Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Comprehensive analysis of the expression and prognosis for S100 in human ovarian cancer: A STROBE study.

S100 family members are frequently deregulated in human malignancies, including ovarian cancer. However, the prognostic roles of each individual S100 family member in ovarian cancer (OC) patients remain elusive. In the present study, we assessed the prognostic roles and molecular function of 20 individual members of the S100 family in OC patients using GEPIA, Kaplan-Meier plotter, SurvExpress, GeneMANIA and Funrich database. Our results indicated that the mRNA expression levels of S100A1, S100A2, S100A4, S100A5, S100A11, S100A14, and S100A16 were significantly upregulated in patients with OC, and high mRNA expression of S100A1, S100A3, S100A5, S100A6, and S100A13 were significantly correlated with better overall survival, while increased S100A2, S100A7A, S100A10, and S100A11 mRNA expressions were associated with worse prognosis in OC patients. In stratified analysis, the trends of high expression of individual S100 members were nearly the same in different pathological grade, clinical stage, TP53 mutation status, and treatment. More importantly, S100 family signatures may be useful potential prognostic markers for OC. These findings suggest that S100 family plays a vital role in prognostic value and could potentially be an S100-targeted inhibitors for OC patients.

Structural characterization and anti-alcoholic liver injury activity of a polysaccharide from Coriolus versicolor mycelia.

Polysaccharopeptide (PSP) from the medicinal mushroom Coriolus versicolor has been widely used in Asia as an adjunctive immunotherapy for treating cancers and liver diseases. However, the composition and structure of bioactive components in PSP remain elusive. Herein, we purified a hepatoprotective polysaccharide (PSP-1b1) with a molecular weight of 21.7 kDa from C. versicolor mycelia in submerged culture. PSP-1b1 consists of fucose, galactose, xylose, mannose, glucuronic acid and glucose at a relative molar ratio of 0.16:0.60:0.02:0.55:0.04:1.00. Structural features were investigated by methylation and gas chromatography-mass spectrometry, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The PSP-1b1 backbone consists of →4)-α-Galp-(1 → 4)-α-Galp-(1 → 2)-α-Manp-(1 → 4)-α-Galp-(1 → 2)-α-Manp-(1 → 4)-α-Galp-(1 → 4)-α-Galp-(1 → 2)-α-Manp-(1 → 4)-α-Galp-(1 → 2)-α-Manp-(1 → 4)→, with branches of α-1,6-Manp, ß-1,6-Glcp, ß-1,3,6-Glcp, α-1,3-Manp, α-1,6-Galp, α-1,3-Fucp, T-α-Glcp and T-α-Galp on the O-6 position of α-Manp of the main chain, and secondary branches linked to the O-6 position of ß-Glcp of the major branch. Treatment with PSK-1b1 (80 and 160 mg/kg/day) resulted in hepatoprotective effects against alcohol-induced liver injury in mice by reducing oxidative stress and modulating immunity.

Promotion of Metabolite Synthesis in Isaria cicadae, a Dominant Species in the Cicada Flower Microbiota, by Cicada Pupae.

Cicada flowers, which are edible and medicinal mushrooms, are the fruiting bodies of Isaria cicadae, a fungus that is parasitic on the larvae of cicada pupae. We hypothesize that host factors might possess stimulatory activity on metabolite synthesis in Isaria cicadae. Here, we first compared the microbial community structures of different wild cicada flowers across geographical regions, compartments, and growth stages via high-throughput sequencing. Isaria cicadae TZC-3, an isolate of the most abundant operational taxonomic unit (OTU6782) in all the fungal communities, was isolated from wild cicada flowers. Furthermore, the effects of cicada pupae on metabolite synthesis in Isaria cicadae TZC-3 were studied in submerged culture. The contents of intercellular polysaccharides, adenosine, N6-(2-hydroxyethyl)-adenosine, free amino acids, and hydrolyzed monosaccharides in the mycelia cultured with cicada pupa powder (4%) were significantly increased as compared with the contents in the control group. This indicates that a cicada pupa can act as an elicitor for metabolite synthesis in Isaria cicadae.

Effects of dexamethasone on post-operative cognitive dysfunction and delirium in adults following general anaesthesia: a meta-analysis of randomised controlled trials.

BACKGROUND: Several studies have investigated the effects of dexamethasone on post-operative cognitive dysfunction (POCD) or post-operative delirium (POD); however, their conclusions have been inconsistent. Thus, we conducted a meta-analysis to determine the effects of dexamethasone on POCD and POD in adults following general anaesthesia. METHODS: The Cochrane Central Register of Controlled Trials (2018, Issue 11 of 12) in the Cochrane Library (searched 17 November 2018), MEDLINE OvidSP (1946 to 16 November 2018) and Embase OvidSP (1974 to 16 November 2018) were searched for randomised controlled trials that evaluated the incidence of POCD and POD following dexamethasone administration in adults (age ≥ 18 years) under general anaesthesia. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess the quality of the evidence. RESULTS: Five studies were included (three studies with 855 participants in the dexamethasone group and 538 participants in the placebo group for the incidence of POCD, and two studies with 410 participants in the dexamethasone group and 420 participants in the placebo group for the incidence of POD). There was no significant difference between the dexamethasone group and the placebo group in terms of the incidence of POCD 30 days after surgery (RR [relative risk] 1.00; 95% CI [confidence interval: 0.51, 1.96], P = 1.00, I2 = 77%) or the incidence of POD (RR 0.96; 95% CI [0.68, 1.35], P = 0.80, I2 = 0%). However, both analyses had some limitations because of limited evidence and clinical heterogeneity, and we considered the quality of the evidence for the post-operative incidence of POCD and POD to be very low. CONCLUSIONS: This meta-analysis revealed that prophylactic dexamethasone did not reduce the incidence of POCD and POD. Trials of alternative preventive strategies for POCD and POD, as well as a better understanding of the pathophysiology of those complex syndromes, are still needed to make progress in this field. TRIAL REGISTRATIONR: This study is registered with PROSPERO, 23 October 2018, number CRD42018114552. Available from  https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H⁺ Transporting V1 Subunit C1.

Activated hepatic stellate cells (aHSCs) play a key role in liver fibrosis. During the regression of fibrosis, aHSCs are transformed into inactivated cells (iHSCs), which are quiescent lipid-containing cells and express higher levels of lipid-related genes, such as peroxisome proliferators-activated receptors gamma (PPARγ). Here, we investigated the role of MicroRNA29a (Mir29a) in the resolution of liver fibrosis. Mir29a and lipid-related genes were up-regulated after the recovery of CCl4-induced liver fibrosis in mice. PPARγ agonist rosiglitazone (RSG) promoted de-differentiation of aHSCs to iHSCs and up-regulated MIR29a expression in a human HSC cell line LX-2. MIR29a mimics in vitro promoted the expression of lipid-related genes, while decreased the expression of fibrosis-related genes. MIR29a inhibitor showed the reverse effects. ATPase H⁺ transporting V1 subunit C1 (Atp6v1c1) was increased in liver fibrosis, while down-regulated after the recovery in mice, and negatively regulated by MIR29a in LX-2 cells. Knockdown of ATP6V1C1 by siRNA decreased alpha-smooth muscle actin (α-SMA) and increased lipid-related genes expression. Simultaneous addition of MIR29a mimics and ATP6V1C1 siRNA further increased RSG promoted expression of lipid-related proteins in vitro. Collectively, MIR29a plays an important role during the trans-differentiation of aHSCs in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1.

Fluvastatin-mediated down-regulation of SATB1 affects aggressive phenotypes of human non-small-cell lung cancer cell line H292.

AIMS: Fluvastatin reduces tumor proliferation and increased apoptotic activity in various cancers. Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that reprogrammes the gene transcription profiles of tumors to promote growth and metastasis. The antitumor effect and molecular mechanisms of fluvastatin on lung cancer is poorly understood. This study aimed to investigate the antitumor effect of fluvastatin on lung cancer and its possible mechanics. MAIN METHODS: Cell viability assay was used to examine the inhibition of fluvastatin on proliferation of H292 cells. In order to investigate the antitumor mechanics, SATB1 knock-down H292 cells was constructed by lentiviral transfection. RT-PCR and Western blot were performed to examine the effects of fluvastatin on expression of SATB1 and Wnt/ß-catenin signaling components. KEY FINDINGS: Fluvastatin significantly inhibited proliferation and invasion of H292 cells in a time- and dose-dependent manner and promoted the apoptosis (p < 0.05). The expression of SATB1 was down-regulated by fluvastatin in a dose-dependent manner. The proliferation and invasion of SATB1-shRNA cells was significantly suppressed, and the apoptosis was significantly enhanced (p < 0.05). We also show that the common target genes were regulated by SATB1 and Wnt/ß-catenin pathway simultaneously. There may be a functional link between SATB1 and Wnt/ß-catenin pathway. SIGNIFICANCE: We presented a possible mechanism of statins that fluvastatin significantly suppressed the in vitro tumor progression of H292 cells possibly by down-regulation of SATB1 via Wnt/ß-catenin pathway, which provided new therapeutic possibilities for more cancers driven by hyperexpression of SATB1 and Wnt/ß-catenin pathway.

Effects of different doses of intranasal dexmedetomidine on preoperative sedation and postoperative agitation in pediatric with total intravenous anesthesia undergoing adenoidectomy with or without tonsillectomy.

Dexmedetomidine is a highly selective α2 receptor agonist, this study aimed to investigate the effects of different doses of intranasal dexmedetomidine on the preoperative sedation and postoperative agitation in pediatric with total intravenous anesthesia (TIVA) for adenoidectomy with or without tonsillectomy.This is a double-blind placebo-controlled randomized trial. Pediatric were randomly divided into the D1, D2, and S groups, each group contained 30 patients. Twenty-five to 40 minutes before surgery, the D1 and D2 groups received intranasally dexmedetomidine 1 µg kg or 2 µg kg, respectively, while the S group received saline of the same volume. A unified protocol of TIVA induction and maintenance was used for the three groups. The preoperative sedation, behavior of separation from parents, postoperative agitation, and postoperative pain of the children were evaluated.The proportions of satisfactory sedation in the D1, D2, and S groups were 63.3%, 76.7%, and 0%, respectively. There was a statistically significant difference between D1 and S groups (P = .000) and D2 versus S groups (P = .000), while there was no statistically significant difference between D1 and D2 groups (P = .399). As for scale on the behavior of separation from parents, there was a statistically significant difference between D1 and S groups (P = .009) and D2 versus S groups (P = .009), whereas there was no significant difference between D1 and D2 groups (P = 1). The incidence of postoperative agitation in the D1, D2, and S groups was 43.3%, 30.0%, and 63.3%, respectively, and there was a statistical difference between D2 and S groups (P = .010). There was a significant difference in the Pediatric Anesthesia Emergence Delirium (PAED) scale between D2 and S groups (P = .029). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) in the D2 group was significantly lower than the S group (P = .013).The intranasal dexmedetomidine of 1 or 2 µg kg 25 to 40 minute before induction of anesthesia both could deliver effective preoperative sedation, reducing the children's distress of separation from parents. Moreover, intranasal dexmedetomidine of 2 µg kg could deliver more effective postoperative analgesia and reduce postoperative agitation, without prolonging postoperative recovery or causing severe adverse events.

Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress, inflammation-related signaling pathways and modulating the composition of the gut microbiota.

Inflammatory bowel disease (IBD) is a disease caused by a dysregulated immune with unknown etiology. Hericium erinaceus (H. erinaceus) is a Chinese medicinal fungus, with the effect of prevention and treatment of gastrointestinal disorders. In this study, we have tested the anti-inflammatory effect of polysaccharide of H. erinaceus (HECP, Mw: 86.67 kDa) in the model of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. Our data indicated that HECP could improve clinical symptoms and down-regulate key markers of oxidative stresses, including nitric oxide (NO), malondialdehyde (MDA), total superoxide dismutase (T-SOD), and myeloperoxidase (MPO). HECP also suppressed the secretion of interleukin (IL)-6, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and decreased the expression of related mRNA. Meanwhile, HECP blocked phosphorylation of nuclear factor-κB (NF-κB) p65, NF-κB inhibitor alpha (IκB-α), mitogen-activated protein kinases (MAPK) and Protein kinase B (Akt) in DSS-treated mice. Moreover, HECP reversed DSS-induced gut dysbiosis and maintained intestinal barrier integrity. In conclusion, HECP ameliorates DSS-induced intestinal injury in mice, which suggests that HECP can serve as a protective dietary nutrient against IBD.

Bioassay-guided fractionation of ethyl acetate extract from Armillaria mellea attenuates inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 microglia.

BACKGROUND: Armillaria mellea (A. mellea) is a traditional Chinese medicinal and edible mushroom, which is proved to possess a lot of biological activities, including anti-oxidation, immunopotentiation, anti-vertigo and anti-aging activities. However, little information is available in regard to its neuroprotection activity in inflammation-mediated neurodegenerative diseases. PURPOSE: We have found that A. mellea has an anti-inflammatory activity in LPS-induced RAW264.7 cells in our previous study. The objective of this study is to investigate the anti-neuroinflammatory mechanism of a bioassay-guided fractionation (Fr.2) and its active components/compounds. METHODS: Compounds were isolated by preparative high performance liquid chromatography (pre-HPLC) and their structures were established by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic analyses. The anti-neuroinflammatory effect of Fr.2 and each compounds were investigated in lipopolysaccharide (LPS)-stimulated murine microglia cell lineBV-2. RESULTS: We demonstrated that Fr.2 significantly decreased the production of inflammation mediator nitric oxide (NO) and inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1ß) in a dose-dependent manner (10, 30, 100µg/ml). In addition, Fr.2 markedly down-regulated the phosphorylation levels of nuclear factor kappa B p65 (NF-κB p65), inhibitory κB-α (IκB-α) and c-Jun N-terminal kinases (JNKs) pathways. Sevens compounds were isolated from Fr.2, among them, three compounds, 5-hydroxymethylfurfural (CP1), vanillic acid (CP4) and syringate (CP5) were reported for the first time in A. mellea. NO and inflammatory cytokines (TNF-α, IL-6, IL-1ß) secretion indicated that daidzein (CP6) and genistein (CP7) showed a more outstanding anti-inflammation potential at non-toxic concentrations (10, 30, 100µM) than the other five compounds. CONCLUSIONS: In conclusion, Fr.2 may have therapeutic potential for neurodegenerative diseases by inhibiting inflammatory mediators and suppress inflammation pathway in activated microglia. Daidzein and genistein may serve as the effective anti-inflammation compounds of Fr.2.

The common dietary flavonoid myricetin attenuates liver fibrosis in carbon tetrachloride treated mice.

SCOPE: Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated. METHODS AND RESULTS: Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor ß1 (TGF-ß1) or platelet-derived growth factor BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-ß1- or PDGF-BB-induced HSCs activation, cell migration, and extracellular matrix production; blocked TGF-ß1-induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK), and protein kinase B (Akt); and downregulated PDGF-BB stimulated phosphorylation of extracellular signal-regulated kinase and Akt in HSCs in a dose-dependent manner. Meanwhile, the carbon tetrachloride (CCl4 ) induced mouse model has been used to study antifibrosis role of myricetin in vivo. Our data demonstrated that myricetin suppressed α-smooth muscle actin and collagen type I deposition and blocked phosphorylation of Smad2, mitogen-activated protein kinases, and Akt in CCl4 -treated mice. CONCLUSION: Myricetin inhibits the activation of HSCs and ameliorates CCl4 -induced liver fibrosis in mice and may serve as a potential therapeutic agent in the treatment of liver fibrosis.

IL-6/STAT3/SOCS3 signaling pathway playing a regulatory role in ulcerative colitis carcinogenesis.

OBJECTIVE: Large-scale clinical studies have shown that ulcerative colities were related with colorectal cancer. In this study, animal model was established by AOM/DSS method to explore the activation of IL-6-STAT3-SOCS3 signaling pathway and the expression of pathway-related proteins in ulcerative colitis carcinogenesis, in order to lay a foundation for exploring the regulation mechanism of IL-6/STAT3/SOCS3 signaling pathway in ulcerative colitis carcinogenesis. METHOD: AOM/DSS modeling method was used to establish animal models of ulcerative colitis carcinogenesis; colonic mucosa specimens were collected at different time points for pathological examination. Immunohistochemical method and western blot were used to detect the expression of IL6, STAT3 and SOCS3 protein in the control group, UC model + empty vector group and UC model + STAT3 knockout group. RESULTS: In UC model + empty vector group, IL6 and STAT3 expression was increased as lesion degree increased (P < 0.05). The expression of SOCS3 was weakened and the degree of activation decreased (P < 0.05). IL6 expression increased in UC model + STAT3 knockout group (P < 0.05) while the expression of SOCS3 decreased; compared with the UC model + empty vector group, there was a significant difference (P < 0.05). CONCLUSION: The expression and activation of IL6 and STAT3 expression were enhanced in ulcerative colitis carcinogenesis, and their expression increased with the lesion degree increased, reflecting the disease progression to a certain extent. The expression and activation of SOCS3 expression decreased. STAT3 had a certain effect on the expression of SOCS3, playing a certain regulatory role in ulcerative colitis carcinogenesis.

Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells.

AIM: To investigate the changes in apoptosis in gastrointestinal cancer cells from patients with gastrointestinal cancers treated with arsenic trioxide (As2O3); and to study the possible molecular mechanisms of such changes by detecting the expression levels of p53 and Bcl-2. METHODS: Twenty patients with gastrointestinal adenocarcinoma based on endoscopic and biopsy findings (ten patients with gastric cancer and ten patients with colorectal cancer) who received treatment in our hospital between August 2007 and December 2008 were included in this study. None of the patients had received anti-tumour agents prior to As2O3 treatment. As2O3 was administered intravenously at a dose of 0.01 g/d diluted with 5% glucose in normal saline for 2-3 h for 3 consecutive days before surgery. Morphological changes associated with apoptosis of gastrointestinal cancer cells were observed by light microscopy. Changes in the apoptotic index induced by As2O3 were investigated using the terminal deoxynucleotidyl transferase dUTP nick end labelling method. Expression levels of p53 and Bcl-2 proteins in gastrointestinal cancer tissues were determined by immunohistochemistry. RESULTS: The apoptotic index of human gastrointestinal cancer cells was higher in cells from patients treated with As2O3 than in those not treated (P < 0.05). p53 protein expression in gastrointestinal tissues was unchanged by As2O3 (P > 0.05). However, Bcl-2 protein expression in gastrointestinal tissues was down-regulated by As2O3 (P < 0.01). CONCLUSION: These results demonstrate that As2O3 treatment in patients with gastrointestinal cancers can induce apoptosis in gastrointestinal cancer cells and down-regulate Bcl-2 protein expression.

Safety and efficacy of radiation and chemoradiation in patients over 70 years old with inoperable esophageal squamous cell carcinoma.

The aim of the present study was to perform a retrospective analysis to investigate the outcome and toxicity of radiation (RT) and chemoradiation (CRT) in elderly, inoperable patients >70 years old. Between 2003 and 2012, 1,024 patients with squamous cell carcinoma (SCC) of the esophagus were treated at the Department of Thoracic Cancer, West China Hospital (Chengdu, China). Of these patients, 37 were >70 years old and had not undergone surgery, and were selected for analysis. Of these 37 patients, CRT had been administered to 20 (54%). Actuarial survival rates were determined by the Kaplan-Meier method. The one-year survival rate in the CRT group (n=20) was 85%, while 35% of patients in the RT group (n=17) survived for more than one year. The overall and progression-free survival in the CRT group versus the RT group were 17 months [95% confidence interval (CI), 11.861-22.139] versus eight months (95% CI, 6.674-9.326) (P=0.013) and 14 months (95% CI, 9.617-18.383) versus five months (95% CI, 2.311-7.689) (P=0.01), respectively. Patients irradiated with a dose of >50 Gy exhibited an improved survival rate compared with patients who received a dose of ≤50 Gy (18 vs. 14 months; P=0.049). Furthermore, patients with an Eastern Cooperative Oncology Group (ECOG) score of ≤1 had an improved prognosis compared with those with an ECOG score of 2 (14 vs. seven months; P=0.006). The two regimens were well-tolerated and there were no therapy-associated mortalities. The current retrospective study indicated that patients of >70 years old with inoperable esophageal SCC and a good ECOG score exhibit comparably better safety levels with CRT and improved survival rates compared with RT alone.

[Effect of promoter polymorphism of organic cation transporter OCTN1/2 on the susceptibility to Crohns disease: a Meta-analysis].

OBJECTIVE: To investigate the associations between polymorphisms of organic cation transporter OCTN1/2 (organic cation transporter 1/2) and the susceptibility of Crohn's disease (CD) through a meta-analysis. METHODS: Databases of PubMed, EMBASE, MedLine, and CNKI (Chinese), Wanfang (Chinese) were searched for published case control studies on the association between polymorphisms of OCTN1/2 gene and the susceptibility of CD which were published before September 2012. The meta-analysis was applied with Review Manager 4.2 software and Stata 10.0 software. RESULTS: Nineteen eligible studies, including 14 from Europeans, 3 from Asians, 1 from Oceania, and 1 from the US were included in the meta-analysis. In total, significant associations were found between OCTN1/2 polymorphisms and the susceptibility of CD for all genetic models. In subgroup analyses, significant associations were found in the European population for OCTN1/2. Associations were not significant in the non-European population for OCTN1 (TT vs. CT: OR = 1.25, 95%CI: 0.75 - 1.98, P = 0.34; TT vs. CC + CT: OR = 1.48, 95%CI: 0.95 - 2.29, P = 0.08) and for OCTN2 (CC vs. GC: OR = 1.03, 95%CI: 0.68 - 1.56, P = 0.89; CC vs. GG + GC: OR = 1.23, 95%CI: 0.83 - 1.82, P = 0.31). However, there were significant associations found between OCTN1/2 (TT vs. CC, TT + CT vs. CC, CC vs. GG, CC + GC vs. GG) polymorphisms and the susceptibility of CD found in the non-European population. CONCLUSION: Results from this meta-analysis suggested that OCTN1/2 polymorphisms were associated with the susceptibility of CD in the European population. Associations between OCTN1/2 polymorphisms and the susceptibility of CD in the non-European population required searching for large samples to confirm the findings.

Bioassay-guided isolation of DPP-4 inhibitory fractions from extracts of submerged cultured of Inonotus obliquus.

Inonotus obliquus is a medicinal mushroom used in Russian and Eastern European folk medicine for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes. Previous studies in our laboratory have demonstrated that the mycelium powders of I. obliquus possess significant antihyperglycemic effects in a mouse model of diabetic disease induced by alloxan. However, the active ingredients of mycelium powders responsible for the diabetes activity have not been identified. This study aims to identify the active ingredients of I. obliquus mycelium powders by a bioassay-guided fractionation approach and explore the mechanism of action of these active ingredients by using a well-established DPP-4 (an important enzyme as a new therapeutic target for diabetes) inhibitory assay model. The results showed the chloroform extract of mycelium was potential inhibitory against DPP-4. Bioactivity guided fractionation led to the identification of 19 compounds using UPLC-Q-TOF-MS. Molecular docking between the compounds and DPP-4 revealed that compounds 5, 8, 9, 14, 15 may be the active components responsible for the DPP-4 inhibitory activity.

Further studies on the hepatoprotective effect of Antrodia camphorata in submerged culture on ethanol-induced acute liver injury in rats.

To further understand the hepatoprotective activity of Antrodia camphorata in living systems and the possible mechanisms of this protection, the effects of fractions from A. camphorata in submerged culture on the liver and its antioxidative system in acute ethanol intoxicated rats were investigated. The results showed that the ethanolic extract (Fr-I) of A. camphorata was the most effective in the prevention of ethanol-induced acute liver injury and free radical generation in rats. The ethanolic extract administrated prior to ethanol significantly prevented the increase in serum levels of hepatic enzyme markers such as aspartate aminotransferase and alanine aminotransferase. It also normalised the increase of hepatic malondialdehyde concentration and the decrease of glutathione levels in the liver. Moreover, Fr-I improved the ethanol-induced decrease of hepatic glutathione peroxidase and reductase activities. On the basis of these results, the ethanolic extract of A. camphorata may exert its hepatoprotective activity by up-regulating GSH-dependent enzymes and inhibiting free radical formation in the liver.

Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases.

Niuchangchih (Antrodia camphorata (M. Zang & C.H. Su) Sheng H. Wu, Ryvarden & T.T. Chang) is a basidiomycete endemic to Taiwan. It is well known as a Traditional Chinese Medicine (TCM), and Taiwanese aborigines used this species to treat liver diseases and food and drug intoxication. The compounds identified in Niuchangchih are predominantly polysaccharides, triterpenoids, steroids, benzenoids and maleic/succinic acid derivatives. Recent research has revealed that Niuchangchih possesses extensive biological activity, such as hepatoprotective, antihypertensive, anti-hyperlipidemic, immuno-modulatory, anticancer, anti-inflammatory and antioxidant activities. The fruiting bodies and fermented products of Niuchangchih have been reported to exhibit activity when treating liver diseases, such as preventing ethanol-, CCl(4)- and cytokine-induced liver injury, inhibiting the hepatitis B virus, ameliorating fatty liver and liver fibrosis, and inhibiting liver cancer cells. This review will address the protective effects of Niuchangchih on the pathological development of liver diseases, and the underlying mechanisms of action are also discussed.

[Clinical observation on percutaneous autologous bone marrow grafting for treatment of fracture nonunion].

OBJECTIVE: To observe the effectiveness of percutaneous bone marrow grafting for treatment of fractures nonunion. METHODS: From June 2001 to December 2007, 29 consecutive cases of fractures nonunion were treated with percutaneous autologous bone marrow grafting included 20 males and 9 females, ranging in age from 20 to 71 years, with an average of 40 years. All the cases were traumatic fractures involving 13 of tibia, 10 of femur, 3 of humerus, 2 of ulna, 1 of radius, 11 cases of them were open fractures. All the cases were performed internal or external fixation before marrow grafting, intramedullary pin in 15 cases, plate in 12 cases, external fixator in 2 cases. The time from injury to therapy were from 6 to 12 months, with an average of 8.5 months. The type of nonunion included atrophic in 26 cases,hypertrophic in 3 cases. All the cases were performed 3 times injection, the interval was 1 month. According to the different fracture, the amount of bone marrow was from 6 to 15 ml. RESULTS: All the 29 cases were followed-up for from 5 to 22 months with an average of 14 months. Four of them were not observed obvious callus after 3 months from the 3rd injection, judged unsuccessful therapy, changed to perform autologous bone grafting (3 of them re-internal fixation), the follow-up ended. The other 25 cases obtained bone union during 3 to 8 months with an average of 4.5 months, the follow-up ended at the time of internal fixation removal. CONCLUSION: Percutaneous autologous bone marrow grafting is an effective, easy and economic therapy for fracture nonunion. But stable internal or external fixation is the premise. Excessive bone defect, the gap more than 5 mm and mal-align requiring rectification is not appropriate for this therapy.