Electrical Stimulation Induces Activation of Mitochondrial Apoptotic Pathway and Down-Regulates Heat Shock Proteins in Pork: An Innovative Strategy for Enhancing the Ripening Process and Quality of Dry-Cured Loin Ham.

A fundamental regulatory framework to elucidate the role of electrical stimulation (ES) in reducing long production cycles, enhancing protein utilization, and boosting product quality of dry-cured ham is essential. However, how mitochondria and enzymes in meat fibers are altered by ES during post-processing, curing, and fermentation procedures remains elusive. This study sought to explore the impact of ES on the regulation of heat shock proteins (HSP27, HSP70), apoptotic pathways, and subsequent influences on dry-cured pork loin quality. The gathered data validated the hypothesis that ES notably escalates mitochondrial oxidative stress and accelerates mitochondrial degradation along the ripening process. The proapoptotic response in ES-treated samples was increased by 120.7%, with a cellular apoptosis rate 5-fold higher than that in control samples. This mitochondrial degradation is marked by increased ratios of Bax/Bcl-2 protein along the time course, indicating that apoptosis could contribute to the dry-cured ham processing. ES was shown to further down-regulate HSP27 and HSP70, establishing a direct correlation with the activation of mitochondrial apoptosis pathways, accompanied by dry-cured ham quality improvements. The findings show that ES plays a crucial role in facilitating the ripening of dry-cured ham by inducing mitochondrial apoptosis to reduce HSP expression. This knowledge not only explains the fundamental mechanisms behind myofibril degradation in dry-cured ham production but also offers a promising approach to enhance quality and consistency.

Rational Design of Activatable Lanthanide NIR-IIb Emissive Nanoprobe for In Situ Specific Imaging of HOCl In Vivo.

Hypochlorous acid (HOCl), as an indispensable signaling molecule in organisms, is one of the key members of reactive oxygen species (ROS). However, in vivo, real-time dynamic near-infrared fluorescence imaging of HOCl levels in the 1400-1700 nm sub-window (NIR-IIb) remains a major challenge due to the lack of suitable detection methods. Herein, a general design of HOCl-responsive NIR-IIb fluorescence nanoprobe is proposed by integrating NaLuF4Yb/Er@NaLuF4 downshift nanoparticles (DSNPs) and HOCl recognition/NIR-IIb emissive modulation unit of M2-xS (M = Cu, Co, Pb) nanodots for real-time monitoring of HOCl levels. The fluorescence modulation unit of M2-xS nanodots presents remarkably enhanced absorption than Yb sensitizer at 980 nm and greatly inhibits the NIR-IIb fluorescence emission via competitive absorption mechanism. While, the M2-xS nanodots are easily degraded after triggering by HOCl, resulting in HOCl responsive turn-on (≈ten folds) NIR-IIb emission at 1532 nm. More importantly, in vivo highly precise and specific monitoring of inflammatory with abnormal HOCl expression is successfully achieved. Thus, the explored competitive absorption mediated quenching-activation mechanism provides a new general strategy of designing HOCl-responsive NIR-IIb fluorescence nanoprobe for highly specific and sensitive HOCl detection.

Perilla seed oil high internal phase emulsion improve the gel properties of myofibrillar protein.

The effects of perilla seed oil high internal phase emulsions stabilized by pea protein (PP-PSO HIPEs) on the gel properties and conformation of myofibrillar protein (MP) gels were investigated. The results showed that the PP-PSO HIPEs with 4.0 % (w/v) PP formed stable HIPEs with low droplet size and good viscoelasticity. The addition of PP-PSO HIPEs (5.0 % - 15.0 %) could significantly improve the MP gel properties (P < 0.05), while the addition of 10.0 % PP-PSO HIPEs showed the highest gel strength and water holding capacity. Otherwise, the MP gels with 10.0 % PP-PSO HIPEs showed higher proportions of immobile water (PT22) and lower proportion of free water (PT23), and the Raman spectra suggested that the content of α-helix decreased, while the content of ß-sheet increased (P < 0.05), thus facilitating the formation of better gel properties. Therefore, the addition of PP-PSO HIPEs is a potential alternative for developing fat-reduced meat products.

An Activated Structure Transformable Ratiometric Photoacoustic Nanoprobe for Real-Time Dynamic Monitoring of H2S In Vivo.

H2S has emerged as a promising biomarker for many diseases such as colon cancer and metformin-induced hepatotoxicity. Real-time monitoring of H2S levels in vivo is significant for early accurate diagnosis of these diseases. Herein, a new accurate and reliable nanoprobe (Au NRs@Ag) was designed for real-time dynamic ratiometric photoacoustic (PA) imaging of H2S in vivo based on the endogenous H2S-triggered local surface plasmon resonance (LSPR) red-shift. The Au NRs@Ag nanoprobe can be readily converted into Au NRs@Ag2S via the endogenous H2S-activated in situ sulfurative reaction, subsequently leading to a significant red-shift of the LSPR wavelength from 808 to 980 nm and enabling accurate ratiometric PA (PA980/PA808) imaging of H2S. Moreover, dynamic ratiometric PA imaging of metformin-induced hepatotoxicity was also successfully achieved by the designed PA imaging strategy. These findings provide the possibility of designing a new ratiometric PA imaging strategy for dynamic in situ monitoring of H2S-related diseases.

Structural and functional changes on polyhydroxy alcohol-mediated curing pork myofibrillar protein: Experimental and molecular simulation investigations.

This study aimed to investigate the structural and functional changes in polyhydroxy alcohol-mediated curing on pork myofibrillar proteins (MP). The results obtained from total sulfhydryl groups, surface hydrophobicity, fluorescence and Raman spectroscopies, and solubility demonstrated that the polyhydroxy alcohols (especially xylitol) significantly modified the MP tertiary structure, making this structure more hydrophobic and tighter. However, no significant differences were detected in the secondary structure. Furthermore, the thermodynamic analysis revealed that polyhydroxy alcohols could develop an amphiphilic interfacial layer on the MP surface, significantly increasing the denaturation temperature and enthalpy of denaturation (P < 0.05). On the other hand, the molecular docking and dynamics simulations showed that polyhydroxy alcohols interact with actin mainly through hydrogen bonds and van der Waals forces. Therefore, this could help reduce the effect of high-content salt ions on MP denaturation and improve the cured meat quality.

Simulation Study of Xylitol-Mediated Effect on NaCl Diffusion Behavior in Cured Pork Tenderloin.

Polyhydroxy alcohol-mediated curing has great potential for producing low-salt cured meat products. This study investigated the mass transfer kinetics and the one-way diffusion simulation of sodium chloride (NaCl) during the curing process. Furthermore, Fick's second law determined the NaCl diffusion coefficient (De) of xylitol-mediated cured pork tenderloin. The results demonstrated that adding xylitol could reduce the De of NaCl. The De of NaCl, calculated using the one-way model, was 1.29 × 10-9 m2·s-1, 1.22 × 10-9 m2·s-1, 1.2 × 10-9 m2·s-1, and 1.15 × 10-9 m2·s-1 when the amount of xylitol added was 0%, 4%, 8%, and 12% (w/w), respectively. This result agrees with the predicted values from the power function time-varying model. Moreover, a three-dimensional simulating model of mass transfers constructed using COMSOL Multiphysics was developed to evaluate the NaCl diffusion in pork tenderloin during the curing process. This model has high accuracy and can be used to describe the diffusion of NaCl in curing. Overall, this study provided a foundation for NaCl diffusion and distribution during the curing process.

Complete Mitochondrial Genome of Piophila casei (Diptera: Piophilidae): Genome Description and Phylogenetic Implications.

Piophila casei is a flesh-feeding Diptera insect that adversely affects foodstuffs, such as dry-cured ham and cheese, and decaying human and animal carcasses. However, the unknown mitochondrial genome of P. casei can provide information on its genetic structure and phylogenetic position, which is of great significance to the research on its prevention and control. Therefore, we sequenced, annotated, and analyzed the previously unknown complete mitochondrial genome of P. casei. The complete mt genome of P. casei is a typical circular DNA, 15,785 bp in length, with a high A + T content of 76.6%. It contains 13 protein-coding genes (PCG), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 1 control region. Phylogenetic analysis of 25 Diptera species was conducted using Bayesian and maximum likelihood methods, and their divergence times were inferred. The comparison of the mt genomes from two morphologically similar insects P. casei and Piophila megastigmata indicates a divergence time of 7.28 MYA between these species. The study provides a reference for understanding the forensic medicine, taxonomy, and genetics of P. casei.

NIR-II Light-Activated Gold Nanorods for Synergistic Thermodynamic and Photothermal Therapy of Tumor.

There are tricky challenges in tumor therapy due to the hypoxic tumor microenvironment, inevitably inhibiting the treatment efficacy of the traditional photodynamic therapy (PDT), radiation therapy (RT), and sonodynamic therapy (SDT). Herein, to overcome tumor hypoxia limitation, we constructed a near-infrared II (NIR-II) light-triggered thermodynamic therapy (TDT) nanoplatform of Au@mSiO2-AIPH@PCM/PEG (ASAPP) by integrating the Au nanorods (Au NRs) and thermally activated alkyl free radical-releasing molecules (AIPH). Au NRs@mSiO2 was used as a photothermally responsive material and AIPH carrier, and the hot-melt phase-change material (PCM) was used as a capping agent to prevent leakage of AIPH during blood circulation. Upon NIR-II light irradiation, heat-triggered free radical release from AIPH was successfully achieved for killing cancer cells in vitro and in vivo without oxygen dependence, leading to synergistically enhanced antitumor therapy.

NIR-II Responsive Upconversion Nanoprobe with Simultaneously Enhanced Single-Band Red Luminescence and Phase/Size Control for Bioimaging and Photodynamic Therapy.

Lanthanide based upconversion (UC) nanoprobes have emerged as promising agents for biological applications. Extending the excitation light to the second near-infrared (NIR-II), instead of the traditional 980/808 nm light, and realizing NIR-II responsive single-band red UC emission is highly demanded for bioimaging application, which has not yet been explored. Here, a new type of NIR-II (1532 nm) light responsive UC nanoparticles (UCNPs) with enhanced single-band red UC emission and controllable phase and size is designed by introducing Er3+ as sensitizer and utilizing Mn2+ as energy manipulator. Through tuning the content of Mn2+ in NaLnF4 :Er/Mn, the crystal phase, size, and emitting color are readily controlled, and the red-to-green (R/G) ratio is significantly increased from ≈20 to ≈300, leading to NIR-II responsive single band red emission via efficient energy transfer between Er3+ and Mn2+ . In addition, the single band red emitting intensity can be further improved by coating shell to avoid the surface quenching effect. More importantly, NIR-II light activated red UC bioimaging and photodynamic therapy through loading photosensitizer of zinc phthalocyanine are successfully achieved for the first time. These findings provide a new strategy of designing NIR-II light responsive single-band red emissive UCNPs for biomedical applications.

Mechanism of polyhydroxy alcohol-mediated curing on moisture migration of minced pork tenderloin: On the basis of molecular docking.

This study investigated the mechanism of glycerol, xylitol, and sorbitol-mediated curing of cured minced pork tenderloin. The use of polyhydroxy alcohol during mediated curing significantly reduced the salt content (p < 0.01) and water activity (aw) of the cured pork tenderloin. Low-field nuclear magnetic resonance (LFNMR) revealed that 1 % glycerol, 1 % xylitol, 1 % sorbitol, and 10 % glycerol-mediated curing decreased water mobility, and improved water holding capacity (WHC), and produced uniform dense microstructures. Raman spectroscopy and molecular docking indicated that polyhydroxy alcohols formed hydrogen bonds with myosin, as well as hydrogen bonds with free water molecules to convert free water into bound water to reduce aw, and altered the hydrophobic environment of myosin surface to reduce structural damage caused by high salt content. In conclusion, using polyhydroxy alcohol to mediate curing can effectively reduce the salt content of cured meat and provide a theoretical basis for its application in the cured meat industry.

Recyclable Endogenous H2 S Activation of Self-Assembled Nanoprobe with Controllable Biodegradation for Synergistically Enhanced Colon Cancer-Specific Therapy.

Excessive production of hydrogen sulfide (H2 S) plays a crucial role in the progress of colon cancer. Construction of tumor-specific H2 S-activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2 S triggered Co-doped polyoxometalate (POM-Co) cluster with self-adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2 S/glutathione (GSH) is designed for synergistic enhanced tumor-specific photothermal and chemodynamic therapy. The designed POM-Co nanocluster holds H2 S responsive "turn-on" photothermal property in colon cancer via self-assembling to form large-sized POM-CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM-CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)-catalyzed •OH production and Russell mechanism-enabled 1 O2 generation with GSH consumption, respectively. More importantly, the degraded POM-CoS is reactivated by endogenous H2 S for recyclable and sustainable consumption of H2 S and GSH, resulting in tumor-specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment-driven nanoprobes with controllable biodegradation for precise and sustainable anti-tumor therapy.

A H2S-Triggered Dual-Modal Second Near-Infrared/Photoacoustic Intelligent Nanoprobe for Highly Specific Imaging of Colorectal Cancer.

An endogenous H2S-triggered intelligent optical nanoprobe combining second near-infrared (NIR-II) fluorescence with photoacoustic (PA) imaging can provide more comprehensive information to further improve the sensitivity and reliability of diagnosis for colorectal tumor, which is rarely explored. Herein, an endogenous H2S-triggered SiO2@Ag nanoprobe was designed for in situ dual-modal NIR-II/PA imaging of colorectal cancer. The designed dual-modal nanoprobe can be converted to SiO2@Ag2S after in situ biosynthesis via a sulfuration reaction with the over-expressed endogenous H2S in the colorectal tumor. More importantly, the designed SiO2@Ag nanoprobe exhibits high sensitivity and specificity for diagnosing colorectal cancer in vivo via dual-modal NIR-II/PA imaging. These results provide a new NIR-II/PA dual-modal imaging strategy for noninvasive intelligent detection of colorectal cancer.

Endogenous H2S-Activated Orthogonal Second Near-Infrared Emissive Nanoprobe for In Situ Ratiometric Fluorescence Imaging of Metformin-Induced Liver Injury.

Metformin as a hypoglycemic drug for antidiabetic treatment has emerged as a multipotential drug for many disease treatments such as cognitive disorders, cancers, promoting weight loss. However, overdose uptake may upregulate the hepatic H2S level, subsequently leading to serious liver injury and toxicity. Therefore, developing intelligent second near-infrared (NIR-II) emitting nanoprobes by using endogenous H2S as a smart trigger for noninvasive highly specific in situ monitoring of the metformin-induced hepatotoxicity is highly desirable, which is rarely explored. Herein, an endogenous H2S activated orthogonal NIR-II emitting myrica rubra-like nanoprobe based on NaYF4:Gd/Yb/Er@NaYF4:Yb@SiO2 coated with Ag nanodots was explored for highly specific in vivo ratiometrically monitoring of hepatotoxicity. The designed nanoprobes were mainly uptaken by the liver and subsequently converted to NaYF4:Gd/Yb/Er@NaYF4:Yb@SiO2@Ag2S via in situ sulfuration reaction triggered by the overexpressed endogenous H2S in the injured liver tissues, finally leading to a turn-on orthogonal emission centered at 1053 nm (irradiation by 808 nm laser) and 1525 nm (irradiation by 980 nm laser). The designed nanoprobe presents a high detection limit down to 0.7 nM of H2S. More importantly, the in situ highly specific ratiometric imaging of the metformin-induced hepatotoxicity was successfully achieved by using the activatable orthogonal NIR-II emitting probe. Our results provide an NIR-II ratiometric fluorescence imaging strategy for highly sensitive/specific diagnosis of hepatotoxicity levels induced by metformin.

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.

Lipopolysaccharide impairs permeability of pulmonary microvascular endothelial cells via Connexin40.

The endotoxin lipopolysaccharide (LPS)-induced pulmonary endothelial barrier disruption is a key pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the molecular mechanisms underlying LPS-impaired permeability of pulmonary microvascular endothelial cells (PMVECs) are not fully understood. Gap junctions, particularly Connexin40 (Cx40), are necessary for the maintenance of normal vascular function. In this study, we for the first time investigated the role of Cx40 in LPS-impaired permeability of PMVECs and provided potential therapeutic approaches based on mechanistic findings of Cx40 regulation by LPS stimuli. Rat PMVECs were isolated, cultured and identified with cell morphology, specific markers, ultrastructural characteristics and functional tests. Western blot analysis demonstrated that Cx40 is the major connexin highly expressed in PMVECs. Furthermore, by inhibiting Cx40 in a time-dependent manner, LPS impaired gap junction function and induced permeability injury of PMVECs. The key role of Cx40 decline in mediating detrimental effects of LPS was further confirmed in rescue experiments through Cx40 overexpression. Mechanistically, LPS stress on PMVECs inhibited the protein kinase C (PKC) pathway, which may synergize with the inflammatory nuclear factor kappaB (NFκB) signaling activation in suppressing Cx40 expression level and phosphorylation. Moreover, through pharmacological PKC activation or NFκB inhibition, Cx40 activity in PMVECs could be restored, leading to maintained barrier function under LPS stress. Our findings uncover a previously unrecognized role of Cx40 and its regulatory mechanisms in impaired endothelial integrity under endotoxin and inflammation, shedding light on intervention approaches to improve pulmonary endothelial barrier function in ALI and ARDS.

[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.

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.