Gehua Jiejiu Dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study.

OBJECTIVE: To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction (, GJDD) on alcoholic fatty live disease (AFLD) by using proteomic methods. METHODS: The male C57BL/6J mouse were randomly divided into four groups: control group, model group, GJDD group and resveratrol group. After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method, the GJDD group and resveratrol group were intragastrically administered with GJDD (4900 mg/kg) and resveratrol (400 mg/kg) respectively, once a day for 9 d. The fat deposition of liver tissue was observed and evaluated by oil red O (ORO) staining. 4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group. The differentially expressed proteins were screened according to protein expression differential multiples, and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Finally, expression validation of the differentially co-expressed proteins from control group, model group and GJDD group were verified by targeted proteomics quantification techniques. RESULTS: In semiquantitative analyses of ORO, all kinds of steatosis (ToS, MaS, and MiS) were evaluated higher in AFLD mice compared to those in GJDD or resveratrol-treated mice. 4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified, of which 3763 proteins were quantified and 946 differentially expressed proteins were screened. Compared with the control group, 145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group. In addition, compared with the model group, 92 proteins were up-regulated and 135 proteins were down-regulated in the liver tissue of the GJDD group. 15 differentially co-expressed proteins were found between every two groups (model group vs control group, GJDD group vs model group and GJDD group vs control group), which were involved in many biological processes. Among them, 11 differentially co-expressed key proteins (Aox3, H1-5, Fabp5, Ces3a, Nudt7, Serpinb1a, Fkbp11, Rpl22l1, Keg1, Acss2 and Slco1a1) were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis. CONCLUSIONS: Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression, likely through the modulation of lipid metabolism, bile acid metabolism and with exertion of antioxidant stress.

Herbs for lochia discharge used among postpartum women in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional Taiwanese culture of "postpartum confinement", the term "lochia discharge" is a synonym for assisting postpartum uterine involution. Postpartum women in Taiwan consult traditional Chinese medicine (TCM) pharmacies to obtain various TCM formulations that facilitate lochia discharge. AIM OF THE STUDY: As an ethnopharmacy study, we aimed to conduct field investigations to explore the herbal composition of TCM formulations for lochia discharge provided by TCM pharmacies in Taiwan and to identify the pharmaceutical implications of these TCM formulations. MATERIALS AND METHODS: Through stratified sampling, we collected 98 formulations for postpartum lochia discharge from TCM pharmacies, which used a total of 60 medicinal materials. RESULTS: The most common plant families of the medicinal materials found in Taiwanese lochia discharge formulations were Fabaceae and Lauraceae. Abiding by the TCM theory of nature and flavor, most drugs were warm in nature and sweet in flavor, and predominantly focused on the traditional functions of qi tonifying and blood activating. Correlation and network analyses of the medicinal components of lochia discharge formulations identified 11 core herbs, which, in the order of most to least frequently used, include Angelica sinensis, Ligusticum striatum, Glycyrrhiza uralensis, Zingiber officinale, Prunus persica, Eucommia ulmoides, Leonurus japonicus, Lycium chinense, Hedysarum polybotrys, Rehmannia glutinosa, and Paeonia lactiflora. These 11 herbs formed a total of 136 drug combinations in the 98 formulations, with 2-7 herbs in each combination. In addition, in the center of the network were A. sinensis and L. striatum, which jointly appeared in 92.8% of the formulations analyzed. CONCLUSIONS: To our knowledge, this is the first study to systematically review lochia discharge formulations in Taiwan. The results of this study could provide an important basis for subsequent research in the clinical efficacy of Taiwanese lochia discharge formulations and the pharmacological mechanisms of their herbal components.

Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia.

BACKGROUND: Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation. RESULTS: Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy. The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via selective disruption of pro-survival mTOR signaling. In vivo biodistribution study demonstrated about 11-fold greater bone marrow accumulation of the nanocomplex compared to free sorafenib. In AML patient-derived xenograft (AML-PDX) mouse model, administration of the nanocomplex effectively eradicated bone marrow-residing leukemic blasts and improved survival rates without noticeable off-target toxicity. CONCLUSION: This study may provide insights into the rational design of nanomedicine platforms enabling bone marrow-targeted delivery of therapeutic agents for the treatment of AML and other bone marrow diseases.

An Ethnopharmaceutical Study on the Hypolipidemic Formulae in Taiwan Issued by Traditional Chinese Medicine Pharmacies.

Globally, approximately one-third of ischemic heart diseases are due to hyperlipidemia, which has been shown to cause various metabolic disorders. This study was aimed to disassemble and analyze hypolipidemic formulae sold by traditional Chinese medicine (TCM) pharmacies. Using commonly used statistical parameters in ethnopharmacology, we identified the core drug combination of the hypolipidemic formulae, thereby exploring the strategy by which the Taiwanese people select hypolipidemic drugs. Most important of all, we preserved the inherited knowledge of TCM. We visited 116 TCM pharmacies in Taiwan and collected 91 TCM formulae. The formulae were mainly disassembled by macroscopical identification, and the medicinal materials with a relative frequency of citation (RFC) >0.2 were defined as commonly used medicinal materials. Subsequently, we sorted the information of medicinal materials recorded in the Pharmacopeia, searched for modern pharmacological research on commonly used medicinal materials using PubMed database, and visualized data based on the statistical results. Finally, the core hypolipidemic medicinal materials used in folk medicine were obtained. Of the 91 TCM formulae collected in this study, 80 traditional Chinese medicinal materials were used, belonging to 43 families, predominantly Lamiaceae. Roots were the most commonly used part as a medicinal material. There were 17 commonly used medicinal materials. Based on medicinal records in Pharmacopeia, most flavors and properties were warm and pungent, the majority traditional effects were "tonifying and replenishing" and "blood-regulating." Besides, the targeted diseases searching from modern pharmacological studies were diabetes mellitus and dyslipidemia. The core medicinal materials consisted of Astragalus mongholicus Bunge and Crataegus pinnatifida Bunge, and the core formulae were Bu-Yang-Huan-Wu-Tang and Xie-Fu-Zhu-Yu-Tang. In addition, 7 groups of folk misused medicinal materials were found. Although these TCMs have been used for a long period of time, their hypolipidemic mechanisms remain unclear, and further studies are needed to validate their safety and efficacy.

Impact of Nutritional Assessment on the Clinical Outcomes of Patients with Non-albicans Candidemia: A Multicenter Study.

Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients' nutritional status before the onset of candidemia. A total of 378 patients were enrolled; 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01; 95% CI, 1.24-3.26; p = 0.005), Charlson comorbidity index (HR, 1.10; 95% CI, 1.03-1.18; p = 0.007), Foley catheter use (HR, 1.68; 95% CI, 1.21-1.35; p = 0.002), concomitant bacterial infections (HR, 1.55; 95% CI, 1.11-2.17; p = 0.010), low platelet count (HR, 3.81; 95% CI, 2.45-5.91; p < 0.001), not receiving antifungals initially (HR, 4.73; 95% CI, 3.07-7.29; p < 0.001), and MUST ≥ 2 (HR, 1.54; 95% CI, 1.09-2.17; p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.

Association of vitamin D levels and risk of latent tuberculosis in the hemodialysis population.

BACKGROUND: Vitamin D is essential in the host defense against tuberculosis (TB). Suboptimal vitamin D status is common in the hemodialysis population. Hemodialysis patients have an increased risk compared to the general population latent tuberculosis infection (LTBI). However, the association between vitamin D deficiency and LTBI in this population remains unclear. MATERIALS AND METHODS: We conducted a cross-sectional study between March and May 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-Tube was used to assess LTBI. Plasma 25-hydroxycholecalciferol (25-OHD) levels were measured by Elecsys Vitamin D Total assay. Suboptimal vitamin D levels included vitamin D insufficiency 20-29 ng/mg and vitamin D deficiency <20 ng/mL. Predictors for LTBI were analyzed. RESULTS: A total of 287 participants were enrolled. The suboptimal vitamin D level was 31.4% (90/287), which including the vitamin D deficiency was 13.9% (40/287). A total of 49.1% (141/287) people received nutritional vitamin D supplementation. The prevalence of IGRA positivity in this study was 25.1% (72/287). There was no significant difference in vitamin D concentrations or the proportion of vitamin D supplementation among the IGRA-positive and IGRA-negative groups (p = 0.789 and 0.496, respectively). In multivariate analysis, age >65 years old (odds ratio (OR), 1.89; 95% CI, 1.08-3.31; p = 0.026) and TB history (OR, 3.51; 95% CI, 1.38-8.91; p = 0.008) were independent predictors of IGRA positivity. CONCLUSION: This is the first study to report that vitamin D deficiency was not associated with IGRA positivity in a hemodialysis population. Aging and TB history were both independent predictors for LTBI.

Taenia saginata Infection Misdiagnosed as Acute Cholecystitis in a Tibetan Patient, in China

The present study reports a rare case of Taenia saginata infection, which was initially diagnosed as acute cholecystitis in a Tibetan patient at the Qinghai-Tibetan Plateau pastoral area, China. A 45-year-old female was initially diagnosed with acute cholecystitis at a hospital in China. She had a slight fever, weight loss and constipation and complained of pain in the upper abdomen and left back areas. Increase of monocyte, eosinophil and basophil levels were shown. Taenia sp. eggs were detected in a fecal examination. An adult tapeworm approximately 146 cm in length, whitish-yellow color, was collected from the patient after treatment with traditional Chinese medicine. The adult tapeworm had a scolex and proglottids with genital pores. The scolex was rectangular shape with 4 suckers and rostellum without hooklet. The cox1 gene sequence shared 99.5-99.8% homology with that of T. saginata from other regions in China. The patient was diagnosed finally infected with T. saginata by morphological and molecular charateristics.

Expression of vesicular glutamate transporter in transient receptor potential vanilloid 1-positive neurons in the rat trigeminal ganglion

Activation of transient receptor potential vanilloid 1 (TRPV1), a calcium permeable channel expressed in primary sensory neurons, induces the release of glutamate from their central and peripheral afferents during normal acute and pathological pain. However, little information is available regarding the glutamate release mechanism associated with TRPV1 activation in primary sensory neurons. To address this issue, we investigated the expression of vesicular glutamate transporter (VGLUT) in TRPV1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) under normal and complete Freund’s adjuvant (CFA)-induced inflammatory pain conditions using behavioral testing as well as double immunofluorescence staining with antisera against TRPV1 and VGLUT1 or VGLUT2. TRPV1 was primarily expressed in small and medium-sized TG neurons. TRPV1+ neurons constituted approximately 27% of all TG neurons. Among all TRPV1+ neurons, the proportion of TRPV1+ neurons coexpressing VGLUT1 (VGLUT1+/ TRPV1+ neurons) and VGLUT2 (VGLUT2+/TRPV1+ neurons) was 0.4% ± 0.2% and 22.4% ± 2.8%, respectively. The proportion of TRPV1+ and VGLUT2+ neurons was higher in the CFA group than in the control group (TRPV1+ neurons: 31.5% ± 2.5% vs. 26.5% ± 1.2%, VGLUT2+ neurons: 31.8% ± 1.1% vs. 24.6% ± 1.5%, p < 0.05), whereas the proportion of VGLUT1+, VGLUT1+/TRPV1+, and VGLUT2+/TRPV1+ neurons did not differ significantly between the CFA and control groups. These findings together suggest that VGLUT2, a major isoform of VGLUTs, is involved in TRPV1 activation-associated glutamate release during normal acute and inflammatory pain.

Taenia saginata Infection Misdiagnosed as Acute Cholecystitis in a Tibetan Patient, in China

The present study reports a rare case of Taenia saginata infection, which was initially diagnosed as acute cholecystitis in a Tibetan patient at the Qinghai-Tibetan Plateau pastoral area, China. A 45-year-old female was initially diagnosed with acute cholecystitis at a hospital in China. She had a slight fever, weight loss and constipation and complained of pain in the upper abdomen and left back areas. Increase of monocyte, eosinophil and basophil levels were shown. Taenia sp. eggs were detected in a fecal examination. An adult tapeworm approximately 146 cm in length, whitish-yellow color, was collected from the patient after treatment with traditional Chinese medicine. The adult tapeworm had a scolex and proglottids with genital pores. The scolex was rectangular shape with 4 suckers and rostellum without hooklet. The cox1 gene sequence shared 99.5-99.8% homology with that of T. saginata from other regions in China. The patient was diagnosed finally infected with T. saginata by morphological and molecular charateristics.

Expression of vesicular glutamate transporter in transient receptor potential vanilloid 1-positive neurons in the rat trigeminal ganglion

Activation of transient receptor potential vanilloid 1 (TRPV1), a calcium permeable channel expressed in primary sensory neurons, induces the release of glutamate from their central and peripheral afferents during normal acute and pathological pain. However, little information is available regarding the glutamate release mechanism associated with TRPV1 activation in primary sensory neurons. To address this issue, we investigated the expression of vesicular glutamate transporter (VGLUT) in TRPV1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) under normal and complete Freund’s adjuvant (CFA)-induced inflammatory pain conditions using behavioral testing as well as double immunofluorescence staining with antisera against TRPV1 and VGLUT1 or VGLUT2. TRPV1 was primarily expressed in small and medium-sized TG neurons. TRPV1+ neurons constituted approximately 27% of all TG neurons. Among all TRPV1+ neurons, the proportion of TRPV1+ neurons coexpressing VGLUT1 (VGLUT1+/ TRPV1+ neurons) and VGLUT2 (VGLUT2+/TRPV1+ neurons) was 0.4% ± 0.2% and 22.4% ± 2.8%, respectively. The proportion of TRPV1+ and VGLUT2+ neurons was higher in the CFA group than in the control group (TRPV1+ neurons: 31.5% ± 2.5% vs. 26.5% ± 1.2%, VGLUT2+ neurons: 31.8% ± 1.1% vs. 24.6% ± 1.5%, p < 0.05), whereas the proportion of VGLUT1+, VGLUT1+/TRPV1+, and VGLUT2+/TRPV1+ neurons did not differ significantly between the CFA and control groups. These findings together suggest that VGLUT2, a major isoform of VGLUTs, is involved in TRPV1 activation-associated glutamate release during normal acute and inflammatory pain.

Progress of researches on the development of non-benzimidazoles for the treatment of echinococcosis / 中国血吸虫病防治杂志

The long-term use of benzimidazoles for the treatment of echinococcosis may cause multiple adverse reactions and low compliance. A search for novel agents, as an alternative of benzimidazoles, is therefore of great significance for the treatment of echinococcosis. This review focuses on the progress of researches on non-benzimidazoles for the clinical treatment of echinococcosis, including anti-parasitic agents, anti-proliferative agents and plant extracts, so as to provide insights into the further development of non-benzimidazoles.

New Model of Traditional Chinese Medicine with Effect of Invigorating Kidney and Filling Sea of Marrow in Regulating Delay in Cortical Maturation of ADHD Based on Theory of Steady Yin and Vexed Yang / 中国实验方剂学杂志

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children. The theory of traditional Chinese medicine (TCM) does not have a special term of this disease, and classifies ADHD to the category of " forgetfulness" " dysphoria" " injudiciousness" according to its clinical manifestations. TCM theoretic and clinical systems for treating ADHD have been developed, but current pharmacodynamics studies of TCM on ADHD have mostly focused on neurotransmitter metabolic system and its receptor signaling pathway to reflect the advantages of multi-component and multi-target effect of TCM, but failed to demonstrate the scientific connotations of TCM theory, such as " coordination between kidney and brain" and " steady Yin and vexed Yang" , and ignored the delay in cortical maturation as the core neuropathology of ADHD. The symptoms relating to " restlessness of Yang" due to Yin deficiency that cannot inhibit hyperactivity of Yang, kidney-Yin deficiency and liver-Yang excess syndrome is the most common syndrome of ADHD, and TCMs with effect of invigorating kidney and filling sea of marrow are mostly used by TCM practitioners. According to anatomy basis of neuronal development disorder, the new theory of " energy metabolism dysfunction" , the pathogenesis hypothesis of sea of marrow development disorder and its relevant clinical practices and experimental studies, substantial basis studies of the therapy for " invigorating kidney and filling sea of marrow" , as well as pharmacodynamics study of <italic>Rehmannia glutinosa</italic> (Shudihuang) for treating ADHD, we put forward ADHD pathogenesis that " restlessness of Yang due to Yin deficiency" is related to the disorder of executive function due to the delay in cortical maturation, energy metabolism dysfunction and neurodevelopmental disorder, and regarded that TCMs with effect of invigorating kidney and filling sea of marrow are the most commonly used to treat ADHD, and improve delay in cortical maturation corresponding to sea of marrow insufficiency by regulating dysfunction of neurodevelopment and energy metabolism, so as to relieve the core symptoms of ADHD. The new treatment model of TCM with effect of invigorating kidney and filling sea of marrow for treating ADHD will provide a theoretical basis for improving the clinical efficacy of ADHD.

Carrier-Enhanced Anticancer Efficacy of Sunitinib-Loaded Green Tea-Based Micellar Nanocomplex beyond Tumor-Targeted Delivery.

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3-O-gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG-b-poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumor-targeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier-drug synergies with the high-performance carrier of PEG-EGCG besides tumor-targeted delivery.

Clinical characteristics of Candida tropicalis fungaemia with reduced triazole susceptibility in Taiwan: a multicentre study.

Candida tropicalis is the second most common Candida species causing fungaemia in Taiwan, and decreased susceptibility to fluconazole has been reported. This study analysed the clinical characteristics of adult patients with C. tropicalis fungaemia and the antifungal susceptibilities of isolates at five tertiary hospitals in Taiwan (1 July 2011 to 30 June 2014). A standardised case record form was used retrospectively to collect demographic, clinical and microbiological characteristics, antifungal treatment and outcomes. MICs of non-duplicate isolates were determined using SensititreTM YeastOneTM and were interpreted using cut-off values recommended by the CLSI. A total 248 patients were diagnosed over the study period; 30-day crude mortality was 52.0%. Multivariate analysis showed that high Charlson comorbidity index ≥4 (OR = 2.09, 95% CI 1.22-3.59; P = 0.008), neutropenia (OR = 4.61, 95% CI 1.42-15.00; P = 0.011) and treatment with an azole-based regimen (OR = 0.39, 95% CI 0.17-0.90; P = 0.028) were significantly associated with 30-day mortality. A total of 33.9% of isolates were non-susceptible to fluconazole (MIC50, 2 mg/L; MIC90, 16 mg/L; MIC range, 0.25 to >256 mg/L), whilst 56.9% to voriconazole (MIC50, 0.25 mg/L; MIC90, 1 mg/L; MIC range, 0.015 to >8 mg/L) according to CLSI clinical breakpoints. There was no significant correlation between overall mortality and MICs of fluconazole or voriconazole. This study showed high mortality in patients with C. tropicalis fungaemia, and azole-based antifungal treatment could improve outcomes regardless of fluconazole MICs of infecting isolates compared with patients without any treatment within 48 h.

Two symmetrical unsaturated acids isolated from Viscum album / 中国天然药物

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.

Combined Extracts of Artemisia and Green Tea, Mitigated Alcoholic Gastritis Via Enhanced Heat-shock Protein 27 / 대한소화기학회지

BACKGROUND/AIMS: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. METHODS: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. RESULTS: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. CONCLUSIONS: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.

Randomized, Double-blind, Placebo-controlled Clinical Trial for the Evaluation of the Efficacy and Safety of Artemisia and Green Tea Extract SD1003F in Volunteers with Helicobacter pylori-associated Gastric Discomfort

BACKGROUND/AIMS: A previous study showed that dietary intervention with Artemisia and green tea extracts, i.e., SD1003F, relieved Helicobacter pylori-associated chronic atrophic gastritis in a mouse model. We continue the research through the current randomized double-blind clinical trial to evaluate the efficacy and safety of the intervention for H. pylori-associated gastric discomfort. MATERIALS AND METHODS: Forty-nine volunteers who tested positive for H. pylori infection received either placebo or SD1003F for 10 weeks and their functional dyspepsia-related quality of life (QOL) was evaluated. H. pylori infection using a urea breath test (UBT), measurement of pepsinogen level using GastroPanel. Adverse effects with biochemical changes were also evaluated. RESULTS: SD1003F administration significantly improved health related-QOL, including dietary intake, emotional stability, life pattern, and social factors relevant to gastric discomfort, in comparison to the control (P < 0.05). The mean UBT measurement significantly decreased in the SD1003F group (P < 0.05). In 2 of the 24 volunteers, SD1003F alone eradicated H. pylori infection, with significant improvements in endoscopic findings. GastroPanel analysis revealed significant improvements that reflect rejuvenation of gastric atrophy in the SD1003F group. No significant side effect was observed in any participant. CONCLUSIONS: SD1003F (Artemisia and green tea extract), is a potential phytochemical to improve H. pylori-associated gastric discomfort.

Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient-Derived Xenografts.

There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P < 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035-44. ©2017 AACR.

Risk Factors for Vitamin D, Zinc, and Selenium Deficiencies in Korean Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. METHODS: We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. RESULTS: Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn’s disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency. CONCLUSIONS: Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients.

Heme Oxygenase-1 Induction and Anti-inflammatory Actions of Atractylodes macrocephala and Taraxacum herba Extracts Prevented Colitis and Was More Effective than Sulfasalazine in Preventing Relapse

BACKGROUND/AIMS: In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. METHODS: Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration. RESULTS: In vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction. CONCLUSIONS: Because the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.