Preference between Chinese and Western medicines for hypertension treatment: Evidences based on Chinese population aged ≥ 45 years.

Hypertension is one of the chronic diseases that threaten the health of the elderly population. This study aims to explore the treatment and medication preferences in Chinese elderly patients (≥45 years old) with hypertension, and to investigate the relevant influencing factors. A cross-sectional design was adopted. Utilizing the data from the public database CHARLS 2018, the factors influencing the treatment and medication preference among the elderly hypertensive patients were explored with multinomial logistic regression models. A total of 6588 hypertensive patients aged ≥ 45 years were included in this study, of which 5135 (77.94%) received treatment. Besides, 4939 (96.18%) chose oral medication, which was the most preferred treatment for these patients. The proportion of patients who chose "oral medication only" increased with age, but decreased with educational level and self-reported health. Patients with higher educational levels were more likely to choose other modalities of treatment. In particular, patients with better self-reported health were more willing to try traditional Chinese medication (TCM). Lower income group without medical insurance preferred to choose "Chinese medicine only." Patients aged ≥ 75 years, urban residents, and those with 2 or more chronic diseases were more willing to try combined Chinese and Western medicines. Patients' preference for TCM therapy was correlated positively with the provincial economic welfare factor, and negatively with the provincial medical and social welfare factors. During treatment of patients with hypertension, clinicians should pay attention to their preferences and formulate personalized regimens for them, in order to improve their compliance with treatment. Additionally, the government should steadily improve the local medical benefits, thereby facilitating the promotion and application of local TCM services.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.

Protective effects of Salvianolic acid B on rat ferroptosis in myocardial infarction through upregulating the Nrf2 signaling pathway.

Accumulating evidence has highlighted the role of ferroptosis, a novel type of programmed cell death involved in the pathological process of myocardial infarction (MI). However, the underlying mechanism of ferroptosis in mediating MI is complicated that needs to be further investigated. Salvianolic acid B (Sal B) extracted from the traditional Chinese medicine (TCM) herb Salvia miltiorrhiza possesses pharmacological function against MI, which provides us with a new direction to explore the effect of Sal B on ferroptosis after myocardial ischemic injury. In the present study, iron accumulation and expression levels of ferroptosis-related proteins in MI rats altered in a time-dependent manner. Importantly, treatment of ferroptosis inhibitors ferrostatin-1 (Fer-1) or deferoxamine (DFO) reversed typical changes of ferroptosis, including iron overload, lipid peroxide accumulation, mitochondrial damage, and specific expression levels of ferroptosis-related proteins, thereby alleviating myocardial injury in rats. Similar results were observed in Sal B-treated MI rats in a dose-dependent manner. In addition, NFE2-related factor 2 (Nrf2) was strongly activated by the treatment of Sal B. In vivo knockdown of Nrf2 in MI rats enhanced ferroptosis and damaged the protective effect of Sal B on MI. Furthermore, Sal B administration was unable to significantly reverse expression levels of target genes of Nrf2 that were associated with iron homeostasis and oxidative stress (e.g., HO-1, xCT, Gpx4, Fth1, and Fpn1) in MI rats after knockdown of Nrf2. Taken together, Sal B contributed to protecting MI by inhibiting ferroptosis via activating the Nrf2 signaling pathway.

Impact of DHA from Algal Oil on the Breast Milk DHA Levels of Lactating Women: A Randomized Controlled Trial in China.

Population research on the intervention of docosahexaenoic acid (DHA) supplementation in lactating women is in its infancy in China. This study investigated the effect of DHA supplementation on DHA concentrations in the breast milk of lactating women, and the intervention effect, with respect to different dietary patterns. In this trial, 160 healthy lactating women in Nanjing (30−50 days postpartum) were recruited and randomly divided into control (one placebo capsule of similar appearance per day) and supplement (one capsule with 200 mg of DHA from algal oil per day) groups for 8 weeks. Before and after the intervention, all subjects were asked to maintain basic information, maternal anthropometric parameters, breast milk (10−15 mL) sample collection, and a dietary survey using a food frequency questionnaire. The concentrations of DHA and other fatty acids in breast milk were detected using capillary gas chromatography. This study was completed by 137 subjects, with 60 in the control group and 77 in the supplement group. Compared with the DHA concentrations in the breast milk at enrollment, the absolute concentrations of the control group showed a significant decrease at the end of the trial (p = 0.037). In addition, after intervention, the absolute and relative DHA concentrations in the supplement group (10.07 mg/100 mL and 0.40%, respectively) were higher than those in the control group (7.57 mg/100 mL and 0.28%, respectively), being statistically significant (p = 0.012 and p = 0.001). Furthermore, the maternal diet in the supplement group was divided into four dietary patterns. Pattern 1 mainly included fruits and livestock meat. Pattern 2 was dominated by milk and its products, eggs, fish, shrimp and shellfish, and soybeans and its products. Pattern 3 chiefly comprised cereal and beans other than soybeans, potatoes, and nuts. Pattern 4 was high in poultry meat and low in cooking oils. The change in the absolute concentration of DHA in Pattern 3 was lower than that in other patterns (p < 0.05). In conclusion, DHA supplementation in lactating mothers increased breast milk DHA concentrations. The dietary pattern mainly characterized by cereal and beans other than soybeans, potatoes, and nuts may contribute to the poor intervention effect.

Association between dietary fatty acid patterns based on principal component analysis and fatty acid compositions of serum and breast milk in lactating mothers in Nanjing, China.

This study aimed to comprehensively analyze dietary fatty acids (FAs) to evaluate their association with FA compositions of maternal serum and breast milk and assess their effects on mothers and infants. Overall, 121 healthy lactating Chinese mothers at 30-50 days of postpartum were enrolled and instructed to complete a Food Frequency Questionnaire, together with venous blood and breast milk sample collections. Dietary FA patterns were derived by principal component analysis with varimax rotation. Serum and breast milk FA compositions were detected using capillary gas chromatography and presented as relative concentrations (weight percentage of total FAs, %). Daily energy intake, absolute intake of most nutrients, and percentage of energy intake provided by these nutrients significantly varied among the different dietary FA patterns. There were significant differences in serum polyunsaturated fatty acid (PUFA) levels (P = 0.011); in monounsaturated fatty acid and PUFA proportions in breast milk with respect to four patterns (P = 0.002 and P = 0.026, respectively); and in n-6 PUFA, n-3 PUFA, linoleic acid, γ-linolenic acid, α-linolenic acid, and docosahexaenoic acid levels in breast milk (P = 0.027, P = 0.007, P = 0.048, P = 0.034, P = 0.020, and P = 0.002, respectively). Furthermore, maternal weight retention and length-for-age z scores, weight-for-age z scores and head circumference-for-age z scores of infants with respect to the four patterns exhibited significant differences (P = 0.038, P = 0.030, P = 0.034, and P<0.001, respectively). The results demonstrated the effect of dietary FA patterns on FA compositions of serum and breast milk, and patterns mainly characterized by LC-PUFA may have potentially beneficial effects on maternal postpartum recovery and infant growth.

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother-Infant Pair: A Randomised Placebo-Controlled Trial in China.

BACKGROUND: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. METHODS: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. RESULTS: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. CONCLUSIONS: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.

Comparison of structural characteristics and bioactivities of polysaccharides from loquat leaves prepared by different drying techniques.

In the present study, freeze drying, hot-air drying, vacuum drying, and microwave drying at the microwave powers of 400, 600, and 800 W, respectively, were utilized to dry loquat leaves for evaluating the effects of different drying techniques on the physicochemical structures and bioactivities of polysaccharides extracted from loquat leaves (LLPs). Results demonstrated that the physicochemical structures and bioactivities of LLPs significantly affected by different drying techniques. The degrees of esterification, molar ratios of constituent monosaccharides, contents of uronic acids, apparent viscosities, and molecular weights of LLPs were varied by different drying techniques. Additionally, LLPs, particularly LLP-M4 which extracted from loquat leaves prepared by microwave drying at the power of 400 W, exerted remarkable in vitro binding capacities, strong inhibitory effects on α-amylase and α-glucosidase, and obvious antioxidant activities. Results indicated that the microwave drying could be an efficient drying technique before extraction of bioactive LLPs, and LLPs had great potential applications in the functional food and pharmaceutical industries.

Extraction Optimization, Structural Characterization, and Antioxidant Activities of Polysaccharides from Cassia Seed (Cassia obtusifolia).

In order to explore Cassia seed polysaccharides (CSPs) as natural antioxidants for application in the functional-food industry, microwave-assisted extraction (MAE) was optimized for the extraction of CSPs by using a response surface methodology. Furthermore, the chemical structures and antioxidant activities of CSPs extracted by MAE and hot water extraction were investigated and compared. The maximum extraction yield of CSPs extracted by MAE (8.02 ± 0.19%) was obtained at the optimized extraction parameters as follows: microwave power (415 W), extraction time (7.0 min), and ratio of water to raw material (51 mL/g). Additionally, the contents of the uronic acids, molecular weight, ratio of constituent monosaccharides, intrinsic viscosities, and degrees of esterification of CSPs were significantly affected by the MAE method. Moreover, CSPs exhibited remarkable 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) ABTS, 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl DPPH, nitric oxide, and hydroxyl radical scavenging activities as well as reducing power. The high antioxidant activities observed in CSPs extracted by MAE could be partially attributed to its low molecular weights and high content of unmethylated galacturonic acid. Results indicate that the MAE method could be an efficient technique for the extraction of CSPs with high antioxidant activity, and CSPs could be further explored as functional food ingredients.

Zinc supplementation reduces Candida infections in pediatric intensive care unit: a randomized placebo-controlled clinical trial.

Resistance to anti-fungal drugs has become the main cause for increasing incidence rate of Candida infections in pediatric intensive care units (PICU). Zinc supplementation has been shown to exhibit beneficial effects on many pediatric illnesses. This study aimed to investigate the efficacy of zinc supplementation on prevalence of candidemia and candiduria infections in PICU. 724 eligible children between 1 to 5 years old admitted in PICU were randomly assigned into either zinc supplementation group or placebo group. Primary endpoints were the number of Candida infections, length of PICU stay and cases of patient death 14 days after enrollment. Secondary endpoints were the incidence rates of candidemia and candiduria. The incidences of candiduria and candidemia were significantly lower in the zinc group than the placebo group. The length of PICU stay and cases of patient death were obviously lowered in the zinc group compared to the placebo group. In conclusion, zinc supplementation shows beneficial clinical efficacy in reducing Candida infections among PICU patients on broad-spectrum antibiotics with critical illnesses.

Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT.

Ferroptosis is a form of programmed cell death decided by iron-dependent lipid peroxidation, but its role in glioma cell death remains unclear. In this study, we found Pseudolaric acid B (PAB) inhibited the viabilities of glioma cells in vitro and in vivo, which was accompanied by abnormal increases of intracellular ferrous iron, H2O2 and lipid peroxidation, as well as depletion of GSH and cysteine. In vitro studies revealed that the lipid peroxidation and the cell death caused by PAB were both inhibited by iron chelator deferoxamine, but exacerbated by supplement of ferric ammonium citrate. Inhibition of lipid peroxidation with ferrostatin-1 or GSH rescued PAB-induced cell death. Morphologically, the cells treated with PAB presented intact membrane, shrunken mitochondria with increased membrane density, and normal-sized nucleus without chromatin condensation. Mechanistically, PAB improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2 and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT pathway, which further exacerbated accumulation of H2O2 and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment.

RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide.

RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine. Mitigation of intracellular H2O2 via supplement of GSH reversed shikonin-induced glycolysis suppression. The role of intracellular H2O2 in regulation of glycolysis suppression was further confirmed in the cells treated with exogenous H2O2. Notably, inhibition of RIP1 or RIP3 prevented intracellular H2O2 accumulation, which was correlated with preventing shikonin-induced downregulation of x-CT and depletion of GSH and cysteine. In addition, supplement of pyruvate effectively inhibited shikonin- or exogenous H2O2-induced accumulation of intracellular H2O2 and glioma cell death. Taken together, we demonstrated in this study that RIP1 and RIP3 contributed to shikonin-induced glycolysis suppression via increasing intracellular H2O2.

Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514, to suppress breast cancer progression and lung metastasis.

Metastasis is a major cause of breast cancer-associated mortality. Natural products extracted from herbs provide rich bioactive compounds with anticancer efficacy but may have limited or moderate potency and considerable toxicity. We developed a novel aziridonin, YD0514, by aziridinating oridonin, a natural product of the medicinal herb Rabdosia rubescens. In this study, we found that YD0514 significantly inhibited proliferation, motility, and adhesion of metastatic breast cancer cell lines MDA-MB-231, GI101, GILM2, and GILM3. YD0514 also decreased the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9), focal adhesion kinase (FAK), and integrin family members. Importantly, YD0514 suppressed the growth of metastatic breast cancer xenograft tumors and significantly inhibited lung metastasis in vivo. Lastly, we showed that YD0514's anti-metastatic effect on highly aggressive breast cancer is mediated via regulating the NRF-2/RHOA/ROCK signaling pathway. These results demonstrate that YD0514, the first active analog based on an oridonin D-ring modification, has the potential to be developed as an anti-metastasis therapy for patients with metastatic cancers.

Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and Antiinflammation to Neuroprotection.

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress has been made in structure activity relationship and mechanism of action studies of oridonin for the treatment of cancer and other diseases. This review provides a brief summary on oridonin and its analogs in cancer drug discovery and antiinflammation and highlights its emerging therapeutic potential in neuroprotection applications.

Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs.

The current agents used for renal cell carcinoma (RCC) only exhibit the moderate response rate among patients. Development of drug resistance eventually fuels the need of either more potent drugs or new drugs to target the resistant pathways. Oridonin is a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens and has been shown to have antitumor activities in many cancers. We previously developed new synthetic methodologies to modify structurally diversified diterpenoids and designed a series of nitrogen-enriched oridonin analogs. In this study, we screened a variety of oridonin analogs based on their cytotoxicity using MTT assay and identify the most potent candidate, namely, CYD-6-17. CYD-6-17 exhibited a high potency to inhibit the in vitro growth of several drug-resistant RCC cells as well as endothelial cells stimulated by tumor cells at nanomolar range. Delivery of CYD-6-17 significantly inhibited RCC tumor growth using xenograft model. Mechanistically, it targeted the 3-phosphoinositide-dependent protein kinase 1 gene that appeared to be a potent regulator of AKT and was associated with patient survival after targeted therapies. This offers a new rational therapeutic regimen of CYD-6-17 to drug-resistant RCC based on its novel mechanism of action.

Quercetin alleviates cell apoptosis and inflammation via the ER stress pathway in vascular endothelial cells cultured in high concentrations of glucosamine.

Glucosamine is a possible cause of vascular endothelial injury in the initial stages of atherosclerosis, through endoplasmic reticulum (ER) stress resulting in fatty streaks in the vascular wall. Quercetin is an anti­diabetic and cardiovascular protective agent that has previously been demonstrated to reduce ER stress in human umbilical vein endothelial cells (HUVECs). The present study aimed to investigate whether quercetin prevents glucosamine­induced apoptosis and inflammation via ER stress pathway in HUVECs. The effect of quercetin on cell viability, apoptosis, and protein expression levels of inflammatory cytokines and ER stress markers was investigated in glucosamine­supplemented HUVECs. Quercetin was demonstrated to protect against glucosamine­induced apoptosis, improved cell viability, and inhibited expression of pro­inflammatory factors and endothelin­1. Quercetin treatment also reduced the expression levels of glucose­regulated protein 78, phosphorylated protein kinase­like ER kinase, phosphorylated c­Jun N­terminal kinase and C/EBP homologous protein. In conclusion, quercetin may have auxiliary therapeutic potential against glucosamine­induced cell apoptosis and inflammation, which may be partially due to alleviation of ER stress.

Enhanced effects of novel oridonin analog CYD0682 for hepatic fibrosis.

BACKGROUND: Activated hepatic stellate cells (HSCs) are responsible for excess extracellular matrix (ECM) protein deposition in liver fibrosis. Previously, our group reported that the natural compound oridonin induces apoptosis, inhibits cell proliferation, and downregulates ECM proteins in activated HSC. In this study, the antifibrogenic effects of oridonin derivative CYD0682 on the activated human LX-2 and rat HSC-T6 stellate cell lines were investigated. METHODS: Cell proliferation was measured by alamarBlue assay. Apoptosis was detected by Cell Death ELISA and staining of Yo-Pro-1 and propidium iodide. Cell cycle was determined by flow cytometry. Immunoblot and immunofluorescence staining were performed for cellular protein expression. RESULTS: CYD0682 treatment significantly inhibited LX-2 cell proliferation in a dose- and time-dependent manner with an IC50 value of 0.49 µM for 48 h, ∼10-fold greater potency than oridonin. Similar results were observed in HSC-T6 cells. In contrast, 2.5 µM of CYD0682 treatment had no significant effects on proliferation of the human hepatocyte cell line C3A. CYD0682 treatment induced LX-2 cell apoptosis and S-phase cell cycle arrest and was associated with activation of p53, p21, and cleaved caspase-3. The myofibroblast marker protein α-smooth muscle actin and major ECM proteins type I collagen and fibronectin were markedly suppressed in a time- and dose-dependent fashion by CYD0682. Furthermore, pretreatment with CYD0682 blocked transforming growth factor-ß-induced type I collagen and fibronectin production. CONCLUSIONS: In comparison with oridonin, its novel derivative CYD0682 may act as a more potent antihepatic fibrosis agent.

Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation.

OBJECTIVE: Dihydrofolate reductase (DHFR) is a key protein involved in tetrahydrobiopterin (BH4) regeneration from 7,8-dihydrobiopterin (BH2). Dysfunctional DHFR may induce endothelial nitric oxide (NO) synthase (eNOS) uncoupling resulting in enzyme production of superoxide anions instead of NO. The mechanism by which DHFR is regulated is unknown. Here, we investigate whether eNOS-derived NO maintains DHFR stability. APPROACH AND RESULTS: DHFR activity, BH4 content, eNOS activity, and S-nitrosylation were assessed in human umbilical vein endothelial cells and in aortas isolated from wild-type and eNOS knockout mice. In human umbilical vein endothelial cells, depletion of intracellular NO by transfection with eNOS-specific siRNA or by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)-both of which had no effect on DHFR mRNA levels-markedly reduced DHFR protein levels in parallel with increased DHFR polyubiquitination. Supplementation of S-nitroso-l-glutathione (GSNO), a NO donor, or MG132, a potent inhibitor of the 26S proteasome, prevented eNOS silencing and PTIO-induced DHFR reduction in human umbilical vein endothelial cells. PTIO suppressed S-nitrosylation of DHFR, whereas GSNO promoted DHFR S-nitrosylation. Mutational analysis confirmed that cysteine 7 of DHFR was S-nitrosylated. Cysteine 7 S-nitrosylation stabilized DHFR from ubiquitination and degradation. Experiments performed in aortas confirmed that PTIO or eNOS deficiency reduces endothelial DHFR, which can be abolished by MG132 supplementation. CONCLUSIONS: We conclude that S-nitrosylation of DHFR at cysteine 7 by eNOS-derived NO is crucial for DHFR stability. We also conclude that NO-induced stabilization of DHFR prevents eNOS uncoupling via regeneration of BH4, an essential eNOS cofactor.

Grape seed proanthocyanidin extracts prevent high glucose-induced endothelia dysfunction via PKC and NF-κB inhibition.

In our study, it has been detected in vivo and in vitro that GSPE reversed high glucose-induced the increase of ICAM-1 and VCAM-1. It is shown that by western blotting detection, GSPE significantly inhibited the activation of NF-κB induced by high glucose while there was significant decrease of the expression of PKC with GSPE intervention. By adding the NF-κB blocker PDTC and the PKC inhibitor peptide 19-31(10(-6) M), no significant difference was found in the levels of VCAM-1 and ICAM-1 among GSPE group, the PKC inhibitor peptide 19-31-added GSPE group and the PDTC-added GSPE group. So the conclusion could be drawn that PKC inhibition must be involved in GSPE decreasing the level of ICAM-1 and VCAM-1.We proved for the first time that GSPE prevented high glucose-induced the increase of ICAM-1 and VCAM-1 by PKC and NF-κB inhibition. These findings show a novel mechanism of the action GSPE preventing endothelial dysfunction, which may have clinical application values.

Enhanced Performance of Community Health Service Centers during Medical Reforms in Pudong New District of Shanghai, China: A Longitudinal Survey.

BACKGROUND: The performance of community health service centers (CHSCs) has not been well monitored and analysed since China's latest community health reforms in 2009. The aim of the current investigation was to evaluate the performing trends of the CHSCs and to analyze the main factors that could affect the performance in Pudong new district of Shanghai, China. METHODS: A regional performance assessment indicator system was applied to the evaluation of Pudong CHSCs' performance from 2011 to 2013. All of the data were sorted out by a panel, and analyzed using descriptive statistics and a generalized estimating equation model. RESULTS: We found that the overall performance increased annually, with a growing number of CHSCs achieving high scores. Significant differences were observed in institutional management, public health services, basic medical services and comprehensive satisfaction during the period of three years. However, we found no differences in the service scores of Chinese traditional medicine (CTM). The investigation also demonstrated that the key factors affecting performance were the location, information system level, family GP program and medical association program rather than the size of the center. However, the medical association participation appeared to have a significant negative effect on performance. CONCLUSIONS: It can be concluded from the three-year investigation that the overall performance was improved, but that it could have been further enhanced, especially in institutional management and basic medical service; therefore, it is imperative that CHSCs undertake approaches such as optimizing the resource allocation and utilization, reinforcing the establishment of the information system level, extending the family GP program to more local communities, and promoting the medical association initiative.

Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats.

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.