PMID: 

PLoS One. 2019 ;14(5):e0217223. Epub 2019 May 31. PMID: 31150426

Abstract Title: 

Fruit and vegetable intake and bones: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: Although intake of fruits and vegetables seemed to have a protective effect on bone metabolism, its effect on fractures remains uncertain.METHODS: A systematic review of randomized controlled trials (RCTs) and cohort studies (PROSPERO: CRD42016041462) was performed. RCTs and cohort studies that evaluated the combined intake of fruits and vegetables in men and women aged over 50 years were included. We considered fractures as a primary outcome measure. Changes in bone markers were considered as secondary outcomes. The search strategy included the following descriptors: fruit, vegetables, vegetable products, bone and bones, bone fractures, postmenopausal osteoporosis, and osteoporosis. PubMed, Embase, and Cochrane Library were the databases used. The appraisal of the studies was performed by two independent reviewers, and discussed and agreed upon by both examiners. The data extracted from the RCTs and cohort studies were summarized separately. The risks of fractures were combined across studies using random models. Bone resorption marker (CTx) was summarized with standardized mean differences. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate the strength of recommendations.RESULTS: Of the 1,192 studies screened, 13 articles were included in the systematic review and 10 were included in the pooled analysis (6 cohort studies and 4 RCTs). The six cohort studies included in the meta-analysis included a population of 225,062. The pooled hazard ratio (HR) (95% confidence interval (CI)) of the hip in five studies was 0.92 (0.87, 0.98). Its heterogeneity was moderate (I2 = 55.7%, p = 0.060), GRADE (⊕⊕⊕O). Two cohort studies evaluated the risk of any fracture; the HR was 0.90 (95% CI: 0.86-0.96), with aheterogeneity of 24.9% (p = 0.249, GRADE (⊕⊕⊕O)). There was no association between the bone resorption marker CTx and 3 months of fruit and vegetable intake evaluated by four RCTs, GRADE (⊕⊕O O).CONCLUSION: There was an association between the increase of at least one serving of fruits and vegetables per day and decreases in the risk of fractures. The level of evidence for this association is moderate.

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PMID: 

J Nutr. 2019 Jun 4. Epub 2019 Jun 4. PMID: 31162586

Abstract Title: 

Intake of Vegetables and Fruits Through Young Adulthood Is Associated with Better Cognitive Function in Midlife in the US General Population.

Abstract: 

BACKGROUND: Vegetables and fruits (VF) may differentially affect cognitive functions, presumably due to their various nutrient contents, but evidence from epidemiologic studies is limited.OBJECTIVES: The aim of this study was to examine the long-term association between VF intakes, including VF subgroups, in young adulthood and cognitive function in midlife.METHODS: A biracial cohort of 3231 men and women aged 18-30 y at baseline in 1985-1986 were followed up for 25 y in the Coronary Artery Risk Development in Young Adults Study. Diet was measured at baseline, and in examination years 7 and 20. Cognitive function was assessed at examination year 25 through the use of 3 tests: the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test. The mean differences (MDs) with 95% CIs in cognitive scores across intake categories were estimated through the use of the multivariable-adjusted general linear regression model.RESULTS: Excluding potatoes, intake of whole vegetables was significantly associated with a better cognitive performance after adjustment for potential confounders in all 3 cognitive tests (quintile 5 compared with quintile 1-RAVLT, MD: 0.33; 95% CI: 0.01, 0.64; P-trend = 0.08; DSST, MD: 2.84; 95% CI: 0.93, 4.75; P-trend 

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PMID: 

BMC Public Health. 2019 Jun 7 ;19(1):707. Epub 2019 Jun 7. PMID: 31174509

Abstract Title: 

Coronary heart disease and stroke disease burden attributable to fruit and vegetable intake in Japan: projected DALYS to 2060.

Abstract: 

BACKGROUND: Fruit and vegetable consumption was considered a protective effect against cardiovascular and cerebrovascular diseases (CVDs). This study aimed to project the reduction in the CVD burden under different scenarios of increased fruit and vegetable intake in Japan by 2060.METHODS: Population attributable fractions (PAF) were calculated by gender and age in 2015. The projection considered five scenarios for 2015, 2030, 2045, and 2060: 1) a baseline of no changes in intake; 2) a moderate increase in fruit intake (extra 50 g/day or 1/2 serving); 3) an high increase in fruit intake (extra 100 g/day or 1 serving); 4) a moderate increase in vegetable intake (extra 70 g/day or 1 serving); and 5) an high increase in vegetable intake (extra 140 g/day or 2 servings). Potentially preventable disability-adjusted lifeyears (DALYs) for CVDs were estimated for each scenario. Monte Carlo simulations were performed to calculate the 95% confidence intervals of the estimates.RESULTS: Across all age groups, men had a higher daily vegetable intake than women (292.7 g/d > 279.3 g/d) but a lower daily fruit intake (99.3 g/d 

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PMID: 

Mol Med Rep. 2019 Aug ;20(2):1321-1332. Epub 2019 Jun 5. PMID: 31173225

Abstract Title: 

Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways.

Abstract: 

Artesunate (ART) is a semi‑synthetic derivative of artemisinin used in the treatment of patients with malaria, which has also been reported to have immunoregulatory, anticancer and anti‑inflammatory properties. The aim of the present study was to investigate the possible beneficial effects of ART on ulcerative colitis (UC) rats and to detect the possible mechanisms underlying these effects. A UC rat model was established using dextran sulfate sodium (DSS). Rats were randomly divided into the following groups: Normal control, UC model group, UC rats treated with a low, medium or high dose of ART (10, 30 and 50 mg/kg/day, respectively), and the positive control group (50 mg/kg/day 5‑aminosalicylic acid). The damage status of colonic mucosal epithelial tissue was investigated by hematoxylin and eosin staining, and then the weight, colon length and disease activity index (DAI) were measured. Western blottingand reverse transcription‑quantitative polymerase chain reaction analysis were used to detect the levels of cytokines associated with UC and proteins associated with Toll‑like receptor 4 (TLR4)‑nuclear factor (NF)‑κB pathway. ELISA was also performed to measure the levels of inflammatory cytokines. In addition, the viability and infiltration of RAW264.7 cells were examined using Cell Counting Kit‑8 and Transwell assays. The results demonstrated that treatment with ART significantly alleviated the UC symptoms induced by DSS in the rat model, lowered the DAI, ameliorated pathological changes, attenuated colon shortening, inhibited the levels of pro‑inflammatory mediators and myeloperoxidase activity, and increased hemoglobin expression. Additionally, inflammatory and apoptotic markers were found to be significantly downregulated following treatment with ART in UC rats and RAW264.7 cells. To the best of our knowledge, the present study is the first to demonstrate that ART exerts anti‑inflammatory effects via regulating the TLR4‑NF‑κB signaling pathway in UC.

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PMID: 

Front Pharmacol. 2019 ;10:685. Epub 2019 Jun 14. PMID: 31258481

Abstract Title: 

Artesunate, an Anti-Malaria Agent, Attenuates Experimental Osteoarthritis by Inhibiting Bone Resorption and CD31EmcnVessel Formation in Subchondral Bone.

Abstract: 

Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-β/Smad2/3 signaling. Additionally, ART abrogated CD31Emcnvessel formationdownregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31Emcnvessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.

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PMID: 

Phytomedicine. 2019 May 21 ;63:152968. Epub 2019 May 21. PMID: 31280140

Abstract Title: 

Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling.

Abstract: 

BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated.PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA.METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action.RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation.CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.

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PMID: 

FASEB J. 2019 Jul ;33(7):8241-8248. Epub 2019 Mar 27. PMID: 30916998

Abstract Title: 

Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells.

Abstract: 

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune-mediated destruction of insulin-producingβ cells. Recent studies showed that in addition to malaria, artemisinin and its derivative, artesunate (AS), could alleviate several autoimmune diseases. However, whether AS has a role in the prevention or treatment of T1D is still unknown. Therefore, in this study we administrated AS or DMSO in the drinking water of nonobese diabetic (NOD) mice, a mouse model of T1D. We found that AS administration significantly prevented the incidence of T1D. The frequency of IL-4-producing CD4single-positive T cells and CD8T cells was significantly elevated, and IFN-γ-producing T cells were reduced in the spleen and pancreatic lymph nodes. In the pancreas, the skewing to IL-4-producing T cells was also observed. In addition, more regulatory T cells were found in the pancreas. mRNA levels of proinflammatory cytokines, including TNF-α and IL-6, were decreased.In addition, AS administration promoted the functional maturity of β cells. Our findings demonstrate that AS administration can prevent T1D in NOD mice mainly by reducing autoimmune T cells and increasing protective T cells. Our data constitute the first functional study of AS in T1D, which may provide a new rationale for future translational studies.-Li, Z., Shi, X., Liu, J., Shao, F., Huang, G., Zhou, Z., Zheng, P. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells.

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PMID: 

Braz J Med Biol Res. 2019 ;52(5):e7992. Epub 2019 Apr 29. PMID: 31038546

Abstract Title: 

Artesunate promotes Th1 differentiation from CD4+ T cells to enhance cell apoptosis in ovarian cancer via miR-142.

Abstract: 

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosisin ovarian cancer.

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PMID: 

Am J Clin Nutr. 2019 Jul 13. Epub 2019 Jul 13. PMID: 31301130

Abstract Title: 

Improving fruit and vegetable intake attenuates the genetic association with long-term weight gain.

Abstract: 

BACKGROUND: Whether changes in fruit and vegetable intake can modify the effect of genetic susceptibility to obesity on long-term changes in BMI and body weight are uncertain.OBJECTIVE: We analyzed the interactions of changes in total and specific fruit and vegetable intake with genetic susceptibility to obesity in relation to changes in BMI and body weight.METHODS: We calculated a genetic risk score on the basis of 77 BMI-associated loci to determine the genetic susceptibility to obesity, and examined the interactions of changes in total and specific fruit and vegetable intake with the genetic risk score on changes in BMI and body weight within five 4-y intervals over 20 y of follow-up in 8943 women from the Nurses' Health Study (NHS) and 5308 men from the Health Professionals Follow-Up Study (HPFS).RESULTS: In the combined cohorts, repeated 4-y BMI change per 10-risk allele increment was 0.09 kg/m2 among participants with the greatest decrease in total fruit and vegetable intake and -0.02 among those with the greatest increase in intake (P-interaction 

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PMID: 

Food Chem Toxicol. 2019 Jul 10 ;132:110670. Epub 2019 Jul 10. PMID: 31301325

Abstract Title: 

Effects of bisphenol S, a major substitute of bisphenol A, on neurobehavioral responses and cerebral monocarboxylate transporters expression in mice.

Abstract: 

Bisphenol A has been restricted in a large variety of products. Bisphenol S (BPS) is its major substitute. Yet, the impacts of BPS on the central nervous system are unknown, especially in vulnerable populations like children. The aim of this study was to investigate the effects of BPS on behavioral performances and the expression of cerebral monocarboxylate transporters (MCTs). Male Swiss mice were exposed to BPS at 100 μg/kg in drinking water for 10 weeks. The protocol started after the lactation period, which is a sensitive period of early social-emotional development. Elevated T-maze and open field tests were used to measure respectively, anxiety-related and activity-related behaviors. Molecular expressionsof MCTs isoforms (MCT1, MCT2, MCT4) were determined in the frontal cortex. Data showed that BPS does not affect mRNA expression of MCTs. However, BPS decreases the number of entries into the open arms and the time spent on them for BPS-treated mice. These data reveal an anxiogenic effect of BPS. Forlocomotor activity and exploratory behavior levels, differences did not reach a statistically significant level in the BPS-exposed group. The effect of BPS on behavioral performances unravels a putative risk for psychopathology development in early childhood and calls for more attention.

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