DHA alleviated hepatic and adipose inflammation with increased adipocyte browning in high-fat diet-induced obese mice.

Obesity is associated with accumulation of inflammatory immune cells in white adipose tissue, whereas thermogenic browning adipose tissue is inhibited. Dietary fatty acids are important nutritional components and several clinical and experimental studies have reported beneficial effects of docosahexaenoic acid (DHA) on obesity-related metabolic changes. In this study, we investigated effects of DHA on hepatic and adipose inflammation and adipocyte browning in high-fat diet-induced obese C57BL/6J mice, and in vitro 3T3-L1 preadipocyte differentiation. Since visceral white adipose tissue has a close link with metabolic abnormality, epididymal adipose tissue represents current target for evaluation. A course of 8-week DHA supplementation improved common phenotypes of obesity, including improvement of insulin resistance, inhibition of macrophage M1 polarization, and preservation of macrophage M2 polarization in hepatic and adipose tissues. Moreover, dysregulated adipokines and impaired thermogenic and browning molecules, considered obesogenic mechanisms, were improved by DHA, along with parallel alleviation of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and mitochondrial DNA stress-directed innate immunity. During 3T3-L1 preadipocytes differentiation, DHA treatment decreased lipid droplet accumulation and increased the levels of thermogenic, browning, and mitochondrial biogenesis molecules. Our study provides experimental evidence that DHA mitigates obesity-associated inflammation and induces browning of adipose tissue in visceral epididymal adipose tissue. Since obesity is associated with metabolic abnormalities across tissues, our findings indicate that DHA may have potential as part of a dietary intervention to combat obesity.

Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD.

BACKGROUND: Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis. However, the role of emodin in DIC and its molecular targets remain unknown. HYPOTHESIS/PURPOSE: We aimed to clarify the protective role of emodin in mitigating DIC, as well as the mechanisms underlying this effect. METHODS: The model of DIC was established via the intraperitoneal administration of Dox at a dosage of 5 mg/kg per week for a span of 4 weeks. Emodin at two different doses (10 and 20 mg/kg) or a vehicle was intragastrically administered to the mice once per day throughout the Dox treatment period. Cardiac function, myocardial injury markers, pathological morphology of the heart, level of pyroptosis and mitochondrial function were assessed. Protein microarray, biolayer interferometry and pull-down assays were used to confirm the target of emodin. Moreover, GSDMD-overexpressing plasmids were transfected into GSDMD-/- mice and HL-1 cells to further verify whether emodin suppressed GSDMD activation. RESULTS: Emodin therapy markedly enhanced cardiac function and reduced cardiomyocyte pyroptosis in mice induced by Dox. Mechanistically, emodin binds to GSDMD and inhibits the activation of GSDMD by targeting the Trp415 and Leu290 residues. Moreover, emodin was able to mitigate Dox-induced cardiac dysfunction and myocardial injury in GSDMD-/- mice overexpressing GSDMD, as shown by increased EF and FS, decreased serum levels of CK-MB, LDH and IL-1ß and mitigated cell death and cell morphological disorder. Additionally, emodin treatment significantly reduced GSDMD-N expression and plasma membrane disruption in HL-1 cells overexpressing GSDMD induced by Dox. In addition, emodin reduced mitochondrial damage by alleviating Dox-induced GSDMD perforation in the mitochondrial membrane. CONCLUSION: Emodin has the potential to attenuate DIC by directly binding to GSDMD to inhibit pyroptosis. Emodin may become a promising drug for prevention and treatment of DIC.

Tetramethylpyrazine alleviates mitochondrial abnormality in models of cerebral ischemia and oxygen/glucose deprivation Reoxygenation.

Traditional herbal medicine Ligusticum wallichii Franchat (Chuan Xiong) is frequently prescribed and highly recommended to patients with stroke. Rodent studies have demonstrated the neuroprotective effects of its active component tetramethylpyrazine against post-stroke brain injury and highlighted its role in antioxidant, anti-inflammation, and anti-apoptosis activity. Using permanent cerebral ischemia in rats and oxygen/glucose deprivation and reoxygenation (OGDR) in rat primary neuron/glia cultures, this study sheds light on the role of mitochondria as crucial targets for tetramethylpyrazine neuroprotection. Tetramethylpyrazine protected against injury and alleviated oxidative stress, interleukin-1ß release, and caspase 3 activation both in vivo and in vitro. Reduction of mitochondrial biogenesis- and integrity-related proliferator-activated receptor-gamma coactivator-1 alpha, mitochondrial transcription factor A (TFAM), translocase of outer mitochondrial membrane 20, mitochondrial DNA, and citrate synthase activity, as well as activation of mitochondrial dynamics disruption-related Lon protease, dynamin-related protein 1 (Drp1) phosphorylation, stimulator of interferon genes, TANK-binding kinase 1 phosphorylation, protein kinase RNA-like endoplasmic reticulum kinase phosphorylation, eukaryotic initiation factor 2α phosphorylation, and activating transcription factor 4 were revealed in permanent cerebral ischemia in rats and OGDR in neuron/glia cultures. TMP alleviated those biochemical changes. Our findings suggest that preservation or restoration of mitochondrial dynamics and functional integrity and alleviation of mitochondria-oriented pro-oxidant, pro-inflammatory, and pro-apoptotic cascades are alternative neuroprotective mechanisms of tetramethylpyrazine. Additionally, mitochondrial TFAM and Drp1 as well as endoplasmic reticulum stress could be targeted by TMP to induce neuroprotection. Data of this study provide experimental base to support clinical utility and value of Chuan Xiong towards stroke treatment and highlight an alternative neuroprotective target of tetramethylpyrazine.

Effects of the coupling water and fertilizer on soil phosphorus components in alfalfa field in Eastern Inner Mongolia, China.

Soil phosphorus (P) could be categorized into organic and inorganic forms, with diffe-rent capabilities of nutrient supply. Exploring soil P components through liquid 31P-NMR would provide an important theoretical basis for soil P nutrition regulation. This study addressed the characteristic of P in alfalfa (Medicago sativa) soil via the pot experiment. There were two scenarios of treatments with conventional and dry water combined with different P fertilizer levels (P0-P4: 0, 0.025, 0.05, 0.1, and 0.2 g P2O5·kg-1soil). The characteristics of P components in alfalfa soil under water-fertilizer coupling conditions were measured by liquid 31P-NMR. Results showed that under different water and fertilizer treatments, soil inorganic P was mainly composed of inorganic orthophosphate, pyrophosphate and inorganic polyphosphate. Inorganic orthophosphate was the dominant component of inorganic P, which could be reduced by drought. High P application (P4) could increase the contents of soil inorganic polyphosphates and inorganic pyrophosphates. Among the organic P components, monoester orthophosphate was dominant, the conversion and utilization of which in alfalfa soil were affected by drought. Overall, the rational management of water and fertilizer could effectively regulate the conversion and utilization of P nutrients in alfalfa soil in Eastern Inner Mongolia.

Magnesium lithospermate B supplementation improved prenatal Bisphenol A exposure-induced metabolic abnormalities in male offspring.

Obesity is closely linked with metabolic diseases, while life and prenatal exposure to endocrine-disrupting chemicals has been implicated in the development of obesity. Magnesium lithospermate B (MLB), an active compound of Salvia miltiorrhiza (Danshen), has beneficial effects on insulin resistance and metabolic abnormalities in diet-induced obese rodents. Since exposure to endocrine-disrupting chemical Bisphenol A (BPA) during pregnancy mimics the effects of high fat diet-induced alterations of glucose and lipid metabolism in adult male offspring, the effects of daily MLB supplementation for 4 weeks on metabolic abnormalities in rats weaning from prenatal BPA-exposed dams were investigated. BPA-exposed rats developed obesity and adiposity concurrent with hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and elevation of circulating glucagon and free fatty acids. Increased hepatic fatty acid synthesis and decreased fatty acid ß-oxidation, activation of adipocytic adipogenesis, maturation, and lipogenesis, as well as reduction of muscular glucose uptake were demonstrated in BPA-exposed rats. The aforementioned alterations were improved by MLB supplementation. Additionally, MLB displayed negative effects on glucocorticoid receptor action and inflammation, and promoted lipolysis and thermogenesis in the adipose tissues. In conclusion, our findings suggest that MLB may be a potential therapeutic compound against metabolic diseases, including maternal exposure-induced metabolic abnormalities.

Identification and characterization of potential antioxidant components in Isodon amethystoides (Benth.) Hara tea leaves by UPLC-LTQ-Orbitrap-MS.

Isodon amethystoides (Benth.) Hara (IA) tea is a commonly used dietetic Chinese herb and employed for the treatments of tumor and lung abscess. To assess chemical composition and antioxidant capacity of IA leaves extract, a UPLC-LTQ-Orbitrap-MS method and antioxidant tests were used, respectively. 17 compounds were identified including Vinyl caffeate (1), 3,4-dimethoxyphenyl-ß-D-glucopyranoside (2), Rutin (3), Quercetin (4), Loliolide (5), Caffeic acid (6), Rubesanolide D (7), Isorhamnetin (8), Lambertic acid (9), 6, 7-Dehydroroyleanone (10), Dihydrorabdokunmin C (11), Nervosin (12), Quercitrin (13), Vitexin (14), ß-sitosterol (15), Wangzaozin A (16), Amethystonoic acid (17). Among these, 1-14 compounds were novel and have not been reported ever before in IA while component 10 was a novel finding within this genus. Flavonoid components showed better free radical scavenging ability and profound correlation was observed between diterpenoid compounds content and flavonoids activity. Our results provide experimental basis for extraction and separation of chemical constituents of IA which are antioxidant in nature.

New-onset intrinsic and paced QRS morphology of right bundle branch block pattern after atrioventricular nodal ablation: Longitudinal dissociation or anatomical bifurcation?

We performed left bundle pacing combined with atrioventricular nodal (AVN) ablation in a patient with persistent atrial fibrillation and refractory symptomatic heart failure. The major findings were new-onset intrinsic and paced QRS morphology of right bundle branch block (RBBB) pattern after AVN ablation which was performed at a more atrial site compared with the pacing site and the paced RBBB pattern could not be corrected regardless of the pacing output. Longitudinal dissociation cannot explain this observation, while anatomical separation could. We also confirm this was proximal left bundle pacing rather than His bundle pacing.

The characteristics of the electrocardiogram and the intracardiac electrogram in left bundle branch pacing.

INTRODUCTION: Left bundle branch pacing (LBBP) has recently been reported to maintain left ventricular electrical synchrony with a low and stable threshold. However, the electrocardiogram (ECG) definitions of LBBP have not been well established. We report four cases to show the characteristics of the ECG and the intracardiac electrogram (EGM) in LBBP. METHODS AND RESULTS: Four patients, two with an atrioventricular block (AVB) and two with left bundle branch block (LBBB), were included in the study. LBBP was performed and the ECGs and EGMs were collected and compared at different pacing outputs. Selective LBBP (S-LBBP) was defined as only capturing the LBB with a typical RBBB morphology and a discrete component between the pacing stimulus and ventricular activation in the EGMs. While nonselective LBBP (NS-LBBP) captured both the LBB and the local myocardium, resulting in a narrow right bundle branch block (RBBB) morphology without the discrete component. The left bundle branch (LBB) potential was recorded in two cases during narrow QRS complex or LBBB correction by selective His bundle pacing and SLBBP (n = 3) was achieved. A constant and shortest stimulus to left ventricular activation time (LVAT) in LBBP was obtained at different pacing outputs. CONCLUSION: The ECG and EGM characteristics of LBBP can be summarized as: 1) RBBB pattern; 2) usually with the LBB potential; 3) SLBBP with specific ECG changes and a discrete component in EGM; and 4) with a constant and shortest stimulus to LVAT at different pacing outputs. Further studies are necessary to confirm these observations.

Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats.

Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-ß1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3. BDL rats showed increased hepatic NF-κB/AP-1 activities, inflammatory cell infiltration/accumulation, and cytokine production, and these signs of hepatic inflammation were ameliorated by rosmarinic acid. Mechanistic study revealed an inhibitory effect of rosmarinic acid on the axis of the high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) in BDL rats. Results of cultured hepatic stellate cells further showed the impacts of rosmarinic acid which attenuated TGF-ß1-induced stellate cell mitogenic and fibrogenic activation. Our findings support the concept that rosmarinic acid could serve as a hepatoprotective agent, and dietary rosmarinic acid supplementation may be beneficial in terms of improving cholestasis-related liver injury via mechanisms involving resolution of oxidative burden and down-regulation of HMGB1/TLR4, NF-κB, AP-1, and TGF-ß1/Smad signaling.

Nitric oxide induces monosaccharide accumulation through enzyme S-nitrosylation.

Nitric oxide (NO) is extensively involved in various growth processes and stress responses in plants; however, the regulatory mechanism of NO-modulated cellular sugar metabolism is still largely unknown. Here, we report that NO significantly inhibited monosaccharide catabolism by modulating sugar metabolic enzymes through S-nitrosylation (mainly by oxidizing dihydrolipoamide, a cofactor of pyruvate dehydrogenase). These S-nitrosylation modifications led to a decrease in cellular glycolysis enzymes and ATP synthase activities as well as declines in the content of acetyl coenzyme A, ATP, ADP-glucose and UDP-glucose, which eventually caused polysaccharide-biosynthesis inhibition and monosaccharide accumulation. Plant developmental defects that were caused by high levels of NO included delayed flowering time, retarded root growth and reduced starch granule formation. These phenotypic defects could be mediated by sucrose supplementation, suggesting an essential role of NO-sugar cross-talks in plant growth and development. Our findings suggest that molecular manipulations could be used to improve fruit and vegetable sweetness.

Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND METHODS: Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches. RESULTS: Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-ß1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways. CONCLUSIONS: The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down-regulation of NF-κB, AP-1, and TGF-ß/Smad signaling, probably via interference with the HMGB1/TLR4 axis.

Population Pharmacokinetics and Pharmacodynamics of Piperacillin/Tazobactam in Patients with Nosocomial Infections.

OBJECTIVE: The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections. METHODS: In total, 310 PIP and 280 TAZ concentration-time points were collected at steady state over multiple dosing intervals from 50 patients who received PIP/TAZ infused within 30 min or over 3 h. Drug analysis was performed by high-performance liquid chromatography (HPLC). Nonlinear mixed effects modeling was employed to develop PPK model and 1000 Monte Carlo simulation was used to predict the probability of target attainment (PTA) with a target time of non-protein-bound concentration above MIC > 50 % of the dosing interval. RESULTS: A model with one-compartment model had the best predictive performance for the PPK model. The population estimates of PIP were 13.8 L/h (31.1 %) for clearance (CL) and 21.7 L (38 %) for volume of distribution (V). The population estimates of TAZ were 9.3 L/h (29.1 %) for CL and 16 L (35.3 %) for V. Influence of creatinine clearance (CLcr) and body weight were identified as important covariates for PIP/TAZ CL and V, respectively. A 30-min infusion of 4 g every 6 h achieved robust (≥90 %) PTAs for MIC ≤ 16 mg/L. As an alternative mode of administration, a 3-h infusion of 4 g every 6 h achieved robust PTAs for Pseudomonas aeruginosa and Klebsiella pneumoniae. CONCLUSIONS: Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 16 and 40 mg/L.

Advances in the pharmacological activities and mechanisms of diosgenin.

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

Cisplatin-based chronotherapy for advanced non-small cell lung cancer patients: a randomized controlled study and its pharmacokinetics analysis.

PURPOSE: We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin. METHODS: Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method. RESULTS: There is no significant difference in total response rate between chronotherapy group (52.94%) and routine chemotherapy group (50.00%), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy (37.50%), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy group (33.33%), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05). CONCLUSIONS: Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.

Advances in the pharmacological activities and mechanisms of diosgenin / 中国天然药物

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats.

Cellular inflammatory response plays an important role in ischemic brain injury and anti-inflammatory treatments in stroke are beneficial. Dietary supplementation with docosahexaenoic acid (DHA) shows anti-inflammatory and neuroprotective effects against ischemic stroke. However, its effectiveness and its precise modes of neuroprotective action remain incompletely understood. This study provides evidence of an alternative target for DHA and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of 3 consecutive days of DHA preadministration on circulating and intracerebral cellular inflammatory responses in a rat model of permanent cerebral ischemia. DHA exhibited a neuroprotective effect against ischemic deficits by reduction of behavioral disturbance, brain infarction, edema and blood-brain barrier disruption. The results of enzymatic assay, Western blot, real-time reverse transcriptase polymerase chain reaction and flow cytometric analysis revealed that DHA reduced central macrophages/microglia activation, leukocyte infiltration and pro-inflammatory cytokine expression and peripheral leukocyte activation after cerebral ischemia. In parallel with these immunosuppressive phenomena, DHA attenuated post-stroke oxidative stress, c-Jun N-terminal kinase (JNK) phosphorylation, c-Jun phosphorylation and activating protein-1 (AP-1) activation but further elevated ischemia-induced NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. DHA treatment also had an immunosuppressive effect in lipopolysaccharide/interferon-γ-stimulated glial cultures by attenuating JNK phosphorylation, c-Jun phosphorylation and AP-1 activation and augmenting Nrf2 and HO-1 expression. In summary, we have shown that DHA exhibited neuroprotective and anti-inflammatory effects against ischemic brain injury and these effects were accompanied by decreased oxidative stress and JNK/AP-1 signaling as well as enhanced Nrf2/HO-1 expression.

[A case-control study regarding tea consumption and risk of hip fractures in middle-aged and elderly Chinese].

OBJECTIVE: To assess the impact of tea consumption on the risk of osteoporotic hip fractures. METHODS: Between January 2008 and June 2012, 581 (148 males, 433 females) incident cases of hip fractures were enrolled from four hospitals in Guangdong province, with 581 sex- and age-matched (± 3 years) controls from either hospitals or communities. Face-to-face interviews were conducted to collect data pertaining to tea drinking and various covariates. RESULTS RESULTS: from univariate conditional logistic analyses showed that an inverse association was observed in tea drinking and hip fracture risk. Longer time, greater frequency and dosage of tea consumption were dose-dependently associated with lower risk of hip fractures (P-trend < 0.05). Compared to non-drinkers, the odd ratios related to regular tea drinkers, subgroups with different length, frequency, dosage, type of tea consumption were ranged between 0.54 and 0.74 (all P < 0.05). After adjustment for factors as age, daily energy intake, BMI, education levels, passive smoking, calcium supplement and physical activity, the dose-dependent associations among above said factors still remained significant. However, the strength of the association lowered slightly. The beneficial effect of tea was significant only in men but not in women. Similar effects were found in subjects with different education levels. CONCLUSION: Regular tea drinking habit might decrease the risk of osteoporotic hip fractures in the elderly males.

A case-control study regarding tea consumption and risk of hip fractures in middle-aged and elderly Chinese / 中华流行病学杂志

Objective To assess the impact of tea consumption on the risk of osteoporotic hip fractures.Methods Between January 2008 and June 2012,581 (148 males,433 females) incident cases of hip fractures were enrolled from four hospitals in Guangdong province,with 581 sex-and age-matched (± 3 years) controls from either hospitals or communities.Face-to-face interviews wer conducted to collect data pertaining to tea drinking and various covariates.Results Results from univariate conditional logistic analyses showed that an inverse association was observed in tea drinking and hip fracture risk.Longer time,greater frequency and dosage of tea consumption were dose-dependently associated with lower risk of hip fractures (P-trend ＜0.05).Compared to non drinkers,the odd ratios related to regular tea drinkers,subgroups with different length,frequency,dosage,type of tea consumption were ranged between 0.54 and 0.74 (all P＜0.05).After adjustment for factors as age,daily energy intake,BMI,education levels,passive smoking,calcium supplement and physical activity,the dose-dependent associations among above said factors still remained significant.However,the strength of the association lowered slightly.The beneficial effect of tea was significant only in men but not in women.Similar effects were found in subjects with different education levels.Conclusion Regular tea drinking habit might decrease the risk of osteoporotic hip fractures in the elderly males.

Beneficial effect of docosahexaenoic acid on cholestatic liver injury in rats.

Bile duct obstruction and subsequent cholestasis are associated with hepatocellular injury, cholangiocyte proliferation, stellate cell activation, Kupffer cell activation, oxidative stress, inflammation and fibrosis. Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid that has been shown to possess health beneficial effects, including hepatoprotection. However, the molecular mechanism of DHA-mediated hepatoprotection is not fully understood. In the present study, we report the protective effect of DHA on cholestatic liver injury. Cholestasis was produced by bile duct ligation (BDL) in male Sprague-Dawley rats for 3 weeks. Daily administration of DHA was started 2 weeks before injury and lasted for 5 weeks. In comparison with the control group, the BDL group showed hepatic damage as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, inflammation and oxidative stress. These pathophysiological changes were attenuated by chronic DHA supplementation. DHA alleviated BDL-induced transforming growth factor beta-1 (TGF-ß1), intereukin-1beta, connective tissue growth factor and collagen expression. The anti-fibrotic effect of DHA was accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad 2/3 activity critical to the fibrogenic potential of TGF-ß1. DHA also attenuated BDL-induced leukocyte accumulation and nuclear factor-κB (NF-κB) activation. Further studies demonstrated an inhibitory effect of DHA on redox-sensitive intracellular signaling molecule extracellular signal-regulated kinase (ERK). Taken together, the hepatoprotective, anti-inflammatory and anti-fibrotic effects of DHA seem to be multifactorial. The beneficial effects of chronic DHA supplementation are associated with anti-oxidative and anti-inflammatory potential as well as down-regulation of NF-κB and transforming growth factor beta/Smad signaling probably via interference with ERK activation.