Analysis of the hemostatic effect of preset wrapping technique for type A aortic dissection with abnormal coagulation.

Background: There are many techniques to reduce anastomotic bleeding for the total arch replacement, but hemostasis is sometimes difficult to achieve after surgery for acute dissection, especially in patients with abnormal coagulation (AC). This study aimed to investigate the hemostatic effect and early efficacy of a pre-set bovine pericardium wrapper in the right heart system shunt for total arch replacement in patients with type A aortic dissection (TAAD) and preoperative AC. Methods: A retrospective analysis was conducted on 85 patients with TAAD and AC who underwent total arch replacement between January 2018 and December 2022. The patients were divided into two groups: the preset pericardium group (n=30) and the control group (n=55). Results: There were no significant differences between the two groups in terms of Bentall surgery (ascending aorta replacement with an aortic valve artificial vessel) and cardiac arrest time. However, compared to the control group, the preset pericardium group exhibited a shorter duration of cardiopulmonary bypass (CPB) and operation (P<0.001). Additionally, the preset pericardium group required fewer transfusions of blood products and hemostatic drugs (P<0.05). Moreover, the preset pericardium group had lower 24-hour postoperative mediastinal drainage volume (P<0.001), a lower proportion of bedside hemofiltration (P=0.039), and a shorter duration of mechanical ventilation and stay in the intensive care unit (P=0.014). Although the preset pericardium group showed reductions in in-hospital mortality, re-exploration for bleeding, and neurologic dysfunction, these differences were not statistically significant compared to the control group. Conclusions: This study represents the first investigation into the application of the preset wrapping technique in total arch replacement for TAAD with AC. The results demonstrate that this method can reduce the duration of CPB and operation, decrease postoperative bleeding, and minimize the need for blood transfusion and hemostatic drugs. Consequently, this technique may contribute to early postoperative recovery.

Ameliorative effect of dandelion (Taraxacum officinale) peptides on benzo(a)pyrene-induced oxidative stress and inflammation in human umbilical vein endothelial cells.

Dandelion (Taraxacum officinale) is widely consumed as a health food and a traditional medicine. However, the protective effect of dandelion bio-active peptides (DPs) against polycyclic aromatic hydrocarbon-induced blood vessel inflammation and oxidative damage is not well documented. In the current study, four novel DPs were isolated using an activity tracking method. The protective activity of the DPs against benzo(a)pyrene (Bap)-induced human umbilical vein endothelial cell (HUVEC) damage was explored. The results indicated that DP-2 [cycle-(Thr-His-Ala-Trp)] effectively inhibited Bap-induced reactive oxygen species (ROS) and malondialdehyde (MDA) overproduction and reinforced antioxidant enzyme activity while inhibiting the production of inflammatory factors in HUVECs. Moreover, DP-2 increased NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and nuclear factor E2-releated factor 2 expression levels by activating the PI3K/Akt signaling pathway. In addition, DP-2 attenuated Bap-induced HUVEC apoptosis via the Bcl-2/Bax/cytochrome c apoptotic pathway. These results suggest that DP-2 is a promising compound for protecting HUVECs from Bap-induced inflammatory and oxidative damage.

Comparative viromes of Culicoides and mosquitoes reveal their consistency and diversity in viral profiles.

The genus Culicoides includes biting midges, some of which are vectors for viruses that cause diseases in humans and animals. Knowledge of the roles of Culicoides in viral ecology is inadequate. We collected ~300 000 samples of Culicoides and mosquitoes in 15 representative regions within Yunnan, China. Using mosquitoes as reference vectors, we designed a comparative virome strategy to study the viral composition, diversity, hosts and spatiotemporal distribution of Culicoides. A map of viromes in Culicoides and mosquitoes in Yunan province, China, was constructed. At the same locations, Culicoides and mosquitoes usually share a similar viral diversity. At least 10 important pathogenic viruses were detected from Culicoides. Many novel viruses were discovered, including 21 segmented viruses of Flaviviridae, 180 viruses of Monjiviricetes and 130 viruses of Bunyavirales. The findings demonstrate that Culicoides is an important part of viral ecology and should be studied and monitored for potentially emerging viruses.

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV.

Background: The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. Methods: We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Results: Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Conclusions: Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence Summary: Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

Parkin ubiquitinates GATA4 and attenuates the GATA4/GAS1 signaling and detrimental effects on diabetic nephropathy.

Renal tubular injury contributes to the progression of diabetic nephropathy (DN). This study explored the role and mechanisms of E3-ubiquitin ligase Parkin in the renal tubular injury of DN. We found that Parkin expression gradually decreased and was inversely associated with IL-6, TGF-ß1, and GATA4 expression in the kidney during the progression of DN. Parkin over-expression (OE) reduced inflammation, fibrosis, premature senescence of renal tubular epithelial cells (RTECs), and improved renal function while Parkin knockout (KO) had opposite effects in DN mice. Parkin-OE decreased GATA4 protein, but not its mRNA transcripts in the kidney of DN mice and high glucose (HG)-treated RTECs. Immunoprecipitation indicated that Parkin directly interacted with GATA4 in DN kidney. Parkin-OE enhanced GATA4 ubiquitination. Furthermore, Parkin-KO upregulated growth arrest-specific gene 1 (GAS1) expression in renal tubular tissues of DN mice and GATA4-OE enhanced the HG-upregulated GAS1 expression in RTECs. Conversely, GAS1-OE mitigated the effect of Parkin-OE on HG-induced P21, IL-6, and TGF-ß1 expression in RTECs. These results indicate that Parkin inhibits the progression of DN by promoting GATA4 ubiquitination and downregulating the GATA4/GAS1 signaling to inhibit premature senescence, inflammation, and fibrosis in DN mice. Thus, these findings uncover new mechanisms underlying the action of Parkin during the process of DN.

Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China.

An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

Crocin Alleviates Myocardial Ischemia/Reperfusion-Induced Endoplasmic Reticulum Stress via Regulation of miR-34a/Sirt1/Nrf2 Pathway.

Endoplasmic reticulum (ER) stress is associated with ischemia/reperfusion (I/R)-induced cardiomyocyte apoptosis. Crocin could protect myocardial cells against I/R injury and suppress ER stress. This study aimed to explore the molecular mechanism of crocin related to ER stress in myocardial I/R injury. We found crocin alleviated I/R-induced cardiomyocyte apoptosis both in I/R-induced primary cardiomyocytes and in mouse models. The expression of Bax, active caspase 3, glucose-regulated protein of 78 kDa (GRP78), and C/EBP homologous protein (CHOP) induced by I/R injury was reduced, whereas Bcl-2 expression was enhanced by crocin, the effect of which was abrogated by ER stress activator thapsigargin treatment. Crocin decreased miR-34a expression, whereas it increased Sirt1, Nrf2, and HO-1 levels, in I/R-induced cardiomyocytes. miR-34a overexpression reduced the expression of Sirt1, Nrf2, and HO-1; in contrast, the suppression of miR-34a upregulated their expression. Sirt1 blocker nicotinamide and Nrf2 siRNA restrained the levels of GRP78, CHOP, Bax, and active caspase 3. The levels of apoptosis- and ER stress-related proteins, and the expression of miR-34a, Sirt1, Nrf2, and HO-1 in I/R-induced mouse models were consistent with those in vitro. In addition, I/R-induced left ventricular dysfunction and infarct were attenuated by crocin in mice. In conclusion, crocin attenuates I/R-induced cardiomyocyte apoptosis via suppressing ER stress, which is regulated by the miR-34a/Sirt1/Nrf2 pathway.

Concomitant surgical atrial fibrillation ablation is safe and efficacious in patients undergoing double valve replacement - A cohort study.

BACKGROUND: Current European Society of Cardiology Guidelines recommend concomitant atrial fibrillation (AF) ablation for all symptomatic patients undergoing other cardiac surgeries, but the safety and potential benefits of concomitant atrial fibrillation (AF) ablation at the time of double valve replacement (DVR: aortic and mitral valve replacement) remains unexamined. MATERIALS AND METHODS: We conducted a retrospective review of 238 patients with AF who underwent DVR with or without concomitant surgical ablation (Ablation group, n = 113; Non-ablation group, n = 125) at a single institute from April 2006 to September 2011. RESULTS: There were no significant group differences in early postoperative mortality and morbidity, late survival, and freedom from major cardiac and cerebrovascular events (MACCEs). However, the Ablation group exhibited higher rates of sinus rhythm restoration at discharge (86.7% vs. 5.6%, P < 0.01) and at last follow-up (71.2% vs. 8.5%, P < 0.01). Follow-up echocardiography demonstrated smaller left atrial dimension and higher ejection fraction in the Ablation group (both P < 0.01). CONCLUSION: Concomitant surgical ablation for AF did not increase perioperative mortality or morbidity in patients undergoing DVR, but significantly increased sinus rhythm restoration, improved heart function, and decreased oral anticoagulation requirements.

The effect of antegrade pulmonary blood flow following a late bidirectional Glenn procedure.

OBJECTIVES: The effect of antegrade pulmonary blood flow (APBF) has never been studied in the bidirectional Glenn (BDG) procedure performed late. METHODS: Records of 112 consecutive patients who had a BDG procedure during a 10-year period were reviewed retrospectively. The patients were divided into 2 groups based on whether APBF occurred following the BDG procedure (APBF group, n = 81) or not (non-APBF group, n = 31). The median age at the BDG procedure was 6.16 ± 3.93 years in the APBF group and 6.12 ± 4.40 years in the non-APBF group. RESULTS: Demographics and pre- and intraoperative variables were comparable for both groups. Follow-up data were obtained for patients at the BDG stage and for those who had undergone the Fontan completion. Both oxygen saturation levels (81.72 ± 1.976% vs 78.32 ± 2.344%, P < 0.01) and pulmonary pressure (13.59 ± 1.376 mmHg vs 12.90 ± 0.978 mmHg, P = 0.012) were higher in the APBF group immediately after the BDG procedure. Both the duration of chest tube drainage and the total length of stay were longer in the APBF group. The pre-Glenn measurements showed a mean McGoon ratio of 1.68 ± 0.114 in the APBF group and 1.67 ± 0.098 in the non-APBF group (P = 0.474). The McGoon ratios measured before the Fontan procedure were also comparable (1.669 ± 0.726 vs 1.685 ± 0.669, P = 0.576). At the pre-Fontan measurement, there was no significant difference in mean pulmonary artery pressures between the groups (13.72 ± 1.368 vs 13.50 ± 1.265, P = 0.653). Fifty-nine patients underwent the Fontan completion (43 from the APBF group and 16 from the non-APBF group) procedure with a median of 1.2 (APBF group) and 1.4 (non-APBF group) years after the BDG procedure. No significant differences between groups were observed in arterial oxygen saturation levels, incidence of systemic atrioventricular valve regurgitation or ventricular dysfunction in survivors at the last follow-up visit. CONCLUSIONS: The BDG procedure can be safely performed at a relatively older age (∼6 years). APBF increases oxygen saturation but also prolongs pleural effusion and hospital stay. Medium-term outcomes and the Fontan completion rate in the APBF and the non-APBF groups are comparable. Further large studies and long-term follow-up are needed to clarify the effect of APBF in patients who have the late BDG.

An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations.

MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug.

Bilateral versus unilateral antegrade cerebral perfusion in total arch replacement for type A aortic dissection.

BACKGROUND: Antegrade cerebral perfusion (ACP) is the most widely used cerebral protection strategy for complex aortic repair and includes unilateral (u-ACP) and bilateral (b-ACP) techniques. The superiority of b-ACP over u-ACP has been the subject of much debate. Focusing on type A aortic dissection requiring total arch replacement, we investigated the clinical effects of b-ACP versus u-ACP. METHODS: Between September 2006 and August 2014, 203 patients presenting with type A aortic dissection (median age, 51.0 ± 13 years; range, 17-72 years; 128 males) underwent total aortic arch replacement with hypothermic circulatory arrest. ACP was used in all patients, including u-ACP in 82 (40.3%) and b-ACP in 121 (59.7%). RESULTS: There was no significant difference between the u-ACP and b-ACP groups in terms of cardiopulmonary bypass (CPB) time, cross-clamp time, or circulatory arrest time. Overall 30-day mortality was comparable in the 2 groups (11.6% for b-ACP vs 20.7% for u-ACP; P = .075). The prevalence of postoperative permanent neurologic dysfunction (PND) was comparable as well (8.4% vs 16.9%; P = .091). Mean ventilation time was lower in the b-ACP group (95.5 ± 45.25 hours vs 147.0 ± 82 hours; P < .001). Mean lengths of stay in the intensive care unit and the hospital overall were comparable in the 2 groups (intensive care unit: 16 ± 17.75 days vs 17 ± 11.5 days, P = .454; hospital: 26.5 ± 20.6 days vs 24.8 ± 10.3 days, P = .434). The P values from logistic regression models indicated that in the 2 groups combined, CPB time and circulatory arrest time were independent risk factors for both mortality and PND. CONCLUSIONS: In this, the first published study focusing on the efficacy of u-ACP and b-ACP in total arch replacement for type A aortic dissection, the b-ACP group did not demonstrate significantly lower 30-day mortality or PND rate compared with the u-ACP group. Future large-sample studies are warranted to thoroughly examine this critical issue.

Inferring Alcoholism SNPs and Regulatory Chemical Compounds Based on Ensemble Bayesian Network.

AIM AND OBJECTIVE: The disturbance of consciousness is one of the most common symptoms of those have alcoholism and may cause disability and mortality. Previous studies indicated that several single nucleotide polymorphisms (SNP) increase the susceptibility of alcoholism. In this study, we utilized the Ensemble Bayesian Network (EBN) method to identify causal SNPs of alcoholism based on the verified GAW14 data. MATERIALS AND METHODS: We built a Bayesian network combining random process and greedy search by using Genetic Analysis Workshop 14 (GAW14) dataset to establish EBN of SNPs. Then we predicted the association between SNPs and alcoholism by determining Bayes' prior probability. RESULTS AND CONCLUSION: Thirteen out of eighteen SNPs directly connected with alcoholism were found concordance with potential risk regions of alcoholism in OMIM database. As many SNPs were found contributing to alteration on gene expression, known as expression quantitative trait loci (eQTLs), we further sought to identify chemical compounds acting as regulators of alcoholism genes captured by causal SNPs. Chloroprene and valproic acid were identified as the expression regulators for genes C11orf66 and SALL3 which were captured by alcoholism SNPs, respectively.

[Protective effects of high-dose ulinastatin on vital organs in patients receiving total arch replacement for type A aortic dissection].

OBJECTIVE: To investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection. METHODS: Between September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared. RESULTS: s The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05). CONCLUSION: High-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.

Inhibition of acid sensing ion channel by ligustrazine on angina model in rat.

Ligustrazine, a compound extracted from roots of Ligusticum chuanxiong, is widely used in Chinese traditional medicine to treat cardiac and cerebrovascular diseases and pain, including angina. The mechanism(s) of ligustrazine's effect to reduce angina is not clear. Angina is mediated by cardiac afferent sensory neurons. These neurons display a large acid-evoked depolarizing sodium current that can initiate action potentials in response to acidification that accompanies myocardial ischemia. Acid-sensing ion channels (ASICs) mediate this current. Here we tested the hypothesis that ligustrazine reduces ischemia-induced cardiac dysfunction and acid-evoked pain by an action to inhibit ASIC-mediated current. The effects of ligustrazine to attenuate ischemia-induced ST-segment depression, T wave changes, and myocardial infarct size in hearts of anesthetized rats were determined. Effects of ligustrazine on currents mediated by ASICs expressed in cultured Chinese hamster ovary cells, and effects of the drug on acid-induced nociceptive behavior and acid-induced currents in isolated dorsal root ganglions cells were measured. Ligustrazine significantly attenuated acid-induced ASIC currents, reduced cardiac ischemia-induced electrical dysfunction and infarct size, and decreased the nociceptive response to injection of acid into the paw of the rat hindlimb. The ASIC channel inhibitor A-317567 similarly reduced electrical dysfunction, infarct size, and nociceptive behavior in the rat. Inhibition of ASICs by ligustrazine may explain at least in part the beneficial effects of the drug that are observed in patients with ischemic heart disease and angina.

Inhibitory effects of resveratrol on foam cell formation are mediated through monocyte chemotactic protein-1 and lipid metabolism-related proteins.

Resveratrol has been shown to exert anti-atherosclerotic effects. 5' AMP-activated protein kinase (AMPK) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation, which is considered as the initiation of atherosclerosis. Thus, in this study, we investigated whether resveratrol inhibits foam cell formation by regulating lipid accumulation and inflammation. For this purpose, THP-1 cells were treated with 100 nM phorbol 12-myristate 13-acetate (PMA) to induce their differentiation into macrophages. The macrophages were then pre-treated with 2.5 µM resveratrol and subsequently with serum-free (SF) medium alone or SF medium containing lipopolysaccharide (LPS; 100 ng/ml) and oxidized low-density lipoprotein (ox-LDL; 50 µg/ml) for 24 h to detect foam cell formation. To detect the expression of lipid accumulation-related proteins, the macrophages were treated with resveratrol. For the detection MCP-1 expression, the macrophages were treated with LPS and resveratrol, or with resveratrol alone. We incubated the THP-1-derived macrophages in resveratrol (2.5 µM) for 6 h in the presence or absence of 30 µM compound C for 4 h to detect the influence of compound C on the effects of resveratrol. The foam cells were examined using Red O staining. Gene expression levels were determined by qRT-PCR, western blot analysis and ELISA; lipid analysis was carried out by high-performance liquid chromatography (HPLC). The results revealed that resveratrol effectively suppressed foam cell formation induced by LPS. Resveratrol also suppressed lipid accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ and PPARα, but had no effect on the expression of PPARß/δ. Resveratrol also upregulated the expression of AMPK and Silent information regulator T1 (SIRT1). However, the effects of resveratrol on SIRT1, PPARγ and PPARα expression and lipid accumulation were reversed when the cells were pre-treated with compound C. Resveratrol downregulated the mRNA expression of MCP-1 in a dose-dependent manner and LPS upregulate its expression in a time-dependent manner. MCP-1 expression induced by LPS was inhibited by resveratrol at both the transcriptional and translational level. These data suggest that resveratrol inhibits foam cell formation by regulating the expression of MCP-1 and activating the AMPK-SIRT1-PPAR signaling pathway; thus, resveratrol may be a novel therapeutic agent for atherosclerosis.

Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury.

BACKGROUND: Resveratrol has been shown to attenuate reactive oxygen species formation and protect against ischemia-reperfusion (I/R) injury. However, the effects of resveratrol against subacute intestinal I/R injury are not clearly elucidated. Therefore, this study was designed to investigate the effects and possible protective mechanisms of resveratrol on subacute intestinal I/R injury in mice. METHODS: BALB/c mice were subjected to 1 h ischemia by occluding the superior mesenteric artery and 24 h reperfusion. Histologic injury; myeloperoxidase, superoxide dismutase, and glutathione peroxidase activity; malondialdehyde level; inducible nitric oxide synthase (iNOS), Ac-NF-κBp65, and sirtuin 1 (SIRT1) expression; NF-κB translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors. RESULTS: Resveratrol significantly ameliorated subacute intestinal I/R injury accompanied with the decrease of NO production as well as iNOS expression. In addition, resveratrol obviously upregulated the expression of SIRT1 and inhibited the activity of NF-κB. After application of iNOS inhibitor S-methylisothiourea and NF-κB inhibitor pyrrolidine dithiocarbamate, the protective effect of resveratrol was significantly augmented by attenuating iNOS and NO production, indicating that resveratrol exerted its protective effect on intestinal I/R injury via NF-κB-mediated iNOS pathway. Furthermore, the protective effect of resveratrol was correlated with SIRT1, because application of SIRT1 inhibitor nicotinamide strikingly weakened the protective effect of resveratrol. CONCLUSIONS: Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-κB pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy.

Protective effects of osthole against myocardial ischemia/reperfusion injury in rats.

Osthole, a bioactive simple coumarin derivative extracted from a number of medicinal plants, such as Cnidium monnieri and Angelica pubescens, has been shown to exert a variety of pharmacological activities and is considered to have potential therapeutic applications. In this study, we investigated the protective effects of osthole against myocardial ischemia/reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were randomly assigned to 1 of 5 groups: the sham-oeprated control group (control), the vehicle group (vehicle), and 3 treatment groups, which were treated with osthole at the concentration of 1, 10 or 50 mg/kg (intraperitoneally), respectively, upon the initiation of myocardial ischemia. Treatment with osthole suppressed the formation of lipid peroxidation products, enhanced the capacities of antioxidant enzymes and inhibited the expression of inflammatory cytokines following myocardial I/R injury. Moreover, treatment with osthole reduced high-mobility group box protein 1 (HMGB1) and phosphorylated nuclear factor (NF)-κB expression in ischemic myocardial tissue. These results demonstrate the protective effects of osthole against myocardial I/R injury in rats and suggest that these effects may be associated with its antioxidant and anti-inflammatory activities.

Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice.

Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.