Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

The alleviating effect of sphingosine kinases 2 inhibitor K145 on nonalcoholic fatty liver.

Sphingosine kinase 2 (SphK2) inhibitors are developed for tumor therapy as considering its anti-tumor effect. Many studies also explored SphK2 modulated glucose and lipid homeostasis, which extended its potential function for metabolic diseases therapy. In this study, we discovered a significant reduction of hepatic lipid accumulation as well as recovery of liver function in ob/ob mice with intraperitoneal injection of K145. Also, db/db mice received K145 showed improvement of both NALFD and hyperglycemia. We furtherly analyzed the genes associated with lipid metabolism and found a remarkable decreased expression of lipogenic genes including FAS, ACC1 and SREBP1c whereas elevated mitochondrial fatty acid ß-oxidation (FAO) related genes expression including CPT1A, MCAD, LCAD, PPAR-α, UCP2. Consistent to in vivo study, in vitro study also confirmed the role of K145 in decreasing lipid accumulation in human HL7702 cells, while inhibiting FAS, ACC1 and SREBP1c mRNA expression. It indicated a possible mechanism of K145 induced improvement of hepatic lipid accumulation partly via inhibition of lipigenesis. Our study suggested a promising role of K145 in drug development for NAFLD and diabetes therapy.

Inhibition of lipogenesis and induction of apoptosis by valproic acid in prostate cancer cells via the C/EBPα/SREBP-1 pathway.

Lipid metabolism reprogramming is now accepted as a new hallmark of cancer. Hence, targeting the lipogenesis pathway may be a potential avenue for cancer treatment. Valproic acid (VPA) emerges as a promising drug for cancer therapy; however, the underlying mechanisms are not yet fully understood. In this study, we aimed to investigate the effects and mechanisms of VPA on cell viability, lipogenesis, and apoptosis in human prostate cancer PC-3 and LNCaP cells. The results showed that VPA significantly reduced lipid accumulation and induced apoptosis of PC-3 and LNCaP cells. Moreover, the expression of CCAAT/enhancer-binding protein α (C/EBPα), as well as sterol regulatory element-binding protein 1 (SREBP-1) and its downstream effectors, including fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and anti-apoptotic B-cell lymphoma 2 (Bcl-2), was markedly decreased in PC-3 and LNCaP cells after VPA administration. Mechanistically, the overexpression of C/EBPα rescued the levels of SREBP-1, FASN, ACC1, and Bcl-2, enhanced lipid accumulation, and attenuated apoptosis of VPA-treated PC-3 cells. Conversely, knockdown of C/EBPα by siRNA further decreased lipid accumulation, enhanced apoptosis, and reduced the levels of SREBP-1, FASN, ACC1, and Bcl-2. In addition, SREBP-1a and 1c enhanced the expressions of FASN and ACC1, but only SREBP-1a had a significant effect on Bcl-2 expression in VPA-treated PC-3 cells. Based on the results, we concluded that VPA significantly inhibits cell viability via decreasing lipogenesis and inducing apoptosis via the C/EBPα/SREBP-1 pathway in prostate cancer cells. Therefore, VPA that targets lipid metabolism and apoptosis is a promising candidate for PCa chemotherapy.

Salvianolic acid B improved insulin resistance through suppression of hepatic ER stress in ob/ob mice.

Impaired insulin sensitivity of insulin-sensitive tissues plays a major role in the pathogenesis of type 2 diabetes, salvianolic acid B (SalB), a natural antioxidant usually treated various cardiovascular diseases was also reported potential utility on diabetes and dyslipidemia. Based on these, we aimed to explored whether the antioxidant effect of SalB play a pivotal role in the molecular mechanisms leading to insulin resistance. We found that SalB improved glucose tolerance and insulin sensitivity, decreased serum ALT, AST and ALP levels of ob/ob mice. Also, transcription of Bip and CHOP, phosphorylation of PERK and IRE1 for endoplasmic reticulum stress (ER) and phosphorylation of IRS-1 for insulin sensitivity in the liver of ob/ob mice were relieved by SalB. Further, SalB decreased phosphorylation of PERK, IRE1 and IRS1 and transcription of Bip and CHOP stimulated by palmitate of hepatic cells HL7702, but did not reversed phosphorylation of JNK and IRS1 and transcription of Bip and CHOP when ER stress was stimulated by tunicamycin. These data shows that SalB improved insulin resistance of ob/ob mice through suppression of hepatic ER stress.

Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial.

OBJECTIVE: To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS: In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS: The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION: Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER: NCT02355795; Results.

3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) ameliorated dexamethasone induced hepatic gluconeogenesis through activation of Akt/FoxO1 pathway.

3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) is identified as a selective SphK2 inhibitor. It was previously reported as an anti-tumor agent, in this study we demonstrated that K145 was able to regulate hepatic gluconeogenesis and improve glucose intolerance in mice. C57BL/6 mice treated with dexamethasone injection were used as experimental animals, which exhibited impaired glucose tolerance and increased gluconeogenetic enzymes. After K145 treatment, we found that the impairment of glucose tolerance and gluconeogenetic genes mRNA expression were improved. Besides, both in vivo and in votro studies suggested that K145 stimulated insulin dependent Akt phosphorylation and subsequently activates FoxO1 phosphorylation therefore inhibited gluconeogenetic genes expression including PEPCK and G6pase. Our study figures out a potential extent increase the value of developing K145 as therapeutic candidate for diabetes.

Pedobacter vanadiisoli sp. nov., isolated from soil of a vanadium mine.

A Gram-stain-negative, light pink, non-motile, rod-shaped, aerobic bacterium, designated strain XNV015T, was isolated from soil of a vanadium mine. Phylogenetic analyses based on 16S rRNA gene sequences indicated that it belongs to the genus Pedobacter and was closely related to Pedobacter suwonensis DSM 18130T (96.93 % sequence similarity), Pedobacter alluvionis NWER-II11T (96.66 %), Pedobacter terrae DS-57T (96.54 %), Pedobacter kyungheensis KACC 16221T (96.54 %) and Pedobacter soli KACC 14939T (96.47 %). This strain clearly differed from the closely related species in terms of acid production from rhamnose and ethanol. Menaquinone-7 was the predominant respiratory quinone. The predominant fatty acids included iso-C15 : 0, C16 : 1ω5c, summed feature 3, iso-C17 : 0 3-OH and C17 : 0 2-OH. The major polar lipids were phosphatidylethanolamine, glycolipids, lipids and aminolipids. The genomic DNA G+C content was 43.8 mol%. The genotypic analysis, biochemical properties, and phenotypic and chemotaxonomic characteristics indicate that strain XNV015T represents a novel species of the genus Pedobacter, for which the name Pedobacter vanadiisoli sp. nov. is proposed. The type strain is XNV015T (=CCTCC AB 2015319T=KCTC 42866T).

Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey.

PURPOSE: Ovarian aging is closely tied to the decline in ovarian follicular reserve and oocyte quality. During the prolonged reproductive lifespan of the female, granulosa cells connected with oocytes play critical roles in maintaining follicle reservoir, oocyte growth and follicular development. We tested whether double-strand breaks (DSBs) and repair in granulosa cells within the follicular reservoir are associated with ovarian aging. METHODS: Ovaries were sectioned and processed for epi-fluorescence microscopy, confocal microscopy, and immunohistochemistry. DNA damage was revealed by immunstaining of γH2AX foci and telomere damage by γH2AX foci co-localized with telomere associated protein TRF2. DNA repair was indicated by BRCA1 immunofluorescence. RESULTS: DSBs in granulosa cells increase and DSB repair ability, characterized by BRCA1 foci, decreases with advancing age. γH2AX foci increase in primordial, primary and secondary follicles with advancing age. Likewise, telomere damage increases with advancing age. In contrast, BRCA1 foci in granulosa cells of primordial, primary and secondary follicles decrease with monkey age. BRCA1 positive foci in the oocyte nuclei also decline with maternal age. CONCLUSIONS: Increased DSBs and reduced DNA repair in granulosa cells may contribute to ovarian aging. Discovery of therapeutics that targets these pathways might help maintain follicle reserve and postpone ovarian dysfunction with age.

No evidence for neo-oogenesis may link to ovarian senescence in adult monkey.

Female germline or oogonial stem cells transiently residing in fetal ovaries are analogous to the spermatogonial stem cells or germline stem cells (GSCs) in adult testes where GSCs and meiosis continuously renew. Oocytes can be generated in vitro from embryonic stem cells and induced pluripotent stem cells, but the existence of GSCs and neo-oogenesis in adult mammalian ovaries is less clear. Preliminary findings of GSCs and neo-oogenesis in mice and humans have not been consistently reproducible. Monkeys provide the most relevant model of human ovarian biology. We searched for GSCs and neo-meiosis in ovaries of adult monkeys at various ages, and compared them with GSCs from adult monkey testis, which are characterized by cytoplasmic staining for the germ cell marker DAZL and nuclear expression of the proliferative markers PCNA and KI67, and pluripotency-associated genes LIN28 and SOX2, and lack of nuclear LAMIN A, a marker for cell differentiation. Early meiocytes undergo homologous pairing at prophase I distinguished by synaptonemal complex lateral filaments with telomere perinuclear distribution. By exhaustive searching using comprehensive experimental approaches, we show that proliferative GSCs and neo-meiocytes by these specific criteria were undetectable in adult mouse and monkey ovaries. However, we found proliferative nongermline somatic stem cells that do not express LAMIN A and germ cell markers in the adult ovaries, notably in the cortex and granulosa cells of growing follicles. These data support the paradigm that adult ovaries do not undergo germ cell renewal, which may contribute significantly to ovarian senescence that occurs with age.

Effects of Chinese heart-healthy diet on blood lipids, glucose, and estimated 10-y cardiovascular disease risk among Chinese adults: results on secondary outcomes of a randomized controlled trial.

BACKGROUND: Healthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown. METHODS: In this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population. RESULTS: Among 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (-0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (-1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (-0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results. CONCLUSIONS: The CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted. This trial was registered at clinicaltrials.gov as NCT03882645.

Effect of lard plus soybean oil on blood pressure and other cardiometabolic risk factors in healthy subjects: a randomized controlled-feeding trial.

Lard has been consumed by humans for thousands of years, but its consumption has declined substantially in the last few decades, because of negative publicity about the consumption of animal-derived saturated fats. Emerging evidence highlights that lard plus soybean oil (blend oil) could be more beneficial for body weight and liver function than the individual use of the two oils. This study aimed to evaluate the effects of blend oil on cardiometabolic risk factors in healthy subjects. This was a parallel, three-arm, randomized controlled-feeding trial. 334 healthy subjects (mean age: 33.1 years, 60% women) were randomized into three isoenergetic diet groups with three different edible oils (30 g day-1) (soybean oil, lard, and blend oil [50% lard and 50% soybean oil]) for 12 weeks. 245 (73.4%) participants completed the study. After the 12-week intervention, reductions in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were greater in the blend oil group than in the other two groups (P = 0.023 and 0.008 for the interaction between the diet group and time, respectively). Reductions of SBP and DBP in the blend oil group were more significant than those in the soybean oil group with P = 0.008 and P = 0.026 and the lard group with P < 0.001 and P < 0.001. Changes in SBP/DBP at 12 weeks were -6.0 (95% CI: -8.6 to -3.4)/0.8 (95% CI: -1.7 to 3.2) mmHg in the blend oil group, -3.3 (95% CI: -5.7 to -0.9)/1.5 (95% CI: -1.0 to 4.0) mmHg in the soybean oil group and -1.2 (95% CI: -3.7 to 1.4)/3.3 (95% CI: 0.9 to 5.8) mmHg in the lard group. Subgroup analyses showed that blend oil significantly decreased SBP and DBP compared with the other two groups in participants with BP ≥ 130/80 mmHg and body mass index ≥25. There were no significant differences in the changes in body weight, waist circumference, serum lipids, or glucose between groups. In conclusion, our findings suggest that blend oil (lard plus soybean oil) reduces BP compared with soybean oil and lard in healthy subjects.

Effect of Lard or Plus Soybean Oil on Markers of Liver Function in Healthy Subjects: A Randomized Controlled-Feeding Trial.

Humans have consumed lard for thousands of years, but in recent decades, it has become much less popular because it is regarded as saturated fat. Animal studies showed that lard plus soybean oil (blend oil) was more advantageous for liver health than using either oil alone. This study aims to assess the effects of blend oil on liver function markers in healthy subjects. The 345 healthy subjects were randomized into 3 isoenergetic diet groups with different edible oils (30 g/day) (soybean oil, lard, and blend oil (50% lard and 50% soybean oil)) for 12 weeks. The reductions in both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were greater in the blend oil group than in the two other groups (p = 0.001 and <0.001 for the interaction between diet group and time, respectively). The reductions in AST and ALT in the blend oil group were more significant compared with those in the soybean oil group (p < 0.001) or lard group (p < 0.001). There were no significant differences in the other liver function markers between the groups. Thus, blend oil was beneficial for liver function markers such as AST and ALT compared with soybean oil and lard alone, which might help prevent non-alcoholic fatty liver disease in the healthy population.

Water Level Has Higher Influence on Soil Organic Carbon and Microbial Community in Poyang Lake Wetland Than Vegetation Type.

Although microorganisms play a key role in the carbon cycle of the Poyang Lake wetland, the relationship between soil microbial community structure and organic carbon characteristics is unknown. Herein, high-throughput sequencing technology was used to explore the effects of water level (low and high levels above the water table) and vegetation types (Persicaria hydropiper and Triarrhena lutarioriparia) on microbial community characteristics in the Poyang Lake wetland, and the relationships between soil microbial and organic carbon characteristics were revealed. The results showed that water level had a significant effect on organic carbon characteristics, and that soil total nitrogen, organic carbon, recombinant organic carbon, particle organic carbon, and microbial biomass carbon were higher at low levels above the water table. A positive correlation was noted between soil water content and organic carbon characteristics. Water level and vegetation type significantly affected soil bacterial and fungal diversity, with water level exerting a higher effect than vegetation type. The impacts of water level and vegetation type were higher on fungi than on bacteria. The bacterial diversity and evenness were significantly higher at high levels above the water table, whereas an opposite trend was noted among fungi. The bacterial and fungal richness in T. lutarioriparia community soil was higher than that in P. hydropiper community soil. Although both water level and vegetation type had significant effects on bacterial and fungal community structures, the water level had a higher impact than vegetation type. The bacterial and fungal community changes were the opposite at different water levels but remained the same in different vegetation soils. The organic carbon characteristics of wetland soil were negatively correlated with bacterial diversity but positively correlated with fungal diversity. Soil water content, soluble organic carbon, C/N, and microbial biomass carbon were the key soil factors affecting the wetland microbial community. Acidobacteria, Alphaproteobacteria, Verrucomicrobia, Gammaproteobacteria, and Eurotiomycetes were the key microbiota affecting the soil carbon cycle in the Poyang Lake wetland. Thus, water and carbon sources were the limiting factors for bacteria and fungi in wetlands with low soil water content (30%). Hence, the results provided a theoretical basis for understanding the microbial-driven mechanism of the wetland carbon cycle.

Identification of alternatively spliced Dab1 and Fyn isoforms in pig.

BACKGROUND: Disabled-1 (Dab1) is an adaptor protein that is essential for the intracellular transduction of Reelin signaling, which regulates the migration and differentiation of postmitotic neurons during brain development in vertebrates. Dab1 function depends on its tyrosine phosphorylation by Src family kinases, especially Fyn. RESULTS: We have isolated alternatively spliced forms of porcine Dab1 from brain (sDab1) and liver (sDab1-Li) and Fyn from brain (sFyn-B) and spleen (sFyn-T). Radiation hybrid mapping localized porcine Dab1 (sDab1) and Fyn (sFyn) to chromosomes 6q31-35 and 1p13, respectively. Real-time quantitative RT-PCR (qRT-PCR) demonstrated that different isoforms of Dab1 and Fyn have tissue-specific expression patterns, and sDab1 and sFyn-B display similar temporal expression characteristics in the developing porcine cerebral cortex and cerebellum. Both sDab1 isoforms function as nucleocytoplasmic shuttling proteins. It was further shown that sFyn phosphorylates sDab1 at tyrosyl residues (Tyr) 185, 198/200 and 232, whereas sDab1-Li was phosphorylated at Tyr 185 and Tyr 197 (corresponding to Y232 in sDab1) in vitro. CONCLUSIONS: Alternative splicing generates natural sDab1-Li that only carries Y185 and Y197 (corresponding to Y232 in sDab1) sites, which can be phosphorylated by Fyn in vitro. sDab1-Li is an isoform that is highly expressed in peripheral organs. Both isoforms are suggested to be nucleocytoplasmic shuttling proteins. Our results imply that the short splice form sDab1-Li might regulate cellular responses to different cell signals by acting as a dominant negative form against the full length sDab1 variant and that both isoforms might serve different signaling functions in different tissues.

Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model.

Sepsis is considered as a life-threatening organ dysfunction caused by a dysregulated response of the host to an infection. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition, and is the type of organ injury that is most commonly induced by sepsis. Resveratrol (RSV) has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties. The present study aimed to investigate whether RSV could mitigate sepsis-induced ALI/ARDS, and also to unravel the underlying mechanism. The model of sepsis was established by applying the cecal ligation and puncture (CLP) method, and mitochondria from the lung tissue were isolated to assess mitochondrial function, as determined from measuring mitochondrial superoxide production using MitoSOX red mitochondrial superoxide indicator and the membrane potential. It was found that RSV could exert a protective role in CLP-induced ALI/ARDS, as evidenced by moderate levels of inflammatory cell infiltration and interstitial edema, as well as decreased levels of C-reactive protein (P<0.01), interleukin (IL)-6 (P<0.01), IL-1ß (P<0.01) and tumor necrosis factor-α (P<0.01). Moreover, phospholipid scramblase 3 (PLSCR-3)-mediated mitochondrial dysfunction and mitophagy were shown to contribute towards the CLP-caused lung damage, which was reversed upon RSV administration, as demonstrated by improved mitochondrial function and markedly reduced increases in the protein levels of autophagy related (ATG)5 (P<0.01), ATG7 (P<0.05) and microtubule-associated protein 1A/1B-light chain 3 (LC3-Ⅰ/Ⅱ) (P<0.01), and a significantly increased expression of P62 (P<0.05). In addition, with regard to the CLP-induced lung injury in the mouse model, overexpression of PLSCR-3 was found to remove the beneficial effects observed upon RSV treatment. Taken together, the results of the present study have uncovered a novel molecular mechanism through which RSV may alleviate ALI/ARDS via regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in CLP-induced mouse model.

Dexmedetomidine protects the heart against ischemia reperfusion injury via regulation of the bradykinin receptors.

BACKGROUND: Dexmedetomidine (DEX) has been reported to protect the heart against ischemia reperfusion (I/R) injury. However, the exact mechanisms are still not fully understood. METHODS AND RESULTS: A rat cardiac I/R injury model was induced by ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion for 2 h, and DEX was administered intravenously 30 min before ischemia. We confirmed that DEX treatment mitigated cardiac I/R injury. Interestingly, we found that DEX regulated the expression of bradykinin (BK) receptors (B1R and B2R) in rat hearts during I/R injury and enhanced the protective action of BK administered during reperfusion. Moreover, in vitro hypoxia reoxygenation (H/R) injury was induced in neonatal rat cardiomyocytes (CMs), and DEX was administered 1 h before hypoxia. The in vitro findings were consistent with the in vivo experiments. We found that an α2-adrenoceptor (α2-AR) antagonist (yohimbine) completely aborted DEX-induced B1R and B2R regulation; an adenylyl cyclase (AC) agonist (forskolin) blocked B1R downregulation, while a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) blocked B2R upregulation. The above findings indicated that DEX interacted with α2-AR in cardiomyocytes, inhibited B1R expression via suppression of AC, and stimulated B2R expression via activation of PI3K. CONCLUSIONS: DEX regulates BK receptor expression and potentiates the protection of BK in cardiac I/R injury, which suggests that modulating endogenous cardioprotective factors may play an important role in DEX-induced cardioprotection.

Comparison of the expression of cytokine genes in the bursal tissues of the chickens following challenge with infectious bursal disease viruses of varying virulence.

BACKGROUND: Cytokines are important mediators and regulators of host responses against foreign antigen, with their main function to orchestrate the functional activities of the cells of the immune system. However little is known about the role of cytokines in pathogenesis and immune responses caused by infectious bursa disease virus (IBDV). The aim of this study was to examine the transcripts of cell-mediated immune response-related cytokine genes in the bursal tissues of chickens infected with IBDVs of varying virulence to gain an understanding of pathological changes and mechanisms of immunosuppression caused by IBDV infection and the immune responses evoked. RESULTS: Real-time quantitative PCR analysis revealed that the expression levels of both Th1 [interferon (IFN)-γ, interleukins (IL)-2 and IL-12p40] and Th2 (IL-4, IL-5, IL-13 and IL-10) cytokines were significantly up-regulated following challenge with the H strain (vvIBDV) and up to 2- and 30-fold, respectively (P < 0.05). Following infection with the Ts strain (cell-adapted virus) these cytokine transcripts were up-regulated at 5 days post-infection (dpi), 2- and 13-fold respectively (P < 0.05), while the expression levels of IL-2 and IL-4 were not significantly different (P > 0.05). A higher degree of cytokine expression was induced by the H strain compared with the Ts strain. CONCLUSION: The results indicate that the expression of cell-mediated immune-related cytokine genes is strongly induced by IBDV, especially by the vvIBDV, H strain and reveal that these cytokines could play a crucial role in driving cellular immune responses during the acute phase of IBDV infection, and the cellular immune responses caused by IBDV of varying virulence are through different signaling pathways.

The Compensatory Tillering in the Forage Grass Hordeum brevisubulatum After Simulated Grazing of Different Severity.

The response of compensatory growth is an important adaptive strategy for plants to grazing. However, most previous studies on compensatory growth of plants focused on the compensation of the biomass or the number of sexual reproductive offspring and neglected the compensatory growth of vegetative reproduction (VR). This is important not only for plant compensatory growth studies, but also for theoretical and practical studies of grassland production. The clonal tussock grass Hordeum brevisubulatum was selected as the research object. Four different clipping severities (unclipping and clipping stubble at heights of 15, 10, and 5 cm) at the jointing stage and flowering stage were implemented to study the effect of simulated grazing. To explore the effect of recovery growth time on plant growth after simulated grazing, three sampling times were used at different recovery times after simulated grazing (1, 3, and 7 weeks). We found that light and moderate grazing severity significantly increased the number of vegetative reproduction modules, the promotion of simulated grazing on the number of vegetative reproduction modules was higher in the jointing stage than the flowering stage, and the increase in simulated grazing severity decreased with prolonged recovery growth time. The number of tillers significantly decreased with the increase in simulated grazing in both the jointing and flowering stages at 1 week after damage, and the decreasing effect weakened with the prolonged recovery growth time. The bud number mainly showed over-compensation, the juvenile tiller number showed complete compensation, and the tiller number showed under-compensation at 1 and 3 weeks after recovery growth. The number of tillers showed complete compensation under different grazing severities in the jointing stage, while it showed under-compensation in the flowering stage at 7 weeks after recovery growth. Our results indicated that different grazing severities in the jointing stage could promote the output of tillers with matter production capacity from vegetative reproduction modules, as well as improve the capability of compensatory growth. Therefore, in plant production, there will be a sustainable development effect on the renewal and productivity of the H. brevisubulatum population, resulting in different grazing severities in the jointing stage.

Overweight and underweight status are linked to specific gut microbiota and intestinal tricarboxylic acid cycle intermediates.

BACKGROUND & AIMS: Intestinal short-chain fatty acids have been demonstrated to modulate host energy metabolism and are elevated in overweight and obese individuals. We hypothesized that other intestinal energy products especially tricarboxylic acid (TCA) cycle intermediates might also related to overweight status. In addition, little information is available regarding to the potential relationship between gut microbiota and underweight status. Therefore, the aim of this study was to investigate whether gut microbiota and intestinal energy metabolites differ in underweight, normal weight, and overweight individuals, and their correlations with host cardiometabolic risk factors. SUBJECTS/METHODS: Gut microbiome, intestinal energy metabolites, circulating cardiometabolic risk factors, and proinflammatory markers were determined in 29 underweight, 67 normal weight, and 67 overweight adults. RESULTS: The fecal concentrations of succinic acid, fumaric acid, malic acid, propionic acid, and adipic acid were significantly increased in the overweight individuals in parallel with a higher relative abundance of Veillonellacea after adjusting for multiple comparisons (all p < 0.05). The intestinal concentration of TCA cycle intermediate succinic acid was positively associated with body weight (r = 0.28, p = 0.04), and malic acid were in positive association with circulating total cholesterol, low-density lipoprotein cholesterol, and interleukin-1ß (all r > 0.25, p < 0.05). Compared with the normal weight individuals, the gut microbial α-diversity was lower in the overweight (p = 0.007 for Shannon index and p = 0.009 for Ace index) and underweight (p = 0.05 for Shannon index and p = 0.08 for Ace index) groups. However, no significant differences in the overall gut microbiota composition were observed among the three groups. CONCLUSIONS: Our findings revealed that low gut microbiota diversity was associated with both overweight and underweight status. Intestinal TCA cycle intermediates were associated with overweight development and might be potential markers for future studies related to gut microbiota and host cardiometabolic health.

Contribution of diet to gut microbiota and related host cardiometabolic health: diet-gut interaction in human health.

Obesity and cardiometabolic diseases in both developed and developing counties in a state of nutrition transition are often related to diet, which also play a major role in shaping human gut microbiota. The human gut harbors diverse microbes that play an essential role in the well-being of their host. Complex interactions between diet and microorganisms may lead to beneficial or detrimental outcomes to host cardiometabolic health. Despite numerous studies using rodent models indicated that high-fat diet may disrupt protective functions of the intestinal barrier and contribute to inflammatory processes, evidence from population-based study is still limited. In our recent study of a 6-month randomized controlled-feeding trial, we showed that high-fat, low-carbohydrate diet was associated with unfavorable changes in gut microbiota, fecal microbial metabolites, and plasma proinflammatory factors in healthy young adults. Here, we provide an overview and extended discussion of our key findings, and outline important future directions.