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.

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.

Magnesium Lithospermate B Attenuates High-Fat Diet-Induced Muscle Atrophy in C57BL/6J Mice.

Magnesium lithospermate B (MLB) is a primary hydrophilic component of Danshen, the dried root of Salvia miltiorrhiza used in traditional medicine, and its beneficial effects on obesity-associated metabolic abnormalities were reported in our previous study. The present study investigated the anti-muscle atrophy potential of MLB in mice with high-fat diet (HFD)-induced obesity. In addition to metabolic abnormalities, the HFD mice had a net loss of skeletal muscle weight and muscle fibers and high levels of muscle-specific ubiquitin E3 ligases, namely the muscle atrophy F-box (MAFbx) and muscle RING finger protein 1 (MuRF-1). MLB supplementation alleviated those health concerns. Parallel changes were revealed in high circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), skeletal TNF receptor I (TNFRI), nuclear factor-kappa light chain enhancer of activated B cells (NF-κB), p65 phosphorylation, and Forkhead box protein O1 (FoxO1) as well as low skeletal phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation. The study revealed that MLB prevented obesity-associated skeletal muscle atrophy, likely through the inhibition of MAFbx/MuRF-1-mediated muscular degradation. The activation of the PI3K-Akt-FoxO1 pathway and inhibition of the TNF-α/TNFRI/NF-κB pathway were assumed to be beneficial effects of MLB.

The Impact of Intraoperative Hypothermia on Blood Loss and Allogenic Blood Transfusion in Total Knee and Hip Arthroplasty: A Retrospective Study.

BACKGROUND: Total joint arthroplasty (TJA) usually leads to substantial blood loss, which may cause allogenic blood transfusion. Hypothermia occurring during operation has been reported to increase blood loss and transfusion rates in nonorthopedic cohorts. However, the relationship between intraoperative hypothermia and blood loss remains controversial in patients undergoing orthopedic surgeries. The aims of this study were to investigate the incidence of hypothermia and identify the impact of intraoperative body temperature and hypothermia on blood loss and transfusion rates in total knee and hip arthroplasty (TKA and THA, respectively). METHODS: This retrospective study enrolled 616 consecutive patients, who underwent primary unilateral TKA or THA at our institution during the period from April 2012 to July 2014. The occurrence of a temperature below 36°C during the operation was documented to identify the incidence of hypothermia. Univariate analysis was performed to find the risk factors for hypothermia. Multiple regression analysis and multivariate logistic regression analysis were employed to explore the association of intraoperative temperature and hypothermia with intraoperative blood loss and perioperative blood transfusion. RESULTS: The incidence of intraoperative hypothermia was 13.5%, 14.0%, and 13.1% in TJA, TKA, and THA, respectively. Intraoperative temperature (P = 0.045, P = 0.006) and hypothermia (P = 0.042, P < 0.001) were associated with intraoperative blood loss and perioperative transfusion in TKA. Intraoperative temperature (P = 0.002) was negatively related to the amount of blood loss, and hypothermia (P = 0.031) was the independent risk factor for transfusion in THA. CONCLUSION: Intraoperative hypothermia is associated with increased blood loss and transfusion rates in TJA. Efforts should be made to maintain normothermia during operation in these patients.

The incidence and risk factors for allogenic blood transfusion in total knee and hip arthroplasty.

BACKGROUND: Excessive blood loss in total joint arthroplasty (TJA) usually leads to an allogenic blood transfusion, which may cause adverse outcomes, prolonged length of hospitalization, and increased costs. The purpose of this study was to determine the incidence and risk factors for intraoperative and postoperative allogenic transfusion in patients undergoing primary unilateral total knee and hip arthroplasty (TKA and THA). METHODS: We conducted a retrospective study and enrolled consecutive patients undergoing primary unilateral TKA and THA at our institution between January 2010 and July 2014 (n = 1534). Information about allogenic transfusion was collected from medical records to determine the incidence. We performed univariate analysis and multivariate logistic regression analysis to identify the independent risk factors. RESULTS: Total, intraoperative, and postoperative transfusion rates were 17.9%, 7.9%, and 11.3%, respectively. The preoperative lower level of hemoglobin (Hb) (P < 0.001) and increased amount of intraoperative blood loss (P < 0.001) were independently associated with transfusion in TKA. The independent risk factors for transfusion in THA were female (P = 0.023), preoperative lower Hb level (P < 0.001), prolonged operation time (P < 0.001), and increased intraoperative blood loss (P < 0.001). CONCLUSIONS: Given the high prevalence and potential risk of transfusion in TJA, interventions for identified risk factors should be used during the perioperative period.

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.

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1-/- mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1-/- only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.

[Effect of xinglong pingchuan recipe on interleukin-5 and the inflammagen related to oxygen free radical in asthmatic mice].

OBJECTIVE: To observe the effect of Xinglong Pingchuan recipe (XLPCR) on interleukin-5 (IL-5), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) in mouse asthma models, and to explore its mechanism in treating asthma. METHODS: The mouse asthma models were established by sensitization and challenge with ovalbumin (OVA). The asthma model was treated with XLPCR. At last, the number of white blood cells and eosinophil was counted, and the concentrations of inflammation factors such as IL-5, SOD, GPx, and MDA in the serum or the lung tissue of each mouse were detected. RESULTS: Compared with the asthmatic group, the number of eosinophil in the XLPCR group decreased significantly (P < 0.01); the concentration of IL-5 in the XLPCR group significantly decreased in the serum or the lung tissue (all P < 0.01); and the concentrations of SOD and GPx in the XLPCR group increased (P < 0.01 and P > 0.05, respectively). On the other hand, the concentration of MDA in the XLPCR group was significantly lower than that of the asthmatic group (P < 0.05). CONCLUSION: XLPCR might inhibit the airway inflammation by decreasing the IL-5 level and adjusting the balance of oxidants/antioxidants.