Docosahexaenoic Acid-Enriched Phosphatidylcholine Exerted Superior Effects to Triglyceride in Ameliorating Obesity-Induced Osteoporosis through Up-Regulating the Wnt/ß-Catenin Pathway.

A growing number of studies reported that obesity is one of the major inducements for osteoporosis by promoting excessive adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Marine-derived DHA-enriched phosphatidylcholine (DHA-PC) exhibited activities to improve ovariectomized-induced osteoporosis and kidney damage. However, the potential effect of DHA-PC and efficacy differences between DHA-PC and traditional DHA (DHA-triglyceride, DHA-TG) on BMSCs differentiation in obesity-induced osteoporosis were not clear. In the present study, obesity-induced osteoporotic mice were supplemented with DHA-TG and DHA-PC for 120 days. Results showed that supplementing with DHA-PC improved the bone mineral density and biomechanical properties, increased the new bone formation rate by 55.2%, and reduced the amount of bone marrow fat to a greater extent than DHA-TG. Further in vitro results showed that DHA-PC significantly promoted the osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs. Mechanistically, DHA-PC supplement up-regulated Wnt/ß-catenin pathway in BMSCs and up-regulated the expression of osteogenic transcription factors, thereby promoting osteogenic differentiation. In summary, DHA-PC exerted a superior effect to DHA-TG in improving obesity-induced osteoporosis. The results provided new evidence for the application of different molecular forms of DHA in treatment of osteoporosis.

Urinary non-targeted toxicokinetics and metabolic fingerprinting of exposure to 3-monochloropropane-1,2-diol and glycidol from refined edible oils.

The widespread presence of 3-monochloropropane-1,2-diol (3-MCPD) and glycidol in refined edible oils have raised food industrial and public health concerns, but their specific biomarkers of exposure and urinary metabolic pathways indicating nephrotoxicity remain largely unknown. Here, we unraveled the in vivo biotransformation of these two contaminants and revealed how they affect metabolic pathways in rats. Urine metabolomes in rats administered with glycidol or 3-MCPD were investigated using ultra-high performance liquid chromatography combined with a quadrupole-orbitrap high-resolution mass spectrometry. Compared to the currently acknowledged metabolite which is only 2,3-dihydroxypropyl mercapturic acid, we identified 8 and 4 new specific exposure biomarkers of glycidol and 3-MCPD, respectively, via mapping the glyceryl polymerization and glutathione and sulfur conjugation. The changes of metabolites in the surrounding metabolic network were investigated to further gain insight into their metabolic fates. Exposure to glycidol up-regulated citrate, isocitrate, ketoglutarate, malate, and pyruvate in the tricarboxylic acid cycle and glycolysis pathways, while 3-MCPD intake down-regulated these signal molecules in both pathways. Nonetheless, L-cysteine, proline, and arginine were significantly decreased by the effect of either glycidol or 3-MCPD. Our findings first map the urinary metabolomics of both contaminants from edible oils and advance the omics-level recognition for their observational health hazards.

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS: Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved ß cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS: DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.

Cooking oil/fat consumption and deaths from cardiometabolic diseases and other causes: prospective analysis of 521,120 individuals.

BACKGROUND: Increasing evidence highlights healthy dietary patterns and links daily cooking oil intake with chronic diseases including cardiovascular disease (CVD) and diabetes. However, food-based evidence supporting the consumption of cooking oils in relation to total and cardiometabolic mortality remains largely absent. We aim to prospectively evaluate the relations of cooking oils with death from cardiometabolic (CVD and diabetes) and other causes. METHODS: We identified and prospectively followed 521,120 participants aged 50-71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Individual cooking oil/fat consumption was assessed by a validated food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for mortality through the end of 2011. RESULTS: Overall, 129,328 deaths were documented during a median follow-up of 16 years. Intakes of butter and margarine were associated with higher total mortality while intakes of canola oil and olive oil were related to lower total mortality. After multivariate adjustment for major risk factors, the HRs of cardiometabolic mortality for each 1-tablespoon/day increment were 1.08 (95% CI 1.05-1.10) for butter, 1.06 (1.05-1.08) for margarine, 0.99 (0.95-1.03) for corn oil, 0.98 (0.94-1.02) for canola oil, and 0.96 (0.92-0.99) for olive oil. Besides, butter consumption was positively associated with cancer mortality. Substituting corn oil, canola oil, or olive oil for equal amounts of butter and margarine was related to lower all-cause mortality and mortality from certain causes, including CVD, diabetes, cancer, respiratory disease, and Alzheimer's disease. CONCLUSIONS: Consumption of butter and margarine was associated with higher total and cardiometabolic mortality. Replacing butter and margarine with canola oil, corn oil, or olive oil was related to lower total and cardiometabolic mortality. Our findings support shifting the intake from solid fats to non-hydrogenated vegetable oils for cardiometabolic health and longevity.

Current intake levels of potatoes and all-cause mortality in China: A population-based nationwide study.

OBJECTIVE: Current levels of potato consumption in relation to mortality in Chinese people remains unknown. The aim of this study was to investigate the intakes of total potatoes, fried potatoes, non-fried potatoes, and sweet potatoes as dietary carbohydrate sources in relation to all-cause mortality in the China Health and Nutrition Survey (CHNS). METHODS: Overall 14 117 participants ≥20 y of age were included, with a median follow-up of 14 y. The cumulative average consumption of potatoes and other foods were calculated and validated using weighing methods in combination with 3-d, 24-h dietary recalls at both household and individual levels. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models after multivariate adjustment. RESULTS: We documented 1007 deaths among the participants. The low and moderate intakes of total potatoes, fried potatoes, and non-fried potatoes were inversely associated with mortality. Compared with non-consumers, the intakes of total potatoes (HR, 0.48; 95% CI, 0.38-0.59), fried potatoes (HR, 0.44; 95% CI, 0.34-0.56), and non-fried potatoes (HR, 0.47; 95% CI, 0.37-0.61) at low consumption levels were most significantly related to lower mortality. Sweet potato consumption was inversely associated with mortality after full adjustment (HR, 0.82; 95% CI, 0.69-0.96) compared with non-consumers. Substituting grains and mixed beans for potatoes with equal amounts at high consumption levels strengthened the inverse associations. CONCLUSION: In the CHNS, current low and moderate, but not high levels of total potato and fried/non-fried potato consumption as well as sweet potato consumption were inversely associated with all-cause mortality among Chinese people.

Quercetin protects retina external barrier from oxidative stress injury by promoting autophagy.

Purpose: This study aimed to investigate the protective effects of quercetin on the tight junction proteins of human retinal pigment epithelial cells (ARPE-19 cells) suffering from oxidative stress injury and explore the possible mechanism.Methods: H2O2 (300 µM) was used to establish an oxidative stress model of ARPE-19 cells. ARPE-19 cells were pretreated with different concentrations (0-80 µM) of quercetin before H2O2 exposure. The expression and distribution of tight junction proteins and autophagy-related proteins were detected by Western blot and immunostaining. ARPE-19 cells were pretreated with 5 mM 3-methyladenine (3-MA).Results: The cell viability weakened in the H2O2 group compared with the control group. However, it was preserved after pretreatment with quercetin. It was observed that the expression levels of occludin, claudin-1 were decreased in the H2O2 group. Quercetin treatment significantly enhanced the expression levels of them as compared to the H2O2 group. H2O2 alone strongly decreased the Zonula occludens protein 1 (ZO-1) expression in the cytomembrane. Quercetin supplementation enhanced the accumulation of ZO-1 in ARPE-19 cells. The expression levels of Beclin-1 and Microtubule associated protein light chain 3 II (LC-3II) increased, and that of P62 decreased in the quercetin protection group. The appearance of LC-3II, which examined by immunofluorescence experiments, enhanced in the quercetin protection group as compared with the control group. The expression levels of beclin-1 and LC-3II increased, and that of P62 increased in the autophagy-inhibited group compared with the quercetin protection group. The levels of occludin and claudin-1 also decreased.Conclusion: Quercetin prevents the loss of tight junction proteins by upregulating autophagy after oxidative stress in ARPE-19 cells.

Cooking Oil Consumption Is Positively Associated with Risk of Type 2 Diabetes in a Chinese Nationwide Cohort Study.

BACKGROUND: Evidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown. OBJECTIVES: We aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort. METHODS: Overall 15,022 Chinese adults aged ≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D. RESULTS: A total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D. CONCLUSIONS: Intakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.

Plant-sourced cooking oil consumption is associated with lower total mortality in a longitudinal nationwide cohort study.

BACKGROUND & AIMS: Evidence linking individual cooking oil consumption with total mortality is limited in China. The aim of this study was to examine the associations of intakes of plant-sourced and animal-sourced cooking oils with total mortality in a Chinese nationwide cohort. METHODS: We analyzed data from 14,305 adults aged ≥20 y at entry in the China Health and Nutrition Survey (CHNS). The 3-day 24-h dietary records were used to collect dietary information. Cox proportional hazards regression models were established to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death. RESULTS: Overall 1006 deaths were documented during a median of 14 years (199,091 person-years) of follow-up. Multivariate-adjusted HRs (95% CIs) of total mortality via comparing the highest tertile of cooking oil consumption with no consumption were 0.86 (0.70-1.06) for lard, 0.59 (0.47-0.74) for peanut oil, 0.71 (0.54-0.93) for soybean oil, 0.76 (0.61-0.94) for canola oil, 0.71 (0.50-0.99) for salad oil, and 0.59 (0.44-0.79) for other plant cooking oils. Replacing animal cooking oils with 1 tablespoon/d of total plant cooking oils or other plant cooking oils was related to 4% or 17% lower total mortality, respectively, while consumption of peanut oil or salad oil in replacement of animal cooking oils had a marginal inverse association with total mortality. CONCLUSIONS: Intakes of plant-sourced cooking oils, including peanut oil, soybean oil, canola oil, salad oil, and other plant cooking oils and substituting plant cooking oils for animal cooking oils were associated with lower total mortality among general Chinese population (NCT03259321).

[Professor JIN Ya-pei's experience in the treatment of perimenopausal insomnia with navel acupuncture combined with body acupuncture].

Professor JIN Ya-pei 's thinking on the diagnosis and treatment of perimenopausal insomnia and the characteristics of acupuncture and moxibustion were summarized. Professor JIN Ya-pei believes that the pathogenesis of perimenopausal insomnia is imbalance of yin and yang, and disharmony of the heart and the kidney. Additionally, it is also closely related to liver stagnation and spleen deficiency. The syndrome differentiation and treatment principle of traditional Chinese medicine is combined with the theory of I Ching. Navel acupuncture is adopted at the points around the umbilicus to achieve the tonification for the deficiency condition and the reducing for the excess one. Additionally, the body acupuncture is used to regulate menstruation. The coordination of these two acupuncture regimens achieves the significant effect on perimenopausal insomnia, which provides a new reference and approach to the clinical treatment of perimenopausal insomnia.

Current level of fish and omega-3 fatty acid intakes and risk of Type 2 diabetes in China.

Whether fish and marine omega-3 polyunsaturated fatty acid (PUFA) intakes are linked to type 2 diabetes (T2D) risk remains unclear in China. We aimed to assess the long-term associations in a nationwide cohort. Overall 15,100 Chinese adults, aged ≥20 years, were included from China Health and Nutrition Survey. The cumulative averages of fish and marine omega-3 PUFA intakes were evaluated based on 3-day 24-h records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of T2D risk. Overall 1017 T2D cases were documented over a median of 14 years of follow-up. Compared with non-fish consumers, low and moderate fish consumption were associated with higher T2D risk whereas high fish consumption was not associated. Multivariable-adjusted HRs (95% CIs) for low and moderate fish consumption were 1.43 (1.09, 1.86) and 1.42 (1.07, 1.85) respectively in men, and were 1.58 (1.22, 2.02) and 1.39 (1.08, 1.83) respectively in women. In meat substitution analyses, low and moderate fish consumption was related to 55% and 69% higher T2D risk for men, and was associated with 68% and 54% higher T2D risk for women, respectively. Fried but not non-fried fish intake was associated with higher T2D risk. Intake of marine omega-3 PUFAs was dose-dependently associated with higher T2D risk for both men and women (P-trend<0.001). Overall low and moderate intakes of fish, especially fried fish, and marine omega-3 PUFAs were associated with higher T2D risk. Current level of fish and marine omega-3 PUFA consumption is not protective against T2D incidence among Chinese people.

Differential Anti-Adipogenic Effects of Eicosapentaenoic and Docosahexaenoic Acids in Obesity.

SCOPE: To assess the associations of plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with body fat in a population-based sample and explore the mechanism of action based on browning of white adipose tissue (WAT) in high-fat-diet-induced obese (DIO) mice and 3T3-L1 adipocytes. METHODS AND RESULTS: Plasma EPA and DHA of 1719 adults in the National Health and Nutrition Examination Survey (2003-2004) are determined by gas chromatography mass spectrometry, while total body fat is measured by dual-energy X-ray absorptiometry. DIO mice are fed a high-fat diet supplemented with EPA or DHA (1% wt/wt) for 15 weeks and 3T3-L1 preadipocytes are treated with EPA or DHA during differentiation. Plasma DHA but not EPA is associated with lower body fat mass (ptrend < 0.0001), which persists in overweight/obese subjects (ptrend = 0.02). DHA supplementation reduces inguinal WAT and exhibits a more pronounced thermogenic effect than EPA in DIO mice. In vitro, the browning process is induced after 2-day and 6-day treatment with DHA and EPA, respectively. CONCLUSION: Plasma DHA but not EPA is inversely associated with body fat mass. The more potent anti-adipogenic effect of DHA than EPA may involve a better capability of inducing browning of WAT for DHA.

[Effects of Cyanobacterial Blooms in Eutrophic Lakes on Water Quality of Connected Rivers].

The location at which the Liangxi River meets Meiliang Bay of Lake Taihu was selected to explore the influence and controlling factors of algal blooms on the connected rivers. The cyanobacterial particulates and water quality parameters including nitrogen, phosphorus, and dissolved oxygen were monitored daily during the summer bloom season. The spatial variation in water quality parameters along the river were also surveyed, and data from hydrological and meteorological factors such as discharge, temperature, and wind field characteristics over the same period were collected to help investigate the effects of cyanobacterial blooms on the water quality of connected rivers. The results showed that the total fresh biomass of algal blooms entering Liangxi River for three months during the summer cyanobacterial bloom period in Meiliang Bay was 9733 t, which was similar to the amount harvested from the entire lake throughout the year. The flux of water bloom particles to the river varied widely, ranging from 75-496 t·d-1, with an average of 105 t·d-1. The flux was primarily controlled by hydrological and meteorological conditions. Water volume, temperature, and wind direction were the most important influencing factors. Lake water with a large amount of cyanobacterial particles entering the river can significantly improve the dissolved oxygen, ammonia-nitrogen, and other qualities of the river water in the city. It also significantly increased the concentrations of nutrients such as particulate nitrogen and phosphorus in the river, while it had a relatively weak effect on dissolved nitrogen and phosphorus. Spatially, the chlorophyll a concentration rapidly decreased with increasing distance from the lake, and the concentration of nitrogen and phosphorus exist as particulate cyanobacteria also declined. Upon being discharged into the canal 7 km away, the cyanobacterial particles were largely decomposed, and chlorophyll a content from the phytoplankton collected from the river by a 67 µm net decreased from 152.93 µg·L-1 to 1.99 µg·L-1. The results indicated that lakes plagued with cyanobacterial blooms have a great impact on the water quality of surrounding rivers. Although the connection between rivers and lakes can effectively relieve black spots and solve the black and odorous phenomenon in urban rivers, it had a great impact on nutrients concentration in the rivers. Depending on the different protection targets of rivers and lakes, lake water blooms and hydro-meteorological factors should be considered during water transfer management to optimize the water ecological services of lakes and rivers.

Dietary Fats in Relation to Total and Cause-Specific Mortality in a Prospective Cohort of 521 120 Individuals With 16 Years of Follow-Up.

RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.

[Effects of Hydrological and Meteorological Conditions on Diatom Proliferation in Reservoirs].

The proliferation of diatoms is an ecological disaster that harms the water quality of many reservoirs in China. In order to reveal the driving factors of abnormal algal blooms in reservoirs, phytoplankton community structure and the associated environmental factors from 2009 to 2016 from Shahe Reservoir in Tianmuhu were analyzed. Results showed that diatoms and there dominant genus were predominately driven by temperature, and the relationship between hydrology and nutrition was insignificant. Distinct relationships were recorded between different diatom genera and temperature over the past eight years. The optimum growth temperature of diatoms and Synedra were both 27℃, while that for Cyclotella and Achnanthes were both 19℃. Low temperature was suitable for the growth of Melosira, and its growth was compromised with increasing temperature. In a multivariable statistical analysis of the dominant diatom genus and the associated environmental factors, we found that the dominant diatom genus responded differently to the associated environmental factors. The total biomass of the diatom and the biomass of Synedra and Achnanthes were significantly and positively correlated with rainfall (P<0.05). The biomass of Cyclotella was significantly and positively correlated with total phosphorus, rainfall, and water level (P<0.05) and significantly and negatively correlated with water exchange rate (P<0.05). The biomass of Melosira was significantly and positively correlated with total phosphorus. The annual peak biomass of diatoms can be predicted by a multiple regression model with independent variables, including rainfall intensity, dissolved total phosphorus, and the accumulated temperature in winter and spring. Our results indicated that the proliferation of diatoms responds significantly to hydrological and meteorological factors while insignificantly to nitrogen and phosphorus loading. External load reduction is needed to maintain a good water quality in the reservoir. In addition, extreme weather conditions should be given attention to provide an early warning for diatom proliferation.

Traditional herbal medicine-derived sulforaphene promotes mitophagic cell death in lymphoma cells through CRM1-mediated p62/SQSTM1 accumulation and AMPK activation.

Sulforaphene (LFS-01) is the major chemical constituent of Raphanus sativus, a medicinal herb used for over a thousand years in traditional Chinese medicine. Here we identified that LFS-01 can selectively eradicate lymphoma cells while sparing normal lymphocytes by triggering concomitant mitophagy and apoptosis. We demonstrated that LFS-01 can retain Nrf2 in the nucleus by covalently modulating CRM1 and consequently upregulate p62/SQSTM1, an essential structural component of the autophagosomes during mitophagic process. We found that LFS-01 treatment also stimulated AMPK and thereby inhibited the mTOR pathway. On the contrary, we revealed that AMPK inhibition can severely impair the LFS-01-mediated mitophagy. Transcriptomic studies confirmed that 15 autophagy-associated genes such as p62/SQSTM1, VCP and BCL2 were differentially expressed after LFS-01 treatment. Furthermore, protein interactome network analysis revealed that the events of apoptosis and the assembly of autophagy vacuole were significant upon LFS-01 exposure. Lastly, we found that LFS-01 exhibited strong efficacy in xenograft mouse model yet with the lack of apparent toxicity to animals. We concluded that LFS-01 triggered mitophagic cell death via CRM1-mediated p62 overexpression and AMPK activation. Our findings provide new insights into the mechanism of action for LFS-01 and highlight its potential applications in treating major human diseases.

Neuroprotection by quercetin via mitochondrial function adaptation in traumatic brain injury: PGC-1α pathway as a potential mechanism.

The aim of this study was to investigate the neuroprotective effects of quercetin in mouse models of traumatic brain injury (TBI) and the potential role of the PGC-1α pathway in putative neuroprotection. Wild-type mice were randomly assigned to four groups: the sham group, the TBI group, the TBI+vehicle group and the TBI+quercetin group. Quercetin, a dietary flavonoid used as a food supplement, significantly reduced TBI-induced neuronal apoptosis and ameliorated mitochondrial lesions. It significantly accelerated the translocation of PGC-1α protein from the cytoplasm to the nucleus. In addition, quercetin restored the level of cytochrome c, malondialdehyde and superoxide dismutase in mitochondria. Therefore, quercetin administration can potentially attenuate brain injury in a TBI model by increasing the activities of mitochondrial biogenesis via the mediation of the PGC-1α pathway.

Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

Traditional Herbal Medicine-Derived Sulforaphene LFS-01 Reverses Colitis in Mice by Selectively Altering the Gut Microbiota and Promoting Intestinal Gamma-Delta T Cells.

Sulforaphene (LFS-01) is a natural compound derived from traditional herbal medicine. Here, we show that oral administration of LFS-01 is able to dramatically alter the skewed gut microbiota and reverse colitis in model mice associated with an increase of intestinal γδT cells. Through 16S rDNA sequencing, we showed that LFS-01 can selectively suppress enteric pathogens such as Escherichia-Shigella and Helicobacter whereas the protective strains including Lactobacillus and Lachnospiraceae were significantly expanded after LFS-01 treatment. Interestingly, we demonstrated that LFS-01 administration can significantly promote the IL-17+γδT cells in model mice in response to the expanded Lactobacillus. We verified that the intracellular components of Lactobacillus can stimulate the growth of IL-17+γδT cells upon preincubation. The increased IL-17A after LFS-01 treatment in turn recovers the disrupted occludin subcellular location and protects the epithelial barrier in the colon of model mice. Remarkably, LFS-01 does not show apparent toxicity to animals and we demonstrated that LFS-01 also exerts strong protective effects in TNBS-induced colitis rats. Therefore, LFS-01 holds great promise for the treatment of inflammatory bowel disease (IBD) and warrants translation for use in clinical trials. Our work provided a new avenue for the treatment of IBD based on the strategy of harnessing intestinal symbiosis.

[Network meta-analysis on selecting Chinese medical injections in radiotherapy for esophageal cancer].

To assess the clinical effect and safety of Chinese traditional medicine injection combined with radiotherapy for esophageal cancer. The relative randomized controlled trials (RCTs) of Chinese medical injections (CMI) combined with radiotherapy as well as simple radiotherapy for esophageal cancer were searched from PubMed, Cochrane Library, EMBASE, Chinese Biomedical Literature Database(CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database and VIP Database as at September 2014. Two researchers completed the data extraction and quality evaluation independently. The data were analyzed by GeMTC 0.14.3 and Stata 12. 0 software. Finally, 43 RCTs involving 3 289 patients were finally included. The star network was constructed by different comparison groups. The results of network meta-analysis showed that the seven CMIs combined with radiotherapy was superior to simple radiotherapy in the treatment of esophageal cancer in efficacy, quality of life, and reduction in the incidence of nausea and leucopenia, but with no significant difference among the seven CMIs. Probability ranking result showed a great possibility for Shenqi Fuzheng and astragalus polysaccharide injections in improving the overall response rate and quality of life, which were followed by cinobufagin and kangai injections. However, only one study was included for Shenqi Fuzheng and astragalus polysaccharide injections. Therefore, cinobufagin or kangai injections were preferred in improving the overall response rate and quality of life. Aidi or compound sophora injections were better than other CMIs in reducing? the incidences of nausea (III-IV) and leukopenia. More RCTs of Shenqi Fuzheng and astragalus polysaccharide injections combined with radiotherapy for patients with esophageal cancer were expected in the future to confirm our results. Moreover, study findings will be reported, particularly for the adverse events in radiotherapy for esophageal cancer.

[Analysis of monosaccharide compositions in polysaccharides from exopleura of Ginkgo biloba].

A high-performance liquid chromatography method of pre-column derivatization with 1-phenyl-3-methyl-5 -pyrazolone (PMP) has been established for determination of 6 kinds of monosaccharides simultaneously. A special Agilent HC-C18 column (4. 6 mm x 250 mm, 5 microm), optimized for the separation of PMP derivatives, was used at ambient temperature of 40 degrees C. The PMP derivatives elution was performed with a mixture of 0.1 mol x L(-1) phosphate buffer (pH 6. 8) and acetonitrile in a ratio of 84: 16 at a flow rate of 1 mL x min(-1), and UV absorbance of the effluent was monitored at 245 nm. The results showed that the polysaccharides from exopleura of Ginkgo biloba were acidic heteropolysaccharides mainly containing mannose, rhamnose, D-galacturonic acid, glucose, galactose, arabinose, with the molar ratio of 0.032: 0.14: 0.296: 0.403:0.106: 0.046.