New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit ß-Amyloid42 Production and Phospho-Tau (Thr217).

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C (1-3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1-3 all reduce Aß42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3ß-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.

Combination of Chinese medicinal formulas and chemotherapy for triple-negative breast cancer strengthens body resistance to eliminate pathogenic factors.

BACKGROUND: To evaluate the efficacy and safety of strengthening the body's resistance to eliminate pathogenic factors in Chinese medicinal formulas combined with chemotherapy (hereafter referred to as combined therapy [CT]) in triple-negative breast cancer. METHODS: By searching the 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, Chinese Academic Journal, Wanfang Database, and Chinese Science and Technology Journal, from the beginning of the establishment to April 2022 to identify eligible randomized controlled trial studies. RESULTS: The meta-analysis showed that compared with chemotherapy, CT can effectively improve the objective remission rate (risk ratio [RR]: 1.39; 95% confidence interval [CI]: 1.28, 1.52; P < .00001, I2 = 3%), reduce the recurrence rate (RR: 0.33; 95% CI: 0.14, 0.78; P = .01, I2 = 0%) metastasis rate (RR: 0.48; 95% CI: 0.31, 0.73; P = .0006, I2 = 0%) and the incidence of toxic and side reactions, lower tumor marker levels, regulated T lymphocyte subset changes, and increased average progression-free survival (standardized mean difference: 2.78; 95% CI: 1.41, 4.14; P < .0001, I2 = 97%), and improve the quality of life (RR: 1.55; 95% CI: 1.21, 1.99; P = .0005, I2 = 52%). CONCLUSION: This study suggests that CT appears to be an effective and safe treatment approach. Although this conclusion requires further confirmation owing to insufficient quality of the included trials.

Efficacy and Safety of Traditional Chinese Medicine in the Treatment of Immune Infertility Based on the Theory of "Kidney Deficiency and Blood Stasis": A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of traditional Chinese medicine (TCM) therapy of tonifying kidney and activating blood circulation (TKABC) based on the theory of "kidney deficiency and blood stasis" for the treatment of immune infertility. METHODS: Six electronic databases, including the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, Wanfang Data, and VIP information database, were searched from inception to January 2021 to identify eligible studies of randomized controlled trials (RCTs). The primary outcome measurements were the total effective rate and pregnancy rate, and the secondary outcome measurements included the negative conversion rate of serum antibodies and the incidence of adverse effects. The quantitative synthesis was performed using the Review Manager 5.3 software. The chi-square statistic and I 2 statistic were employed to investigate statistical heterogeneity. The fixed-effects model was used for a low heterogeneity (I 2 < 50%), and the random-effects model was applied if heterogeneity was moderate (50% < I 2 < 75%). Funnel plots were used to evaluate potential reporting bias when more than ten eligible studies were included. RESULTS: Thirteen RCTs involving 1298 patients with immune infertility of kidney deficiency and blood stasis were included. Compared with conventional group, TCM TKABC therapy showed a significant improvement on the total effective rate (RR: 1.38; 95% CI: 1.30,1.47; and I 2 = 0%), pregnancy rate (RR: 2.04; 95% CI: 1.73, 2.40; and I 2 = 30%), negative conversion rates of AsAb (RR: 1.42; 95% CI: 1.12,1.79; and I 2 = 62%), AEmAb rates (RR: 1.21; 95% CI: 1.04,1.41; and I2 = 0%), and AhCGAb with less adverse effects (RR: 0.24; 95% CI: 1.73, 2.40; and I 2 = 55%). However, the negative conversion rate of AoAb and ACAb showed no significant statistical difference. CONCLUSIONS: Our review suggests that TCM TKABC therapy based on the theory of kidney deficiency and blood stasis appears to be an effective and safe approach for patients with immune infertility. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with more well-designed and high-quality multicenter RCTs.

Molecular Mechanism of Puerarin Against Diabetes and its Complications.

Puerarin is a predominant component of Radix Puerarin. Despite its anti-tumor and anti-virus effects and efficacy in improving cardiovascular or cerebrovascular diseases and preventing osteoporosis, it has been shown to protect against diabetes and its complications. This review summarizes the current knowledge on Puerarin in diabetes and related complications, aiming to provide an overview of antidiabetic mechanisms of Puerarin and new targets for treatment.

Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

SCOPE: This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese. METHODS AND RESULTS: Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected. Ferritin concentrations were higher in men than women (201.55 ± 3.6 versus 80.46 ± 1.64 ng/mL, p < 0.0001). The prevalences of MetS, diabetes, obesity, and overweight were 8.05, 8.97, 4.67, 25.88% among men and 14.23, 6.58, 5.81, 26.82% among women, respectively. Elevated ferritin concentrations were associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p < 0.0001). Serum ferritin concentrations increased gradually with aging among women. The inverted U-shaped association between serum ferritin and age was observed among men. Elevated concentration of ferritins were significantly related with higher risk of MetS (p < 0.0001), obesity (p = 0.010), overweight (p < 0.0001), and diabetes (p < 0.0001) among men, but not among women. CONCLUSION: There was a gender difference in associations between ferritin and MetS, obesity, and diabetes in Chinese adults. Further evaluations of the variation in gender on these associations are warranted to understand the mechanisms behind gender differences.

Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons.

Ghrelin, a 28-amino acid brain-gut peptide expressed in periphery tissues and the central nervous system, has been demonstrated to increase insulin sensitivity in adipocytes. Recent data have indicated that insulin resistance exists in the brain and is related to Alzheimer's Disease (AD). The aim of this study was to investigate whether ghrelin increased high glucose-induced hippocampal neuron insulin sensitivity, and further modulated tau phosphorylation. Hippocampal neurons were cultured in concentrations of 25 mM and 75 mM glucose. The effect of ghrelin on hippocampal neuronal insulin sensitivity was detected by [(3)H]-2-deoxy-D-glucose uptake. The expression of Akt, glycogen synthase kinase-3beta (GSK-3beta) and tau phosphorylation was determined via Western blotting. Culturation in 75 mM glucose resulted in decreased neuronal glucose uptake and an increase in the level of tau phosphorylation at Ser 199. In neurons treated with ghrelin for 1 h, neuronal glucose uptake was increased and tau hyperphosphorylation was improved. Ghrelin activated Akt and GSK-3beta phosphorylation, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin eliminated ghrelin's effect on neuronal glucose uptake and tau phosphorylation. This study demonstrated that ghrelin increased insulin-stimulated neuronal glucose uptake in 25 mM or 75 mM glucose, raised insulin sensitivity, improved insulin resistance and decreased tau abnormal phosphorylation via the PI3-K/Akt-GSK pathway. Ghrelin is a potential new medicine in the treatment of AD.

[Investigation and analysis of neonate deformity in water arsenic exposure areas].

OBJECTIVE: To explore the level and feature of neonate deformity in water arsenic exposure areas, as to finding out an evidence for the study and prevention of the arsenic exposure. METHODS: The birth situation of neonate was surveyed from 1998 to 2004 in water arsenic exposure areas according to cross-sectional survey. The results were classified in accordance with ICD-10 and common surveillance of china. The population of Shanyin County served as the common people and the data were analyzed by SPSS 11.5 for windows. RESULTS: The neonates surveyed were 2467 cases. There were 49 neonates deformity found in this investigation, giving a neonate deformity rate of 198.62 per 10,000 cases, which was shown significantly higher in water arsenic exposure areas than in the normal (U = 3.23, P < 0.01), with types of nervous system deformity, limbs deformity and congenital heart disease as in system classification. There was no significant difference of deformity rate in different sex neonates (chi2 = 0.32, P > 0.05). CONCLUSION: The drinking high-arsenic water over a long period of time should be a risk factor of neonate deformity. Prevention and treatment of endemic arsenic exposure should be urgently needed.

[Studies on absorption kinetics of paeonol and paeonol-beta-CD in rat's intestines].

To explore the absorption mechanism of paeonol-beta-CD from various intestinal segments and offer biopharmaceutics data for paeonol new dosage form. The absorption kinetics and permeability rate consatants were investigated by the in situ perfusing method in rats. The absorption of the drug conforms to the firt-order kinetics and passive transport mechanism . The results indicate that paeonol-beta-CD absorption mechanism wasn't change.

Arsenic and fluoride exposure in drinking water: children's IQ and growth in Shanyin county, Shanxi province, China.

BACKGROUND: Recently, in a cross-sectional study of 201 children in Araihazar, Bangladesh, exposure to arsenic (As) in drinking water has been shown to lower the scores on tests that measure children's intellectual function before and after adjustment for sociodemographic features. OBJECTIVES: We investigated the effects of As and fluoride exposure on children's intelligence and growth. METHODS: We report the results of a study of 720 children between 8 and 12 years of age in rural villages in Shanyin county, Shanxi province, China. The children were exposed to As at concentrations of 142 +/- 106 microg/L (medium-As group) and 190 +/- 183 microg/L (high-As group) in drinking water compared with the control group that was exposed to low concentrations of As (2 +/- 3 microg/L) and low concentrations of fluoride (0.5 +/- 0.2 mg/L). A study group of children exposed to high concentrations of fluoride (8.3 +/- 1.9 mg/L) but low concentrations of As (3 +/- 3 microg/L) was also included because of the common occurrence of elevated concentrations of fluoride in groundwater in our study area. A standardized IQ (intelligence quotient) test was modified for children in rural China and was based on the classic Raven's test used to determine the effects of these exposures on children's intelligence. A standardized measurement procedure for weight, height, chest circumference, and lung capacity was used to determine the effects of these exposures on children's growth. RESULTS: The mean IQ scores decreased from 105 +/- 15 for the control group, to 101 +/- 16 for the medium-As group (p < 0.05), and to 95 +/- 17 for the high-As group (p < 0.01). The mean IQ score for the high-fluoride group was 101 +/- 16 and significantly different from that of the control group (p < 0.05). Children in the control group were taller than those in the high-fluoride group (p < 0.05); weighed more than the those in the high-As group (p < 0.05); and had higher lung capacity than those in the medium-As group (p < 0.05). CONCLUSIONS: Children's intelligence and growth can be affected by high concentrations of As or fluoride. The IQ scores of the children in the high-As group were the lowest among the four groups we investigated. It is more significant that high concentrations of As affect children's intelligence. It indicates that arsenic exposure can affect children's intelligence and growth.

Epidemiological evaluations of the efficacy of slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and animals.

To assess the epidemiological efficacy of type SRP III slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and livestock, praziquantel-medicated bars were implanted subcutaneously in over 90% of dogs in villages in north Xinjiang, China, where cystic echinococcosis is highly endemic. After implantation, infection rate of Echinococcus granulosus in dogs, specific antibodies in children and prevalence of echinococcosis in one-year-old lambs were observed for 3 years. Coproantigen of E. granulosus was positive in 41.2% of the dogs at the start of experiment. In the second and third year after medicated-bar implantation, coproantigen was undetectable in any dogs examined, while 3.0% of dogs were positive at the end of the fourth year. The antibody positive rate in 7-year-old pupils, that was 41.2% before the experiment, declined gradually and it was 5.4% in the fourth year, while children in the non-intervention control area showed 30.6% seropositivity. The prevalence of hydatid disease in children aged 7-16 years also declined significantly. The prevalence of hydatidosis in lambs one year of age was 44.8% in the first year, dropping to 10.7% in the fourth year, while in the non-intervention control area the level of infection was 46.4%. These results demonstrated not only that the slow released praziquantel-medicated bars efficiently blocked reinfection in dogs at least for 2 years, but also the measure was effective in preventing transmission of cystic echinococcosis to both man and livestock.