Hyperbaric Oxygen Attenuates Chronic Postsurgical Pain by Regulating the CD73/Adenosine/A1R Axis of the Spinal Cord in Rats.

Chronic postsurgical pain (CPSP) affects postoperative rehabilitation and quality of life in patients, but its mechanisms are still poorly understood. Hyperbaric oxygen (HBO) attenuates neuropathic pain in animal and human studies, but its efficacy for CPSP treatment and its underlying mechanism have not been elucidated. This study aimed to investigate the analgesic effect of HBO in a CPSP rat model and the role of spinal cord adenosine circulation in HBO-induced analgesia. A skin/muscle incision and retraction (SMIR) rat model was used to mimic CPSP, and HBO treatment (2.5 atmospheric absolute, 60 minutes) was administered once daily for 5 consecutive days beginning 3 days after surgery. The role of spinal cord adenosine circulation in HBO-induced analgesia was investigated using ß-methylene ADP (a CD73 inhibitor), 8-cyclopentyl-1,3-dipropylxanthine (an A1R antagonist), or an intrathecal injection of adenosine. The mechanical paw withdrawal threshold was determined at different timepoints before and after surgery. The spinal cord adenosine and adenosine triphosphate (ATP) contents were analyzed using high-performance liquid chromatography, and the spinal cord expression of adenosine-1 receptor (A1R), extracellular 5'-nucleotidase (CD73), and adenosine kinase (ADK) was examined by Western blotting and immunofluorescence staining. The results showed that the mechanical paw withdrawal threshold of the ipsilateral hind paw and the adenosine content decreased, and the spinal cord expression of A1R, CD73, and ADK and ATP content increased within 14 days after surgery. HBO treatment alleviated mechanical allodynia, reduced ATP content, and increased adenosine content by activating CD73 but downregulated the spinal cord expression of A1R, CD73, and ADK. Intrathecal adenosine alleviated mechanical allodynia after SMIR and downregulated the spinal cord expression of A1R and CD73, and intrathecal ß-methylene ADP or 8-cyclopentyl-1,3-dipropylxanthine attenuated the analgesic effect of HBO treatment on SMIR-induced CPSP. PERSPECTIVE: Spinal cord adenosine is involved in the occurrence and development of CPSP, and HBO treatment alleviates CPSP by regulating adenosine production/metabolism in the spinal cord. Thus, HBO may be employed for the treatment of CPSP with favorable efficacy.

Mechanisms of intestinal epithelial cell damage by Clostridiumperfringens.

Clostridium perfringens, a Gram-positive bacterium, causes intestinal diseases in humans and livestock through its toxins, related to alpha toxin (CPA), beta toxin (CPB), C. perfringens enterotoxin (CPE), epsilon toxin (ETX), Iota toxin (ITX), and necrotic enteritis B-like toxin (NetB). These toxins disrupt intestinal barrier, leading to various cell death mechanisms such as necrosis, apoptosis, and necroptosis. Additionally, non-toxin factors like adhesins and degradative enzymes contribute to virulence by enhancing colonization and survival of C. perfringens. A vicious cycle of intestinal barrier breach, misregulated cell death, and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. Understanding these mechanisms is essential for developing targeted therapies against C. perfringens-associated intestinal diseases.

Effects of low-volume functional and running high-intensity interval training on physical fitness in young adults with overweight/obesity.

Objectives: This study examined and compared the effects of functional and running high-intensity interval training (HIIT) on body composition, cardiorespiratory fitness, and muscular fitness of young adults with overweight or obesity. Methods: Forty-five participants (22.1 ± 2.1 years, BMI = 25.2 ± 1.0 kg/m2) were assigned to functional HIIT (HIIT-F; n = 15), running HIIT (HIIT-R; n = 15), or non-training control group (CON; n = 15). Participants in HIIT-F and HIIT-R performed functional exercise based-HIIT (four sets of all-out whole-body exercises including jumping jacks, squats, twist jumps and mountain climbers, et al.) and running HIIT (four sets of running on a treadmill) for 12 weeks, respectively. Body composition, muscular fitness, and cardiorespiratory fitness were assessed pre and post intervention. Results: Both HIIT-F and HIIT-R significantly improved the body composition and cardiorespiratory fitness, with HIIT-F induced greater improvements in lean mass (+1.623 vs. -1.034 kg, p < 0.001), back strength (+6.007 vs. +3.333 kg, p < 0.01), and push-ups (+5.692 vs. 1.923 reps, p < 0.001) than that in HIIT-R. HIIT-R reduced more visceral fat area (VFA) (-11.416 vs. -4.338 cm2, p = 0.052) and induced similar improvement in cardiorespiratory fitness (VO2max, +2.192 vs. +2.885 mL/kg/min, p = 0.792) with HIIT-F. Conclusion: Twelve weeks of HIIT-R or HIIT-F improved physical fitness among young adults with overweight or obesity. Despite the similar impact on cardiorespiratory fitness, HIIT-F generates a better positive effect on muscular fitness relative to HIIT-R, which could be partly explained by the greater increase in lean mass after HIIT-F intervention.

Resveratrol-derived inhibitors of the E3 ubiquitin ligase PELI1 inhibit the metastasis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), as the most challenging subtype of breast cancer, exerts highly invasive ability and metastatic nature to the lymph nodes, which is correlated with poor survival rates among patients. Pellino-1 (PELI1) is an E3 ubiquitin ligase involved in tumor invasion and metastasis, and has the potential to be developed as a novel therapeutic target for TNBC. In this study, we identified a potent inhibitor of PELI1, namely compound 3d, on the basis of natural stilbene framework through medicinal chemistry approaches. This novel PELI1 inhibitor 3d showed potent binding affinity to PELI1 (Kd 8.2 µM) in fluorescence quenching assay, and markedly interrupted the interaction of PELI1 and SNAIL/SLUG confirmed by co-immunoprecipitation. Moreover, 3d exhibited potent antitumor activity in inhibiting tumor cell migration in scratch wound healing assay without affecting cell proliferation in vitro, and down-regulated the downstream EMT-effectors of PELI1 as assessed by western blotting. In the experimental lung metastasis model, 3d showed anti-TNBC metastasis efficacy without observable toxicity in vivo.

Effects of Roasting Temperatures on Peanut Oil and Protein Yield Extracted via Aqueous Enzymatic Extraction and Stability of the Oil Body Emulsion.

Oil body emulsions (OBEs) affect the final oil yield as an intermediate in the concurrent peanut oil and protein extraction process using an aqueous enzyme extraction (AEE) method. Roasting temperature promotes peanut cell structure breakdown, affecting OBE composition and stability and improving peanut oil and protein extraction rates. Therefore, this study aimed to investigate the effects of pretreatment at different roasting temperatures on peanut oil and protein yield extracted through AEE. The results showed that peanut oil and protein extraction rates peaked at 90 °C, 92.21%, and 77.02%, respectively. The roasting temperature did not change OBE composition but affected its stability. The OBE average particle size increased significantly with increasing temperature, while at 90 °C, the zeta potential peaked, and the interfacial protein concentration hit its lowest, indicating OBE stability was the lowest. Optical microscopy and confocal laser scanning microscopy confirmed the average particle size findings. The oil quality obtained after roasting treatment at 90 °C did not differ significantly from that at 50 °C. The protein composition remained unaffected by the roasting temperature. Conclusively, the 90 °C roasting treatment effectively improved the yield of peanut oil extracted using AEE, providing a theoretical basis for choosing a suitable pretreatment roasting temperature.

Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice.

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium. Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment (P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice (P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium-induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

Recent advances in soybean protein processing technologies: A review of preparation, alterations in the conformational and functional properties.

Currently, growing concerns about sustainable development and health awareness have driven the development of plant-based meat substitutes. Soybean proteins (SPs) are eco-friendly and high-quality food sources with well-balanced amino acids to meet consumer demand. The functionality and physicochemical attributes of SPs can be improved by appropriate processing and modification. With the burgeoning advances of modern processing technologies in the food industry, a multitude of functional foods and ingredients can be manufactured based on SPs. This review mainly highlights the conformational changes of SPs under traditional and emerging processing technologies and the resultant functionality modifications. By elucidating the relationship between processing-induced structural and functional alterations, detailed and systematic insights are provided regarding the exploitation of these techniques to develop different nutritional and functional soybean products. Some popular methods to modify SPs properties are discussed in this paper, including thermal treatment, fermentation, enzyme catalysis, high hydrostatic pressure, high-intensity ultrasound, atmospheric cold plasma, high-moisture extrusion, glycosylation, pulsed ultraviolet light and interaction with polyphenols. Given these processing technologies, it is promising to expand the application market for SPs and boost the advancement of the soybean industry.

Lignin Promotes Mycelial Growth and Accumulation of Polyphenols and Ergosterol in Lentinula edodes.

It has been demonstrated that lignin was efficiently degraded by Lentinula edodes (L. edodes). However, the process of lignin degradation and utilization by L. edodes has not been discussed in detail. Therefore, the effects of lignin on L. edodes mycelium growth, chemical compositions, and phenolic profiles were investigated herein. It has been revealed that 0.10% lignin acted as the most effective concentration to accelerate mycelia growth, which yielded the highest biomass of 5.32 ± 0.07 g/L. Furthermore, a 0.10% concentration of lignin promoted the accumulation of phenolic compounds, especially protocatechuic acid, with peak value of 48.5 ± 1.2 µg/g. In contrast, the higher concentration of lignin (0.20%) exerted an inhibitory effect on the growth of L. edodes. Overall, the application of lignin at the optimal concentration of 0.10% could not only enhance the mycelial growth but also accumulate the phenolic acids and raise the nutritional and medical values of L. edodes.

Research advances in the application of metabolomics in exercise science.

Exercise training can lead to changes in the metabolic composition of an athlete's blood, the magnitude of which depends largely on the intensity and duration of exercise. A variety of behavioral, biochemical, hormonal, and immunological biomarkers are commonly used to assess an athlete's physical condition during exercise training. However, traditional invasive muscle biopsy testing methods are unable to comprehensively detect physiological differences and metabolic changes in the body. Metabolomics technology is a high-throughput, highly sensitive technique that provides a comprehensive assessment of changes in small molecule metabolites (molecular weight <1,500 Da) in the body. By measuring the overall metabolic characteristics of biological samples, we can study the changes of endogenous metabolites in an organism or cell at a certain moment in time, and investigate the interconnection and dynamic patterns between metabolites and physiological changes, thus further understanding the interactions between genes and the environment, and providing possibilities for biomarker discovery, precise training and nutritional programming of athletes. This paper summaries the progress of research on the application of exercise metabolomics in sports science, and looks forward to the future development of exercise metabolomics, with a view to providing new approaches and perspectives for improving human performance, promoting exercise against chronic diseases, and advancing sports science research.

Mendelian randomization study supports the causal association between serum cystatin C and risk of diabetic nephropathy.

Aims: Cystatin C, an inhibitor of cysteine protease, has been used as a biomarker for estimating glomerular filtration rate. However, the causal relation between cystatin C and diabetic nephropathy remains uncertain. Methods: We assessed the causal effect of cystatin C together with other five serum biomarkers including KIM-1, GDF-15, TBIL, uric acid, and Scr on diabetic nephropathy by Mendelian randomization (MR) analysis. 234 genetic variants were selected as instrumental variables to evaluate the causal effect of cystatin C (NGWAS=361194) on diabetic nephropathy (Ncase/Ncontrol up to 3283/210463). Multivariable MR (MVMR) was performed to assess the stability of cystatin C's causal relationship. Two-step MR was used to assess the mediation effect of BMI and SBP. Results: Among the six serum biomarkers, only cystatin C causally associated with diabetic nephropathy (IVW OR: 1.36, 95%CI [1.15, 1.61]). After adjusting for the potential confounders BMI and SBP, cystatin C maintained its causal effect on the DN (OR: 1.17, 95%CI [1.02, 1.33]), which means that the risk of DN increased by 17% with an approximate 1 standard deviation (SD) increment of serum cystatin C level. Two-step MR results indicated that BMI might mediate the causal effect of cystatin C on diabetic nephropathy. Interpretation: Our findings discovered that cystatin C was a risk factor for diabetic nephropathy independent of BMI and SBP in diabetes mellitus patients. Future research is required to illustrate the underlying mechanism and prove targeting circulating cystatin C could be a potential therapy method.

SIRT2 regulates proliferation and chemotherapy response of MLL-ENL-driven acute myeloid leukemia.

Both MLL-AF9 and MLL-ENL leukemia fusion proteins drive oncogenic transformation of hematopoietic cells through their N-terminal DNA/histone binding mixed-lineage leukemia 1 domain and C-terminal fragment of AF9 or ENL containing an unstructured linker region and the ANC1 homology domain, which recruits transcription factors. Despite of their structural similarity, acute myeloid leukemia (AML) patients bearing MLL-ENL show more adverse outcomes compared to those with MLL-AF9. We recapitulated the clinical patterns of these two MLL-fusions driven AMLs using murine models and found that MLL-ENL AML cells showed slower cell cycle progression and more resistance to standard chemotherapy than MLL-AF9 cells. These phenotypes were primarily controlled by the linker regions of ENL and a highly conserved lysine residue K469 within. Substitution of K469 with an acetylated mimic glutamine abolished the ability of MLL-ENL to suppress proliferation and promote chemo-resistance. We showed that deacetylase Sirt2 might act as an upstream regulator of MLL-ENL. Deletion of Sirt2 promoted proliferation of AML cells with either MLL fusions. Importantly, loss of Sirt2 greatly enhanced the sensitivity of the MLL-ENL AML cells to chemo-treatment. Taken together, our study uncovered a unique regulatory role of Sirt2 in leukemogenesis and suggested targeting SIRT2 as a new way to sensitize MLL-ENL AML patience for chemotherapy.

DAK inhibits MDA5-mediated signaling in the antiviral innate immunity of black carp.

Dihydroxyacetone kinase (DAK) functions as a negative regulator of melanoma differentiation-associated gene 5 (MDA5)-mediated interferon (IFN) production in human. To explore its role in teleost fish, DAK homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized in this paper. The transcription of black carp DAK (bcDAK) variated in host cells in response to LPS, poly (I:C) and virus stimulation, and bcDAK was majorly distributed in the cytoplasm. Overexpressed bcDAK in EPC cells showed little IFN promoter-inducing ability in the reporter assay and no antiviral activity in plaque assay. When co-expressed with black carp MDA5 (bcMDA5) in EPC cells, bcDAK obviously inhibited bcMDA5-mediated IFN promoter transcription in reporter assay and the antiviral activity in plaque assay. The knockdown of bcDAK enhanced the antiviral activity of the host cells. The association between bcDAK and bcMDA5 has been identified through immunofluorescent staining and co-immunoprecipitation (co-IP) assay. Thus, the data generated in this study support the conclusion that black carp DAK interacts with MDA5 and negatively regulates MDA5-mediated antiviral signaling.

Etomidate inhibits cell proliferation and induces apoptosis in A549 non-small cell lung cancer cells via downregulating WWP2.

Etomidate (ETO) is a commonly used intravenous anesthetic that has been reported to exert a tumor suppressive effect in several types of cancer. The present study aimed to investigate the effect of ETO on cell proliferation and apoptosis in non-small cell lung cancer (NSCLC) cells and elucidate its potential mechanism of action. Therefore, Cell Counting Kit-8 assay was performed to evaluate the effect of different concentrations of ETO (0, 1, 2 or 3 µg/ml) on A549 cell viability. In addition, the possible interaction between ETO and WW domain containing E3 ubiquitin protein ligase 2 (WWP2) was predicted using the STITCH database. Additionally, a stable WWP2-overexpressing A549 cell line was constructed by transfecting A549 cells with the pcDNA3.1-WWP2 plasmid. Cell proliferation and apoptosis were assessed using colony formation and TUNEL assays, respectively. The mRNA and protein expression levels of the apoptosis-related proteins Bcl-2, Bax, caspase 3 and cleaved-caspase 3 were determined by reverse transcription-quantitative PCR and western blotting. In addition, the expression and phosphorylation levels of proliferation-associated genes (PCNA and Ki-67) and proteins in the PI3K/Akt pathway were analyzed by western blotting. The results showed that treatment with ETO attenuated the cell viability and proliferation of A549 cells. ETO also promoted cell apoptosis and decreased the expression of the anti-apoptotic protein Bcl-2, whilst increasing that of pro-apoptotic proteins Bax and cleaved caspase 3 in a dose-dependent manner. Furthermore, ETO was found to negatively regulate the expression of WWP2, such that WWP2 overexpression reversed the potentiating effects of ETO on cell apoptosis. In addition, ETO promoted the expression of PTEN and reduced the phosphorylation levels of the PI3K/AKT pathway-related proteins. These effects aforementioned could also be reversed by WWP2 overexpression. Therefore, data from the present study suggest that ETO can attenuate the progression of NSCLC through by the PI3K/AKT pathway, specifically by targeting WWP2. These findings may provide a novel target for the treatment of NSCLC.

Effect of soybean oil content on textural, rheological, and microstructural properties of WBAXs-SPI emulsion-filled gels.

This study aimed to prepare wheat bran arabinoxylans-soy protein isolate (WBAXs-SPI) emulsion-filled gels with different oil contents and investigate their rheological, textural, water-holding capacity (WHC), and microstructural properties. The rheological analysis results showed that the maximum correlation interaction occurs when the soybean oil concentration was 10%, and the elastic modulus (G') reaches the highest value of 13,562 Pa. Interestingly, the WHC and texture change trend of WBAXs-SPI emulsion-filled gel were consistent with rheology. Meanwhile, confocal laser scanning microscopy (CLSM) observation indicated that the emulsion-filled gels formed an interpenetrating polysaccharide-protein complex network system. Therefore, the filling emulsion performance could be adjusted by changing the concentration of oil droplets as the active filler. This provides the possibility of developing new food materials encapsulating fat-soluble substances with a low oil rate and more stable structure.

Hydrogen Gas Alleviates Sepsis-Induced Brain Injury by Improving Mitochondrial Biogenesis Through the Activation of PGC-α in Mice.

ABSTRACT: Sepsis-associated encephalopathy (SAE) affects approximately one-third of septic patients, and there is a lack of effective therapeutics for SAE. Hydrogen gas is a new medical gas that exerts anti-inflammation, antioxidation, and anti-apoptotic effects and can effectively protect septic mice. Mitochondrial dysfunction, which can be improved by mitochondrial biogenesis, is a type of molecular pathology in sepsis. Peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), which can be inhibited by SR-18292, is the key regulatory factor of mitochondrial biogenesis. Therefore, we investigated the effects of hydrogen gas on mitochondrial function and mitochondrial biogenesis in mice with SAE and the related regulatory mechanisms. Cecal ligation and puncture was used to induce sepsis in mice. The mice with hydrogen gas therapy were exposed to 2% H2 inhalation for 1 h beginning at both 1 and 6 h after operation, and mice were also injected with a PGC-1α inhibitor, SR-18292. We recorded the 7-day survival rates of the mice and detected their cognitive function using a Y-maze test. The Nissl bodies in the CA1 region of hippocampus were observed by Nissl staining, and the apoptotic cells were observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay staining. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, and mitochondrial respiratory chain complexes I and II were analyzed using commercial kits. The mitochondrial morphology was observed by transmission electron microscopy. The expression levels of PGC-1α, nuclear respiratory factor 2 (NRF2), and mitochondrial transcription factor A (Tfam) were detected by Western blot analysis. The present study showed that hydrogen gas therapy increased the 7-day survival rate, improved cognitive function, increased the mitochondrial function (MMP, ATP level, complex I activity) and expression of mitochondrial biogenesis parameters (PGC-1α, NRF2, Tfam). However, the injection of SR-18292 (a PGC-1α inhibitor) decreased mitochondrial function, PGC-1α activation, and expression of NRF2 and Tfam. Therefore, these results indicate that hydrogen gas alleviates sepsis-induced brain injury in mice by improving mitochondrial biogenesis through the activation of PGC-1α.

Verteporfin Promotes the Apoptosis and Inhibits the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Downregulating SULT2B1 Expression.

BACKGROUND Cervical cancer threatens women's health worldwide. Verteporfin (VP), a small-molecule YAP1 inhibitor, inhibits cancer cell growth. This study investigated whether VP could inhibit the proliferation and promote the apoptosis of cervical cancer cells by decreasing SULT2B1 expression. MATERIAL AND METHODS Normal and cancerous cervical cell proliferation after VP treatment was detected by CCK-8 assay. HeLa cell migration, invasion, and apoptosis after VP treatment and transfection were analyzed by wound healing assay, transwell assay, and TUNEL assay, respectively. The expression of related proteins was determined by western blot analysis. Western blot and RT-qPCR analysis detected mRNA and protein expression of SULT2B1. RESULTS Different VP concentrations (0.5, 1, 2, and 5 µM) inhibited the viability of HeLa cells and had no obvious effect on H8 cells. Therefore, 5 µM VP was selected for subsequent experiments. VP inhibited the proliferation, migration, and invasion of HeLa cells and promoted their apoptosis. Bcl-2 expression decreased, and expression of Bax, caspase-3, and caspase-9 in VP-treated HeLa cells increased. SULT2B1 expression increased in cervical cancer cells compared with normal cervical cells. Furthermore, SULT2B1 expression increased in HeLa cells and VP suppressed SULT2B1 expression. SULT2B1 overexpression reduced the inhibiting effect of VP on the proliferation, migration, and apoptosis of HeLa cells, and reduced VP effect on apoptosis of HeLa cells. SULT2B1 overexpression upregulated the Bcl-2 expression and downregulated the expression of Bax, caspase-3, and caspase-9 in VP-treated HeLa cells. CONCLUSIONS VP inhibited the proliferation, migration, and invasion and promoted apoptosis of cervical cancer cells by decreasing SULT2B1 expression.

Exogenous hydrogen sulfide alleviates surgery-induced neuroinflammatory cognitive impairment in adult mice by inhibiting NO signaling.

BACKGROUND: To investigate the effect and mechanisms of exogenous hydrogen sulfide in surgery-induced neuroinflammatory cognitive dysfunction. METHODS: C57BL/6 J male mice (n = 140) were used and randomly divided into seven groups: the sham group, surgery group, GYY4137 group, L-NAME group, surgery+GYY4137 group, surgery +L-NAME group, and surgery+GYY4137 + L-NAME group. After the interventions, open field tests (OFT) and the Morris water maze (MWM) test were conducted to evaluate learning and memory abilities in the mice. ELISAs, nitrate reductase assays, and Western blots (WB) were conducted to evaluate interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase (SOD) levels. Furthermore, the expression level of microglial marker ionized calcium binding adaptor molecule 1 (IBA) in the hippocampal CA1 and CA3 areas was detected by an immunohistochemical (IHC) assay and apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP end-labeling (TUNEL) staining kits. RESULTS: We found that surgery induced neuroinflammatory cognitive dysfunction, oxidative stress, microglial activation, and cell apoptosis in the hippocampus. Moreover, following surgery, NO and iNOS levels were elevated in the hippocampus. Notably, all the effects caused by surgery were reversed by the H2S donor GYY4137 or the iNOS inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME). However, the combined application of GYY4137 and L-NAME was not superior to treatment with either agent alone and the effect of GYY4137 was similar to that of L-NAME. CONCLUSION: The long-acting hydrogen sulfide donor GYY4137 had an ability to reversed the cognitive deficits and inflammation caused by carotid artery exposure surgery. This implies that NO signaling pathways might participate in this process. These results indicate that exogenous H2S may be a promising therapy for POCD.

Dexmedetomidine protects against sepsis­associated encephalopathy through Hsp90/AKT signaling.

Sepsis­associated encephalopathy (SAE) is characterized by neuronal apoptosis and changes in mental status. Accumulating evidence has. indicated that dexmedetomidine is capable of protecting the brain against external stimuli and improving cognitive dysfunctions. The aim of the present study was to investigate the possible neuroprotective effects of dexmedetomidine on SAE and the role of heat­shock protein (Hsp)90/AKT signaling in an experimental model of sepsis. The SAE model was established by cecal ligation and perforation (CLP) in vivo and lipopolysaccharide (LPS) treated hippocampal neuronal cultures in vitro. It was found that dexmedetomidine inhibited caspase­3, but increased the expression level ofBcl­2 in CLP rats. CLP rats also exhibited a decreased level of phosphorylated AKT Thr 308 and Hsp90, and their expression could be reversed by treatment with dexmedetomidine. Additionally, application of dexmedetomidine increased cell survival and decreased neuronal apoptosis in vitro. Furthermore, the neuroprotective effects of dexmedetomidine could be reversed by 17­AAG (a Hsp90 inhibitor), or wortmannin (a PI3K inhibitor). Analysis of TUNEL staining indicated that dexmedetomidine improved LPS­induced neuronal apoptosis, which could be eradicated by AKT short hairpin RNA transfection, prazosin or yohimbine. Finally, dexmedetomidine ameliorated both the emotional and spatial cognitive disorders without alteration in locomotor activity. The present findings suggested that dexmedetomidine may protect the brain against SAE, and that the Hsp90/AKT pathway may be involved in this process.

miR­210­3p regulates cell growth and affects cisplatin sensitivity in human ovarian cancer cells via targeting E2F3.

The potential role of microRNA (miR)­210­3p in carcinogenesis and the cisplatin sensitivity of ovarian cancer were evaluated in the present study. The relative expression levels of miR­210­3p in cisplatin­sensitive SKOV­3 cells and cisplatin­resistant SKOV­3/DDP cells were determined using reverse transcription­quantitative polymerase chain reaction analysis. miR­210­3p mimics and inhibitors were transfected into SKOV­3/DDP cells. Cell Counting Kit­8, scratch and Transwell invasion assays and flow cytometry were conducted to evaluate the role of miR­210­3p in ovarian cancer cells. A luciferase reporter assay was used to verify the association between miR­210­3p and E2F transcription factor 3 (E2F3). Drug sensitivity was evaluated by treating the cells with cisplatin. The expression level of miR­210­3p was lower in SKOV­3/DDP cells than in SKOV­3 cells. Compared with the untransfected control, SKOV­3 cells transfected with miR­210­3p exhibited a significantly higher survival rate. The overexpression of miR­210­3p inhibited SKOV­3/DDP cell proliferation, migration and invasion, and promoted cell apoptosis. By contrast, the inhibition of miR­210­3p promoted cell migration and invasion. The luciferase reporter assay confirmed that E2F3 was a direct target gene of miR­210­3p. Cisplatin treatment resulted in a sharp decrease in the survival rate of SKOV­3/DDP cells transfected with the miR­210­3p mimics. The decrease in cell survival rate caused by the overexpression of miR­210­3p was rescued by the overexpression of E2F3 in SKOV­3/DDP cells. Taken together, these results suggest that miR­210­3p may act as a tumor suppressor in ovarian cancer cells and affect the sensitivity of cells to cisplatin by directly targeting E2F3. This indicates its potential use as a therapeutic target for improving drug resistance in ovarian cancer.