Role of lifestyle factors in mediating the effect of educational attainment on bone mineral density: a Mendelian randomization study.

We performed two-step multivariable Mendelian randomization analysis to explore the mediating role of lifestyle factors in educational attainment (EA) and bone mineral density (BMD). Summary statistics from genome-wide association studies of European lineages were used. Coffee intake and processed-meat intake mediated the association between EA and BMD. PURPOSE: This study aimed to explore the causal relationship between educational attainment (EA) and bone mineral density (BMD), as well as the potential mediating roles of lifestyle factors in the expected EA-BMD relationship. By identifying modifiable lifestyle factors, we hope to provide relevant information to prevent osteoporosis or low BMD in the less educated population. METHODS: Using summary statistics from genome-wide association studies (GWAS) of major European lineages, one- and two-sample Mendelian randomization (MR) analyses were performed to estimate the association between EA (in the social sciences genetic association consortium (SSGAC) involving 766,345 individuals and in the UK Biobank (UKB) involving 293,723 individuals) and BMD (in the Genetic Factors for Osteoporosis Consortium involving 426,824 individuals selected from the UKB). The EA variable in both consortia were expressed by years of schooling completed. Two-step multivariable MR was used to assess the mediating roles of eight lifestyle-related factors (moderate-to-vigorous physical activity, watching television, computer using, smoking initiation, coffee intake, alcohol intake frequency, tea intake, and processed-meat intake) in the EA and BMD association, and the corresponding mediating proportion was calculated. Meta-analysis was used to present a pooled estimate. RESULTS: A total of 317 and 73 independent single-nucleotide polymorphisms (SNPs) of GWAS significance (P < 5.0 × 10-8) were selected as instrumental variables (IVs) for EA in the SSGAC and UKB, respectively. A total of 513 SNPs were selected as IVs for the BMD. The results of one- and two-sample MR revealed that the genetically predicted BMD increased by 0.094 and 0.047 g/cm2, respectively, in response to each SD increment of genetically predicted schooling years. Among the eight candidate mediators, coffee intake and processed-meat intake were potential mediators revealed by the two-step multivariable MR analysis, mediating 26.87% and 23.92% of EA's effect on BMD, respectively. Meta-analysis showed consistent findings. Results of sensitivity analysis indicated the robustness of our findings. CONCLUSION: We elucidated the causal protective effect of EA on BMD and the mediating roles of coffee intake and processed-meat intake. Intervening with these factors can potentially reduce the burden of bone density loss or osteoporotic fractures among the less educated population.

A novel prognostic index for diffuse large B-cell lymphoma combined baseline metabolic tumour volume with clinical and pathological risk factors.

OBJECTIVES: This study aimed to develop a novel prognostic index integrating baseline metabolic tumour volume (MTV) along with clinical and pathological parameters for diffuse large B-cell lymphoma (DLBCL). METHODS: This prospective trial enrolled 289 patients with newly diagnosed DLBCL. The predictive value of novel prognostic index was compared with Ann Arbor staging and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). We used the concordance index (C-index) and a calibration curve to determine its predictive capacity. RESULTS: Multivariate analysis revealed high MTV (>191 cm 3 ), Ann Arbor stage (III-IV) and MYC/BCL2 double expression lymphoma (DEL) to be independently associated with inferior progression-free survival (PFS) and overall survival (OS). Ann Arbor stage and DEL could be stratified by MTV. Our index, combining MTV with Ann Arbor stage and DEL status, identified four prognostic groups: group 1 (no risk factors,), group 2 (one risk factor), group 3 (two risk factors), and group 4 (three risk factors). The 2-year PFS rates were 85.5, 73.9, 53.6, and 13.9%; 2-year OS rates were 94.6, 87.0, 67.5, and 24.2%, respectively. The C-index values of the novel index were 0.697 and 0.753 for PFS and OS prediction, which was superior to Ann Arbor stage and NCCN-IPI. CONCLUSION: The novel index including tumour burden and clinicopathological features may help predict outcome of DLBCL (clinicaltrials.gov identifier: NCT02928861).

Neuroprotective and antioxidant activities of different polarity parts of the extracts of the Ginkgo biloba leaf and Zingiber officinale rhizome from Yongzhou.

In order to make better use of the two local dominant plant resources of Ginkgo biloba and Zingiber officinale from Yongzhou in Hunan province, the in vitro neuroprotective and antioxidant activities of extracts from the G. biloba leaf and Z. officinale rhizome, and the correlation between these two kinds of activities, were analyzed. The in vivo effects of these two plant extracts on aged mice blood physiology and central neuron cell activity were then determined after continuous gavage with the best polarity part at different concentrations (2, 4, 8 mg/ml). The results showed that the cell survival rate and superoxide dismutase (SOD) activity of the induced injury central neurons increased, although the malondialdehyde (MDA) content decreased gradually with the extract concentrations increasing in a certain range. Different polarity parts performed differently, even though they had the same concentration, with G. biloba always performing better than the Z. officinale rhizome at the same concentration and polarity. The order of G. biloba extract from superior to inferior was ethanol, ethyl acetate, n-butanol, chloroform, water, and petroleum ether (except that the petroleum ether part performed slightly better than the water part at 0.4 and 0.5 mg/ml), while the order of Z. officinale rhizome extract from superior to inferior was ethanol, chloroform, n-butanol, ethyl acetate, water, and petroleum ether. These two plant extracts demonstrated good in vitro effect against oxygen free radicals; the scavenging rate of superoxide free radicals had a significant positive correlation with the cell survival rate. The in vivo central nerve cell activity and SOD, glutathione peroxidase (GSH-PX) activity in aged mice blood serum increased while the MDA content decreased with treatment with these two extracts (p < 0.05). There were no significant changes in the number of leukocytes, lymphocytes, red blood cells, hemoglobin content, blood urine nitrogen, uric acid, creatinine, and the enzyme activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) (p > 0.05). G. biloba had a better in vivo effect than Z. officinale rhizome even though their concentration and polarity part were same. These results could provide some references for better development of these two plant extracts from Yongzhou in the field of neuroprotection.

Selenium in selenium-rich rice sold in China and risk assessment.

Selenium-rich rice samples of 52 brands were bought from supermarkets on line in China and analysed for Se with ICP-MS. The Se concentration of Se-rich rice in China ranged from 0.012 ± 0.001 to 0.558 ± 0.057 mg/kg with an average of 0.090 ± 0.092 mg/kg. Rice samples with Se concentrations below 0.04 mg/kg accounted for 36.5% of the total samples. Se concentrations between 0.04 and 0.3 mg/kg accounted for 61.6%. Taking the upper tolerable limit of 400 µg/d as the risk standard, the risk of selenium intake by selenium-rich rice was low and the risk index was far less than 100%. With the upper intake limit of 100 µg/d and the adequate intake of 70 µg/d as the risk standard, the maximum intake risk index was higher than 100%, indicating a certain risk in the consumption of selenium-rich rice.

Anti-aging effects of the fermented anthocyanin extracts of purple sweet potato on Caenorhabditis elegans.

Anthocyanins have anti-inflammatory, anticarcinogenic and antioxidant properties and anti-aging effects as well as potential application as pigments. The metabolism of anthocyanins in fermented food has attracted increasing attention. However, the effect of lactic acid bacteria (LAB) fermentation on its anti-aging activity remains mostly unknown. The current study aimed to investigate the compositions, antioxidant activities and anti-aging effect of fermented purple sweet potato anthocyanins (FSPA) on aging Caenorhabditis elegans compared to raw purple sweet potato anthocyanins (PSPA). Results showed that anthocyanins were degraded into more bioavailable phenolic acids by Weissella confusa fermentation. PSPA and FSPA can extend the lifespan of C. elegans by 26.7% and 37.5%, respectively, through improving the activity of antioxidant enzymes as well as decreasing MDA content, ROS levels and lipofuscin accumulation. Pretreatment of the worms with PSPA and FSPA induced their potential to resist to thermal tolerance and oxidative stress, and FSPA exerted a higher anti-stress effect than PSPA. Moreover, FSPA supplementation upregulated the mRNA expressions of genes daf-16, hsp-16.2, sir-2.1, skn-1 and sod-3 and downregulated the expression of daf-2 in the nematodes, whereas PSPA only induced the increase in the expressions of sir-2.1, skn-1 and sod-3. Overall, FSPA can improve stress resistance and extend the lifespan of C. elegans by both insulin/IGF-1 signaling pathway and dietary restriction pathway, providing a theoretical basis for the application of PSPA in fermented food as functional pigments.

Preparation and characterization of D. opposita Thunb polysaccharide-zinc inclusion complex and evaluation of anti-diabetic activities.

In the present work, Dioscorea opposita Thunb polysaccharide-zinc (DPS-zinc) inclusion complex was synthesized for the first time and its anti-diabetes activities against Streptozotocin (STZ)-induced diabetic rats were assayed. The detail structural and morphological analysis of as-prepared DPS-zinc complex was done by using different spectroscopic and microscopic methods. The pharmacological study revealed that DPS-zinc presented a potent hypoglycemic effect on STZ-induced diabetic rats, decreased the glucose and insulin levels, reduced malondialdehyde (MDA) contents and increased SOD and T-AOC activities significantly in liver. The levels of T-CHO, TG and LDL-C in serum were dramatically decreased while HDL-C level was increased with the treatment of proposed inclusion complex. In brief, DPS-zinc could be considered as a potential candidate for developing an ingredient of functional foods for zinc supplements with the hypoglycemic action.

Pharmacokinetic and tissue distribution profile of curculigoside after oral and intravenously injection administration in rats by liquid chromatography-mass spectrometry.

Curculigoside has an extensive pharmacological activity, including estrogen-like, improving sexual behavior, antiosteoporotic, antioxidant, immunomodulatory and neuroprotective effects. However, few investigations have been conducted about the pharmacokinetics and tissue distribution of curculigoside to better understand its behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid chromatography with mass spectrometry (HPLC-MS) method was established and validated for the quantification of curculigoside in rat plasma and tissue samples. Biological samples were processed with methanol precipitation, and naringin was used as the internal standard. Chromatographic separation was performed on an Agilent XDB-C18 chromatography column (3.0mm×50mm, 1.8µm) with a mobile phase consisting of acetonitrile and 0.1% formic acid. Quantification was performed by selected ion monitoring with m/z 511.1 [M+HCO2](-) for curculigoside and m/z 579.1 [M-H](-) for the internal standard. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of curculigoside in rats. Non-compartmental pharmacokinetic parameters indicated that curculigoside had rapid distribution, extensive tissue uptake, and poor absorption into systemic circulation. The values of absolute bioavailability were 0.38%, 0.22% and 0.27% for oral doses of 100, 200 and 400mg/kg, respectively. The results of the tissue distribution study suggested that curculigoside was distributed into the heart, lung, spleen, intestine, stomach, kidney, thymus, liver, brain, testis, and bone marrow after oral administration of 150mg/kg. In conclusion, the present study may provide a material basis for study of the pharmacological action of curculigoside, and meaningful insights into further study on clinical application.

Is acupuncture a placebo therapy?

Complementary therapies such as acupuncture are suggested to have enhanced placebo effects. Numerous high quality randomized controlled trials found that acupuncture is no better than its placebo control; however, patients in both real and sham acupuncture groups report clinically meaningful symptom improvements. A possible interpretation of these trials is that acupuncture acts entirely by engaging placebo mechanisms. This article provides further evidence supporting that acupuncture might be a potent placebo, and explains how to address major concerns following this suggestion.

[Research progress of phytoestrogens-like chemical constituents in natural medicines].

Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.

Medicinal plants of genus Curculigo: traditional uses and a phytochemical and ethnopharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: In the genus Curculigo, Curculigo orchioides Gaertn, Curculigo capitulata (Lour) O. Ktze and Curculigo pilosa (Schumach. & Thonn.) Engl are often used in traditional medicine. Curculigo orchioides is used for the treatment of impotence, limb limpness, arthritis of the lumbar and knee joints, and watery diarrhea in traditional Chinese medicine, and also used as a potent immunomodulator and aphrodisiac in the Ayurvedic medical system. Curculigo capitulata is used for the treatment of consumptive cough, kidney asthenia, impotence and spermatorrhea, hemorrhoids, asthma, jaundice, diarrhea, colic and gonorrhea in traditional Chinese and India medicine, and to treat urinary tract infection, acute renal pelvis and nephritis, nephritis-edema, cystitis, nephrolithiasis, hypertension and rheumatic arthritis in traditional Dai medicine. Curculigo pilosa are applied to treat gastrointestinal and heart diseases in Africa. AIM OF THE REVIEW: This review aims to exhibit up-to-date and comprehensive information about traditional uses, phytochemistry, pharmacology and toxicology of medicinal plants in the genus Curculigo, and has an insight into the opportunities for the future research and development of Curculigo plant. METHODS: A bibliographic investigation was performed by analyzing the information available on Curculigo plant from worldwide accepted scientific databases (Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo). Furthermore, information also was obtained from some local and foreign books on ethnobotany and ethnomedicines. RESULTS: Curculigo orchioides, Curculigo capitulata and Curculigo pilosa have been used as traditional medicine to treat kinds of diseases such as impotence, limb limpness, gastrointestinal and heart diseases, etc. Phytochemical investigation of eight species of the genus Curculigo has resulted in identification of more than 110 compounds. The content of curculigoside is used as an indicator to evaluate the quality of rhizome of Curculigo orchioides. The medicinal plants have showed a wide spectrum pharmacological activities, including adaptive, immunostimulatory, taste-modifying and sweet-tasting, antioxidant, mast cell stabilization, antihistaminic and antiasthmatic, hepatoprotective and neuroprotective activity. Toxicological test indicated that Curculigo orchioides at the dose of 120 g/kg after administrating rats for 180 days may cause injury of liver and kidney. CONCLUSION: The medicinal plants of genus Curculigo have emerged as a good source of the traditional medicines. Some uses of these plants in the traditional medicines have been validated by pharmacological investigation. However, the mechanism of their actions should be further elucidated; the particular constituent responsible for toxicity should be isolated and identified, and the target tissue and mechanism of toxic ingredients also deserve to be further investigated; more reference substances should be prepared, and sophisticated analytical technologies should be developed to comprehensively assess the quality of Curculigo herbs. These investigations will be helpful for further utilization of the plants of genus Curculigo.

The Arabidopsis LFR gene is required for the formation of anther cell layers and normal expression of key regulatory genes.

The anther is the male reproductive organ in flowering plants. Although some genes were reported to be involved in anther development, the molecular mechanisms underlying the transcriptional regulation of these genes is unclear. lfr-2 (leaf and flower related-2), the null allele of Arabidopsis thaliana LFR (LEAF AND FLOWER RELATED), was male-sterile. The anthers of lfr-2 plants were defective in sporogenous cell formation, tapetum development, and pollen development. In agreement with these phenotypes, expression studies showed that LFR was expressed in all cell layers of the anther, and that expression was particularly strong in the tapetal cells and pollen grains. Quantitative RT-PCR analysis revealed that LFR is required for the normal transcription of some anther development-related genes, such as AMS, CALS5, and DYT1, MS1 and MS2, and ROXY2. Genetic analysis showed that SPL was epistatic to LFR while LFR was epistatic to DYT1. We propose that LFR may be a crucial component in the regulation of a genetic network that modulates anther development.