Observational study on the potential mechanism of Sanao decoction in the treatment of asthma based on network pharmacology and molecular docking.

Bronchial asthma (BA) is a chronic respiratory disease closely related to immune system dysregulation. Traditional Chinese medicine has long adopted the strategy of Sanao decoction in the treatment of bronchial asthma. However, due to the multi-target and multi-pathway characteristics of Chinese herbal medicine, we are still unclear about the specific mechanism of Sanao decoction in treating bronchial asthma. To investigate the mechanism of action of Sanao decoction in the treatment of BA using a network pharmacology approach and preliminary validation by molecular docking technology. Traditional Chinese medicine systems pharmacology database and analysis platform and UniProt databases were used to search the active ingredients and targets of Sanao decoction, and BA-related targets were screened according to GeneCards and online Mendelian inheritance in man database databases. The intersection targets were imported into the STRING database to construct a protein-protein interaction network, and Cytoscape 3.9.1 software was used to screen out hub genes. This study also constructed a "drug-ingredient-target" visual network diagram. Gene Ontology and Kyoto Encyclopedia of Genomes enrichment analysis was performed on targets in the protein-protein interaction network using the ClusterProfiler package in R, with a P value < .05. Autodock software was used for molecular docking to complete the preliminary verification of core components and targets. A total of 73 active compounds and 308 targets of Sanao decoction, including 1640 BA-related disease targets, were retrieved from mainstream databases. Gene Ontology analysis and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that Sanao decoction plays a role in the treatment of BA through signaling pathways such as PI3K-Akt, MAPK, and IL-17 signaling pathway. The 9 core goals represent the main elements related to Sanao decoction in the treatment of BA. Subsequently, the molecular docking results showed that most of the active compounds of Sanao decoction have strong binding efficiency with the hub gene. Sanao decoction has a key impact on BA through multiple channels. In summary, this intricate network reflects the potential of Sanao decoction in treating BA, a multifactorial disease. In addition, this study laid the foundation for further in vivo and in vitro experimental research and expanded the clinical application of Sanao decoction.

Protective Role of Endothelial SIRT1 in Deep Vein Thrombosis and Hypoxia-induced Endothelial Dysfunction Mediated by NF-κB Deacetylation.

Venous hypoxia is considered as the major pathogenetic mechanism linking blood flow stagnancy with deep vein thrombosis (DVT). Our previous study showed that activating SIRT1 may attenuate inferior vena cava (IVC) stenosis-induced DVT in rats. This study was aimed to investigate the role of endothelial SIRT1 in DVT and hypoxia-induced endothelial dysfunction as well as the underlying mechanism. Protein profiling of IVCs and blood plasma of DVT rats induced by IVC stenosis was analysed by 4D Label free proteomics analysis. To verify the independent role of SIRT1 in DVT and oxygen-glucose deprivation (OGD)-induced endothelial dysfunction, SIRT1 specific activator SRT1720 and SIRT1 knockdown in both local IVCs and endothelial cells were employed. Moreover, the role of the NF-κB were investigated using NF-κB inhibitor caffeic acid phenethyl ester (CAPE). SRT1720 significantly inhibited thrombus burden, leukocytes infiltration, protein expressions of cell adhesion molecules and chemokines, as well as acetylation level of NF-κB/p65 in wild DVT rats, while these protective effects of SRT1720 were abolished in rats with SIRT1 knockdown in local IVCs. In vitro, SRT1720 protected endothelial cells against OGD-induced dysfunction characterized with enhanced adhesion of monocytes as well as the protein expressions of cell adhesion molecules and chemokines, whereas these protective effects of SRT1720 were vanished by SIRT1 stable knockdown. Furthermore, CAPE attenuated endothelial cell dysfunction and abolished these effects of SIRT1 knockdown. Collectively, these data suggested that endothelial SIRT1 plays an independent role in ameliorating hypoxia-induced endothelial dysfunction and thrombotic inflammation in DVT, and this effect is mediated by NF-κB deacetylation.

Temporary Upregulation of Nrf2 by Naringenin Alleviates Oxidative Damage in the Retina and ARPE-19 Cells.

Dry age-related macular degeneration (dAMD) is a chronic degenerative ophthalmopathy that leads to serious burden of visual impairment. Antioxidation in retinal pigment epithelium (RPE) cells is considered as a potential treatment for dAMD. Our previous studies have showed that naringenin (NAR) protects RPE cells from oxidative damage partly through SIRT1-mediated antioxidation. In this study, we tested the hypothesis that the Nrf2 signaling is another protective mechanism of NAR on dAMD. NaIO3-induced mouse retinopathy and ARPE-19 cell injury models were established. Immunochemical staining, immunofluorescence, and western blotting were performed to detect the protein expressions of Nrf2 and HO-1. In addition, ML385 (activity inhibitor of Nrf2) and zinc protoporphyrin (ZnPP, activity inhibitor of HO-1) were applied to explore the effect of NaIO3 or NAR. The results showed that NAR increased the protein expressions of Nrf2 and HO-1 in the retinas in mice exposed to NaIO3 at the early stage. NAR treatment also resulted in a stronger activation of Nrf2 at the early stage in NaIO3-treated ARPE-19 cells. Moreover, inhibition of HO-1 by ZnPP weakened the cytoprotective effect of NAR. The constitutive accumulation and activation of Nrf2 induced by NaIO3 led to the death of RPE cells. However, NAR decreased the protein expressions of Nrf2 and HO-1 towards normal level in the mouse retinas and ARPE-19 cells exposed to NaIO3 at the late stage. Our findings indicate that NAR protects RPE cells from oxidative damage via activating the Nrf2 signaling pathway.

Naringenin protects RPE cells from NaIO3-induced oxidative damage in vivo and in vitro through up-regulation of SIRT1.

BACKGROUND: Dry age-related macular degeneration (dAMD) leads to serious burden of visual impairment and there is no definitive treatment. Previous studies have showed that naringenin (NAR) significantly increased electroretinography (ERG) c-wave in sodium iodate (NaIO3)-treated rats and viability of NaIO3-treated ARPE-19 cells. But the underlying mechanism is still unknown. PURPOSE: We tested the hypothesis that anti-oxidation mediated by Sirtuin 1 (SIRT1) was important to the protective effect of NAR on dAMD. STUDY DESIGN/METHODS: NaIO3-induced mice retinopathy and ARPE-19 cells injury models were established. In vivo, the protective effect of NAR eye drops on retina was evaluated by flash ERG (FERG) recording and histopathological examination. In vitro, viability of ARPE-19 cells, and the levels of lactic dehydrogenase (LDH), reactive oxygen species (ROS) and carbonyl protein were detected. Protein expression of SIRT1 was analyzed by immunochemical staining, immunofluorescence and western blotting. RESULTS: NAR eye drops improved retinal function and morphology and normalized the protein expression of SIRT1 in mice exposed to NaIO3. NAR promoted the survival of ARPE-19 cells in a concentration-dependent manner. NAR up-regulated SIRT1 protein expression, and decreased levels of ROS and carbonyl protein. Moreover, EX527, a selective inhibitor of SIRT1, abolished the effects of NAR on the cell viability and ROS. In addition, SRT1720, a selective agonist of SIRT1, improved the viability of cells and suppressed the production of ROS. CONCLUSION: Our findings indicate that SIRT1-mediated anti-oxidation contributes to the protective effect of NAR eye drops on dAMD.

Spatholobi Caulis dispensing granule reduces deep vein thrombus burden through antiinflammation via SIRT1 and Nrf2.

BACKGROUND: Deep vein thrombosis (DVT) is a kind of blood stasis syndrome. Spatholobi Caulis (SC) has been widely used for the treatment of blood stasis syndrome in China, but the underlying mechanism remains poorly understood. PURPOSE: The aim of present study was to investigate the anti-DVT mechanism of Spatholobi Caulis dispensing granule (SCDG). STUDY DESIGN/METHODS: A rat model of inferior vena cava (IVC) stenosis-induced DVT and a cell model of oxygen-glucose deprivation (OGD) were performed. Rats were orally administered with SCDG solution once daily for seven consecutive days. IVC stenosis-induced DVT was operated on the sixth day. Thrombi were harvested and weighed on the seventh day. Pathological changes were observed by hematoxylin-eosin (HE) staining. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß of serum were analyzed by enzyme-linked immunosorbent assay. C-reactive protein (CRP) was measured with turbidimetric immunoassay. Protein expressions in thrombosed IVCs and/or OGD-stimulated EA. hy926 cells were evaluated by western blot and/or immunofluorescence analyses. RESULTS: SCDG dramatically decreased thrombus weight. SCDG decreased tissue factor (TF) protein expression, inflammatory cells influxes in thrombosed vein wall and serum levels of inflammatory cytokines and CRP. Further, SCDG up-regulated Sirtuin 1 (SIRT1) protein expression and down-regulated acetylated-NF-κB p65 (Ace-p65) protein expression. Moreover, SCDG up-regulated nuclear factor-erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions, and down-regulated phosphorylated-NF-κB p65 (p-p65) protein expression. In the OGD cell model, SCDG medicated serum decreased the protein expression of TF. SCDG medicated serum enhanced SIRT1 protein expression and reduced Ace-p65 nuclear protein expression. SCDG medicated serum promoted protein expressions of nuclear Nrf2 and total HO-1, and inhibited translocation of p65. Furthermore, inhibiting SIRT1 and Nrf2 reversed the protective effect of SCDG medicated serum on OGD-induced EA. hy926 cells. CONCLUSION: SCDG may prevent DVT through antiinflammation via SIRT1 and Nrf2.

Inferior vena cava stenosis-induced deep vein thrombosis is influenced by multiple factors in rats.

BACKGROUND: The pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring reliable animal models. Inferior vena cava (IVC) stenosis model mimics human DVT. OBJECTIVE: To provide optimal conditions for establishing a rat model of IVC stenosis-induced DVT. METHODS: Effects of suture, and body weight, sex and side branches of rats on the IVC stenosis model were evaluated. 1 d after modeling, the weight and length of thrombosed IVCs and side branch distance were measured. Histopathological change and leukocytes influxes were observed by hematoxylin and eosin staining. Ly-6G-positive neutrophils were located by immunofluorescence. A multiple regression linear model was then built. RESULTS: IVCs stenosed with silk or monofilament sutures presented no difference in leukocyte influxes. Thrombus of 220-340 g rats was significantly heavier than that of 180-220 g rats. Although no statistic difference was found in thrombus weight between male and female rats weighing 180-260 g, males weighing 260-300 g formed larger thrombi than weight-matched females. Thrombus weight and length of rats except 180-220 g females was not impacted by side branch ligation and side branch distance. The regression model showed that sex and body weight were key factors affecting thrombus weight. CONCLUSIONS: Male and female rats weighing 220-260 g are more suitable for establishing a model of DVT induced by stenosing IVC with silk and without side branch ligation.

Laparoscopic versus open pancreatoduodenectomy: a meta-analysis of randomized controlled trials

INTRODUCTION: the evidence with regard to the benefit of laparoscopic surgery for pancreatoduodenectomy is conflicting. The aim of this meta-analysis was to compare the short-term outcomes in patients undergoing laparoscopic or open pancreatoduodenectomy via randomized controlled trial studies. METHODS: PubMed, Embase and Cochrane Library databases were searched for studies addressing laparoscopic versus open pancreatoduodenectomy up to February 2019. Only randomized controlled trial studies were included. RESULTS: three randomized controlled trial studies were identified, which included a total of 224 patients. Statistically significant differences were found with regard to estimated blood loss in favor of laparoscopic pancreatoduodenectomy (WMD, -150.9 ml; 95% CI, -167.61 to -134.18; p < 0.001) but with longer operative time (WMD, 97.66 min; 95% CI, 21.28 to 174.05; p = 0.01). No significant differences were found for severe postoperative complications (defined as Clavien-Dindo grade ≥ III complications), complication-related mortality within 90 days, blood transfusion requirements, length of hospital stay, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, surgical site infection, readmission rate, reoperation rate, harvested lymph nodes and R0 resection rate. CONCLUSIONS: the perioperative safety of laparoscopic pancreatoduodenectomy, which may have an advantage of lower estimated blood loss, is comparable to that of open pancreatoduodenectomy. Currently, a small volume of cases may be an important reason that affects the evaluation between laparoscopic and open pancreatoduodenectomy. Further evaluation of laparoscopic pancreatoduodenectomy will require large randomized control trials

No disponible

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway.

BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.

Laparoscopic versus open pancreatoduodenectomy: a meta-analysis of randomized controlled trials.

INTRODUCTION: the evidence with regard to the benefit of laparoscopic surgery for pancreatoduodenectomy is conflicting. The aim of this meta-analysis was to compare the short-term outcomes in patients undergoing laparoscopic or open pancreatoduodenectomy via randomized controlled trial studies. METHODS: PubMed, Embase and Cochrane Library databases were searched for studies addressing laparoscopic versus open pancreatoduodenectomy up to February 2019. Only randomized controlled trial studies were included. RESULTS: three randomized controlled trial studies were identified, which included a total of 224 patients. Statistically significant differences were found with regard to estimated blood loss in favor of laparoscopic pancreatoduodenectomy (WMD, -150.9 ml; 95% CI, -167.61 to -134.18; p < 0.001) but with longer operative time (WMD, 97.66 min; 95% CI, 21.28 to 174.05; p = 0.01). No significant differences were found for severe postoperative complications (defined as Clavien-Dindo grade ≥ III complications), complication-related mortality within 90 days, blood transfusion requirements, length of hospital stay, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, surgical site infection, readmission rate, reoperation rate, harvested lymph nodes and R0 resection rate. CONCLUSIONS: the perioperative safety of laparoscopic pancreatoduodenectomy, which may have an advantage of lower estimated blood loss, is comparable to that of open pancreatoduodenectomy. Currently, a small volume of cases may be an important reason that affects the evaluation between laparoscopic and open pancreatoduodenectomy. Further evaluation of laparoscopic pancreatoduodenectomy will require large randomized control trials.

Transanal versus laparoscopic total mesorectal excision for mid and low rectal cancer: a meta-analysis of short-term outcomes.

INTRODUCTION: The benefit of transanal total mesorectal excision (TaTME) for mid and low rectal cancer is conflicting. AIM: To assess and compare the short-term outcomes of TaTME with conventional laparoscopic total mesorectal excision (LaTME) for middle and low rectal cancer. MATERIAL AND METHODS: We searched PubMed, Embase and Cochrane Library databases for studies addressing TaTME versus conventional LaTME for rectal cancer between 2008 and December 2018. Randomized controlled trials (RCTs) and retrospective studies which compared TaTME with LaTME were included. RESULTS: Twelve retrospective case-control studies were identified, including a total of 899 patients. We did not find significant differences in overall intraoperative complications, blood loss, conversion rate, operative time, overall postoperative complication, anastomotic leakage, ileus, or urinary morbidity. Also no significant differences in oncological outcomes including circumferential resection margin (CRM), positive CRM, distal margin distance (DRM), positive DRM, quality of mesorectum, number of harvested lymph nodes, temporary stoma or local recurrence were found. Although the TaTME group had better postoperative outcomes (readmission, reoperation, length of hospital stay) on average, the difference did not reach statistical significance. CONCLUSIONS: Transanal total mesorectal excision offers a safe and feasible alternative to LaTME although the clinicopathological features were not superior to LaTME in this study. Currently, with the lack of evidence on benefits of TaTME, further evaluation of TaTME requires large randomized control trials to be conducted.

Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown. OBJECTIVE: The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway. METHODS: Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK. RESULTS: DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527. CONCLUSION: DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.

Deep Vein Thrombosis is Modulated by Inflammation Regulated via Sirtuin 1/NF-κB Signalling Pathway in a Rat Model.

BACKGROUND: Inflammation plays an important role in thrombus formation, and Sirtuin 1 (SIRT1) negatively regulates inflammation via deacetylating nuclear factor-kappa B. However, the relationship between SIRT1-regulated inflammation and deep vein thrombosis (DVT) is still unknown. OBJECTIVE: The aim of this study was to investigate whether SIRT1 plays a critical role in inferior vena cava (IVC) stenosis-induced DVT. MATERIALS AND METHODS: Thrombus weight and histopathologic analysis of IVC were evaluated at different time points after IVC stenosis in rats. Serum levels of inflammatory cytokines and protein expressions of SIRT1, acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF) in thrombosed IVC were assessed. Besides, the effects of resveratrol (RES, a SIRT1 agonist) and EX527 (a selective SIRT1 inhibitor) on DVT were evaluated. RESULTS: Thrombus weight was increased from 1 to 3 days after IVC stenosis, and then was decreased afterwards. Leukocytes infiltration appeared and serum levels of cytokines were significantly increased in rats of IVC stenosis. SIRT1 protein expression was significantly down-regulated at 1 hour and 1 day after stenosis, while p-p65, Ace-p65 and TF protein expressions appeared a contrary trend. RES reduced thrombus weight, leukocytes infiltration, levels of tumour necrosis factor-α and interleukin-1ß and protein expressions of Ace-p65 and TF as well. Moreover, RES significantly increased the protein and messenger ribonucleic acid expressions of SIRT1, while EX527 abolished the protective effects of RES. CONCLUSION: SIRT1 activation attenuated IVC stenosis-induced DVT via anti-inflammation in rats. Therefore, SIRT1 may be a potential therapeutic target that could ameliorate DVT.

Composition Analysis and Feature Selection of the Oral Microbiota Associated with Periodontal Disease.

Periodontitis is an inflammatory disease involving complex interactions between oral microorganisms and the host immune response. Understanding the structure of the microbiota community associated with periodontitis is essential for improving classifications and diagnoses of various types of periodontal diseases and will facilitate clinical decision-making. In this study, we used a 16S rRNA metagenomics approach to investigate and compare the compositions of the microbiota communities from 76 subgingival plagues samples, including 26 from healthy individuals and 50 from patients with periodontitis. Furthermore, we propose a novel feature selection algorithm for selecting features with more information from many variables with a combination of these features and machine learning methods were used to construct prediction models for predicting the health status of patients with periodontal disease. We identified a total of 12 phyla, 124 genera, and 355 species and observed differences between health- and periodontitis-associated bacterial communities at all phylogenetic levels. We discovered that the genera Porphyromonas, Treponema, Tannerella, Filifactor, and Aggregatibacter were more abundant in patients with periodontal disease, whereas Streptococcus, Haemophilus, Capnocytophaga, Gemella, Campylobacter, and Granulicatella were found at higher levels in healthy controls. Using our feature selection algorithm, random forests performed better in terms of predictive power than other methods and consumed the least amount of computational time.

Antioxidant and anti­inflammatory effects of DHK­medicated serum on high glucose­induced injury in endothelial cells.

It has been shown that oxidative damage and inflammation caused by hyperglycemia in endothelial cells are key factors triggering diabetic vascular complications. The aim of the present study was to investigate the antioxidant and anti­inflammatory effects of Danhong Huayu Koufuye (DHK)­medicated serum on high glucose (HG)­induced injury in endothelial cells, and examine its underlying mechanisms. EA. hy926 cells were treated with normal glucose, HG, or HG with DHK­medicated serum. Cell viability was assessed using the MTT method. Apoptosis was detected using flow cytometry. Intracellular reactive oxygen species (ROS) levels were measured using the 2',7'­dichlorodihydrofluorescein method. Cell culture supernatant was collected for detecting the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA). The protein expression levels of intercellular adhesion molecule­1 (ICAM­1), nuclear factor­κB (NF­κB), hypoxia­inducible factor­1α (HIF­1α) and vascular endothelial growth factor (VEGF) were determined using western blot analysis. The results revealed that DHK­medicated serum accelerated the proliferation and inhibited the apoptosis of cells treated with HG (P<0.01) in a dose­dependent manner. Compared with the HG group, the high levels of ROS and MDA were significantly reduced by DHK­medicated serum (P<0.01). A 10% concentration of DHK­medicated serum increased the activities of SOD and GPx by 59.4 and 95.5%, respectively. The high protein expression levels of ICAM­1, NF­κB, VEGF and HIF­1α were significantly ameliorated by DHK­medicated serum (P<0.01, vs. HG group). These findings indicated that DHK­medicated serum protected EA. hy926 cells from HG­induced injury and apoptosis through antioxidation and anti­inflammatory effects.

Bacterial diversity among four healthcare-associated institutes in Taiwan.

Indoor microbial communities have important implications for human health, especially in health-care institutes (HCIs). The factors that determine the diversity and composition of microbiomes in a built environment remain unclear. Herein, we used 16S rRNA amplicon sequencing to investigate the relationships between building attributes and surface bacterial communities among four HCIs located in three buildings. We examined the surface bacterial communities and environmental parameters in the buildings supplied with different ventilation types and compared the results using a Dirichlet multinomial mixture (DMM)-based approach. A total of 203 samples from the four HCIs were analyzed. Four bacterial communities were grouped using the DMM-based approach, which were highly similar to those in the 4 HCIs. The α-diversity and ß-diversity in the naturally ventilated building were different from the conditioner-ventilated building. The bacterial source composition varied across each building. Nine genera were found as the core microbiota shared by all the areas, of which Acinetobacter, Enterobacter, Pseudomonas, and Staphylococcus are regarded as healthcare-associated pathogens (HAPs). The observed relationship between environmental parameters such as core microbiota and surface bacterial diversity suggests that we might manage indoor environments by creating new sanitation protocols, adjusting the ventilation design, and further understanding the transmission routes of HAPs.

Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation.

Danhong Huayu Koufuye (DHK), a traditional Chinese prescription, is used to treat central retinal vein occlusion clinically. We previously reported that DHK prevented diabetic retinopathy (DR) in rats. Moreover, we found that it protected endothelial cells from hyperglycemia-induced apoptosis through antioxidation and anti-inflammation. Here, we investigated whether antioxidative and anti-inflammatory activities of DHK contributed to its therapeutic effect on DR in streptozotocin- (STZ-) induced diabetic rats. DHK significantly blocked the breakdown of the blood-retinal barrier (BRB) and increased the thickness of the inner nuclear layer (INL), as well as suppressed the swelling of the ganglion cell layer (GCL) in diabetic retinas. DHK remarkably increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in plasma, and decreased serum level of nitric oxide (NO). Moreover, DHK markedly reduced the serum levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, DHK significantly downregulated protein expressions of VEGF and inducible NO synthase (iNOS) and mRNA expression of ICAM-1 in retinas. These results suggest that the antioxidative and anti-inflammatory activities of DHK may be important mechanisms involved in the protective effect of DHK on DR in STZ-induced diabetic rats.

Danhong huayu koufuye prevents deep vein thrombosis through anti-inflammation in rats.

BACKGROUND: Danhong huayu koufuye (DHK) has traditionally been used clinically for a long time in China. This study was to evaluate the effect of DHK in treating deep vein thrombosis (DVT) in rats and explore its possible mechanism. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups, performed with incomplete inferior vena cava ligation to induce DVT, and orally administered with DHK (3.20 mg/kg/d), warfarin (2.00 mg/kg/d), or vehicle for 7 days. The involved inferior vena cava and thrombi were collected and measured in size. The tissue specimens were performed for routine histopathologic evaluation and immunohistochemical staining with tissue factor and matrix metalloproteinases-9. Blood samples were collected for detecting coagulation function, blood cell count, and the levels of interleukin-6 and tumor necrosis factor-α. RESULTS: The treatment of DHK markedly reduced the size of thrombi by 49.26%, and the vein wall thickness by 47.86%. The recanalization rate was significant higher in the DHK-treated group than the vehicle-treated group (26.34 ± 6.53% versus 15.91 ± 3.93%, P < 0.01). Comparing to vehicle control, DHK significantly reduced neutrophils (P < 0.05) and lymphocytes (P < 0.05), serum tumor necrosis factor-α level (4.90 ± 1.14 pg/mL versus 6.60 ± 1.62 pg/mL, P < 0.01), and the expression of matrix metalloproteinases-9 and tissue factor (P < 0.05) in thrombi. CONCLUSIONS: DHK effectively prevented DVT through anti-inflammatory action in rats.

Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats.

AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.

Cloud computing-based TagSNP selection algorithm for human genome data.

Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.

Ocular pharmacokinetics of naringenin eye drops following topical administration to rabbits.

PURPOSE: To investigate the ocular pharmacokinetics of 1% naringenin eye drops following topical administration to rabbits. METHODS: One drop (50 µL) of 1% naringenin eye drops was instilled into both eyes of each rabbit. The animals were sacrificed at predetermined intervals after dosing, and ocular tissues and plasma were then collected. Concentrations of naringenin were analyzed using specific electrospray ionization liquid chromatography-tandem mass spectrometry method, which is proved to be sensitive, specific, precise, and suitable for determination of naringenin in ocular tissues and plasma of rabbits. RESULTS: Ocular exposure to naringenin, based on AUC(0-t), was highest in cornea, followed by aqueous humor, retina, and vitreous body. The Cmax of naringenin in cornea, aqueous humor, vitreous body, and retina were 67945.30 ± 4109.34 ng/g, 1325.69 ± 239.34, 160.52 ± 38.78 ng/mL, and 1927.08 ± 660.77 ng/g at 0.083, 0.75, 0.083, and 0.083 h after topical administration, respectively. The half-lives for these tissues were 9.37, 0.65, 1.17, and 4.62 h, respectively. There was no significant difference between free naringenin and total naringenin in plasma based on Cmax and Tmax. Cmax of total naringenin in plasma at 0.083 h was 35.12 ± 0.54 ng/mL. CONCLUSIONS: Measurable concentrations of naringenin were achieved in ocular tissues after topical application in rabbits. Topical instillation of naringenin may be an effective approach in the treatment of posterior section diseases.