[Iridoids of wine-processed Corni Fructus].

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7ß-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7ß-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7ß-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).

Maternal multivitamin supplementation is associated with a reduced risk of autism spectrum disorder in children: a systematic review and meta-analysis.

Several studies have explored the link of antenatal multivitamin supplementation with autism spectrum disorder (ASD) in offspring, but the findings are inconsistent. The purpose of the current study was to perform a systematic review and meta-analysis of published studies to evaluate the actual association between maternal multivitamin supplementation during the prenatal period and the risk of ASD in children. PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Library were searched up to August 26, 2018. The random-effects model was used to calculate the pooled results. The adjusted risk ratios (RRs) were used as the common measure of association among studies. Sensitivity and subgroup analyses were also conducted. A total of 5 articles (9 independent trials; 231 163 children encompassing 4459 cases) were included. The results of overall analysis showed that the likelihood of ASD in offspring whose mothers used multivitamin supplements during the prenatal period was significantly reduced compared with that in offspring of mothers without such supplementation (RR, 0.62; 95% CI, 0.45-0.86; P = .003). Additionally, the primary outcome of the meta-analysis was quite robust after being verified by sensitivity analyses and no publication bias was found. Furthermore, the findings of overall analysis were generally consistent with those of subgroup analyses. In conclusion, this meta-analysis supports a protective association between maternal multivitamin supplementation during the prenatal period and the subsequent risk of ASD in children. Further investigation is needed and should address the constituent(s) contributing to the protective effect of multivitamin on ASD risk and the underlying molecular mechanisms.

MARESIN 1 PREVENTS LIPOPOLYSACCHARIDE-INDUCED NEUTROPHIL SURVIVAL AND ACCELERATES RESOLUTION OF ACUTE LUNG INJURY.

Acute lung injury (ALI) is characterized by lung inflammation and diffuse infiltration of neutrophils. Neutrophil apoptosis is recognized as an important control point in the resolution of inflammation. Maresin 1 (MaR1) is a new docosahexaenoic acid-derived proresolving agent that promotes the resolution of inflammation. However, its function in neutrophil apoptosis is unknown. In this study, isolated human neutrophils were incubated with MaR1, the pan-caspase inhibitor z-VAD-fmk, and lipopolysaccharide (LPS) to determine the mechanism of neutrophil apoptosis. Acute lung injury was induced by intratracheal instillation of LPS. In addition, mice were treated with MaR1 intravenously at the peak of inflammation and administered z-VAD-fmk intraperitoneally. We found that culture of isolated human neutrophils with LPS dramatically delayed neutrophil apoptosis through the phosphorylation of AKT, ERK, and p38 to upregulate the expression of the antiapoptotic proteins Mcl-1 and Bcl-2, which was blocked by pretreatment with MaR1 in vitro. In mice, MaR1 accelerated the resolution of inflammation in LPS-induced ALI through attenuation of neutrophil accumulation, pathohistological changes, and pulmonary edema. Maresin 1 promoted resolution of inflammation by accelerating caspase-dependent neutrophil apoptosis. Moreover, MaR1 also reduced the LPS-induced production of proinflammatory cytokines and upregulated the production of the anti-inflammatory cytokine interleukin-10. In contrast, treatment with z-VAD-fmk inhibited the proapoptotic action of MaR1 and attenuated the protective effects of MaR1 in LPS-induced ALI. Taken together, MaR1 promotes the resolution of LPS-induced ALI by overcoming LPS-mediated suppression of neutrophil apoptosis.

Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial.

OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.

Maresin 1 mitigates LPS-induced acute lung injury in mice.

BACKGROUND AND PURPOSE: Acute lung injury (ALI) is a severe illness with a high rate of mortality. Maresin 1 (MaR1) was recently reported to regulate inflammatory responses. We used a LPS-induced ALI model to determine whether MaR1 can mitigate lung injury. EXPERIMENTAL APPROACH: Male BALB/c mice were injected, intratracheally, with either LPS (3 mg·kg(-1) ) or normal saline (1.5 mL·kg(-1) ). After this, normal saline, a low dose of MaR1 (0.1 ng per mouse) or a high dose of MaR1 (1 ng per mouse) was given i.v. Lung injury was evaluated by detecting arterial blood gas, pathohistological examination, pulmonary oedema, inflammatory cell infiltration, inflammatory cytokines in the bronchoalveolar lavage fluid and neutrophil-platelet interactions. KEY RESULTS: The high dose of MaR1 significantly inhibited LPS-induced ALI by restoring oxygenation, attenuating pulmonary oedema and mitigating pathohistological changes. A combination of elisa and immunohistochemistry showed that high-dose MaR1 attenuated LPS-induced increases in pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), chemokines [keratinocyte chemokine, monocyte chemoattractant protein-5, macrophage inflammatory protein (MIP)-1α and MIP-1γ], pulmonary myeloperoxidase activity and neutrophil infiltration in the lung tissues. Consistent with these observations, flow cytometry and Western blotting indicated that MaR1 down-regulated LPS-induced neutrophil adhesions and suppressed the expression of intercellular adhesion molecule (ICAM)-1, P-selection and CD24. CONCLUSIONS AND IMPLICATIONS: High-dose MaR1 mitigated LPS-induced lung injury in mice by inhibiting neutrophil adhesions and decreasing the levels of pro-inflammatory cytokines.

[Effects and mechanism of berberine on the hypertensive renal injury rats induced by enriched high fat-salt-fructose diet].

OBJECTIVE: To study the effects of berberine on hypertensive renal injury model in rats fed by enriched high fat-salt-fructose diet . METHODS: hypertensive renal injury model was esteblished by feeding enriched high fat-salt-fructose diet for 8 weeks. On the basis of animal blood pressure, hypertensive rats were randomly divided into model group (10 rats, distilled water), captopril group (10 rats,25 mg/kg), berberine high dose group (10 rats, 300 mg/kg) and low dose group (10 rats, 100 mg/kg). These rats were fed by enriched high fat-salt-fructose diet and treated by intragastric administration with drugs for 4 weeks. And normal control group (10 rats) was set Blood pressure was determined at 0, 4, 8, 10, 12 weekend,and after 4 weeks of drugs treatment, getting urine to determine urine protein, taking blood serum to determine blood urea nitrogen, serum creatinine,GHb,MDA and activity of SOD. The content of H2O2 and GSH-Px and activity of CAT in kidney tissues were determined also. RESULTS: Compared with normal control group, blood pressure, urine protein, blood urea nitrogen, serum creatinine and MDA and GHb in serum of model rats obviously increased (P < 0.01), the activity of SOD decreased (P < 0.01), higher content of H2O2 and lower content of GSH-Px and activity of CAT (P < 0.01) in the kidney tissues. Treated with berberine for 4 weeks, elevated blood pressure and heightened levels of urine protein, blood urea nitrogen and serum creatinine in model rats were depressed significantly (P < 0.01), and elevated the activity of SOD, lowed the levels of MDA and GHb in blood serum (P < 0.01). At the same time, berberine increased the activities of GSH-Px and CAT (P < 0.01) and slightly lowed the content of H2O2 in the kidney tissues. CONCLUSION: Berberine has protecting effects on the hypertensive renal impairment model rats fed by enriched high fat-salt-fructose diet, which are concerned with elevated antioxidant capability in body and kidney tissues.

[Cloning and characterization of CAST transcript 2 and 4 in sheep].

As an endogenous inhibitor of the calpain system activated by Ca2+, calpastatin (CAST) plays a regulatory role in muscle proteolysis. Based on the bovine mRNA sequences, part of cDNA fragments of sheep CAST transcript 2 and 4 were obtained by RT-PCR. Bioinformatic analysis showed that sheep CAST transcript 2 was 4 358 bp in length with an open reading frame (ORF) 2 361 bp long and encoded 786 amino acids, while sheep CAST transcript 4 was 1 467 bp in length with 1 317 bp ORF encoding 438 amino acids. It was predicted that CAST type II contained four conserved domains and CAST type IV contained three conserved domains, and their secondary structures were rich in both hydrophobic regions and helical regions, with certain conserved phosphorylation sites and phosphorylation sites of protein kinase C (PKC). RT-PCR was conducted to analyze the expression patterns of CAST transcript 2 and transcript 4. CAST transcript 2 was ex-pressed in ten tissues detected while CAST transcript 4 only in testis.