelating activity and its peak absorption at 254 nm.