Mechanistic studies on the alleviation of ANIT-induced cholestatic liver injury by Polygala fallax Hemsl. polysaccharides.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a traditional folk medicine commonly used by ethnic minorities in the Guangxi Zhuang Autonomous Region, and has a traditional application in the treatment of liver disease. Polygala fallax Hemsl. polysaccharides (PFPs) are of interest for their potential health benefits. AIM OF THIS STUDY: This study explored the impact of PFPs on a mouse model of cholestatic liver injury (CLI) induced by alpha-naphthyl isothiocyanate (ANIT), as well as the potential mechanisms. MATERIALS AND METHODS: A mouse CLI model was constructed using ANIT (80 mg/kg) and intervened with different doses of PFPs or ursodeoxycholic acid. Their serum biochemical indices, hepatic oxidative stress indices, and hepatic pathological characteristics were investigated. Then RNA sequencing was performed on liver tissues to identify differentially expressed genes and signaling pathways and to elucidate the mechanism of liver protection by PFPs. Finally, Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to verify the differentially expressed genes. RESULTS: Data analyses showed that PFPs reduced the levels of liver function-related biochemical indices, such as ALT, AST, AKP, TBA, DBIL, and TBIL. PFPs up-regulated the activities of SOD and GSH, down-regulated the contents of MDA, inhibited the release of IL-1ß, IL-6, and TNF-α, or promoted IL-10. Pathologic characterization of the liver revealed that PFPs reduced hepatocyte apoptosis or necrosis. The RNA sequencing indicated that the genes with differential expression were primarily enriched for the biosynthesis of primary bile acids, secretion or transportation of bile, the reactive oxygen species in chemical carcinogenesis, and the NF-kappa B signaling pathway. In addition, the results of qRT-PCR and Western blotting analysis were consistent with those of RNA sequencing analysis. CONCLUSIONS: In summary, this study showed that PFPs improved intrahepatic cholestasis and alleviated liver damage through the modulation of primary bile acid production, Control of protein expression related to bile secretion or transportation, decrease in inflammatory reactions, and inhibition of oxidative pressure. As a result, PFPs might offer a hopeful ethnic dietary approach for managing intrahepatic cholestasis.

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation.

Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia-reperfusion (I/R)-induced intestinal injury, we clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Sixty specific pathogen free (SPF)-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12). Six rats were randomly selected at 6 hour (h) and 24 h after I/R. Inferior vena cava blood specimens were collected from the portal vein (PV) opening at 6 h and 24 h. The concentrations of serum malondialdehyde (MDA), serum interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Ileal tissue was obtained from the PV opening in rats in each group at 6 h and 24 h, and ileal tissue sections were observed under light microscopy. The contents of intestinal MDA, superoxide dismutase (SOD), glutathione(GSH), glutathione peroxidase 4 (GPX4), and tissue iron were determined by ELISA, and the expression of GPX4 and the cysteine glutamate reverse transporter light chain protein (xCT) was determined by Western blot. The experimental results show that ferroptosis is involved in the pathophysiological process of intestinal injury induced by cold hepatic ischemia-reperfusion in AOLT rats. In addition, SAS (500 mg/kg) may inhibit the cystine/glutamate antiporters (System Xc¯)/GSH/GPX4 signal axis in intestinal injury induced by cold I/R in rat AOLT liver, or iron overload after reperfusion, causing a massive accumulation of L-ROS and activating cellular ferroptosis, further aggravate the intestinal injury.

Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke.

Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.

HIF-1α-regulated lncRNA-TUG1 promotes mitochondrial dysfunction and pyroptosis by directly binding to FUS in myocardial infarction.

Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.

3D Metallic Ti@Ni0.85 Se with Triple Hierarchy as High-Efficiency Electrocatalyst for Overall Water Splitting.

In this study, Ti@Ni0.85 Se electrodes with a triple hierarchy architecture were designed, and their applications in electrocatalytic water splitting were studied. The 3D electrode is comprised of three types of structures including the bottom square Ti mesh structure as the conductive substrate, a vertical and uniform Ni0.85 Se nanosheet arrays structure in the intermediate section, and the topmost Ni0.85 Se flower structure. This triple hierarchy architecture is binder-free, conductive, and has a particular feature of enlarged surface areas, exposing more active sites, promoting mass- and charge-transfer, and accelerating dissipation of gases generated during water electrolysis. Moreover, DFT calculations confirmed that the Ni0.85 Se possesses metallic character, which further promotes the charge transfer of the electrocatalyst. Benefiting from this special structure and metallic character, the electrode displays a superior activity of 10 mA cm-2 at 120 mV hydrogen evolution reaction overpotential and 30 mA cm-2 at 270 mV oxygen evolution reaction overpotential. By using this electrode as a bifunctional electrocatalyst, an alkali electrolyzer affords a water splitting current of 10 mA cm-2 at a cell voltage of 1.66 V.

Act values after neutralization lower than pre-heparinization act leads to lower operative times, bleeding, and post-operative transfusions in cabg pa

Abstract Objective: To evaluate if lower activated coagulation time (ACT) value after neutralization than preoperative ACT value was effective in reducing bleeding, operative times, and post-operative transfusions in patients underwent coronary artery bypass grafting (CABG). Methods: Retrospective selection of 398 patients from January 2014 to May 2017. Patients were divided into 2 groups according to final ACT after neutralization: A - final ACT lower than preoperative ACT; and B - final ACT higher than or equal to preoperative ACT. Hemostatic time, intraoperative blood loss, ACT after final neutralization, mediastinal blood loss, and transfusion requirements were observed. Results: The hourly blood loss in the Group A was generally lower than in the Group B at first 3 hours, which has significant difference (P<0.05). However, there was no difference after 3 hours between the two groups. Operative time, intraoperative blood loss, mediastinal blood loss, transfusion requirements, and drainage in the first postoperative 12 hours in the Group A were lower than in Group B, which has significant difference (P<0.05). Conclusion: As a result, final ACT values lower than pre-heparinization ACT values are safe and lead to lower operative times, bleeding, and post-operative transfusions.

Crocin Attenuates Oxidative Stress and Myocardial Infarction Injury in Rats.

Oxidative stress and excessive nitric oxide (NO) production play considerable roles in infarction-induced injury impairing cardiac functions. Crocin is the active constituent of Crocus sativus (saffron) with antioxidant properties and has protective effects against disturbances induced by ischemia in many organs. The present study aimed to investigate the protective effects and the underlying mechanisms of crocin on myocardial infarction (MI)-induced injury in rats in vivo. MI rats were intraperitoneally injected with crocin at different doses for seven successive days after coronary ligation. Infarct size, hemodynamic studies, and capillary density were evaluated. Levels of oxidative stress, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and their corresponding phosphorylation expressions were then measured. Crocin decreased infarct size, left ventricular (LV) end-diastolic pressure, and LV minimum dP/dt while increased LV maximum dP/dt and percentage of LV fractional shortening dose dependently. Capillary density was markedly increased after crocin treatment. Crocin enhanced superoxide dismutase activity and reduced malondialdehyde levels as well as inhibited excessive production of NO through downregulating iNOS as well as upregulating eNOS during MI-induced injury. This study reveals that crocin improves MI-induced impairments in cardiac function, which is associated with its antioxidant properties.

ACT Values after Neutralization Lower than Pre-heparinization ACT Leads to Lower Operative Times, Bleeding, and Post-Operative Transfusions in CABG Patients: an Observational Study.

OBJECTIVE: To evaluate if lower activated coagulation time (ACT) value after neutralization than preoperative ACT value was effective in reducing bleeding, operative times, and post-operative transfusions in patients underwent coronary artery bypass grafting (CABG). METHODS: Retrospective selection of 398 patients from January 2014 to May 2017. Patients were divided into 2 groups according to final ACT after neutralization: A - final ACT lower than preoperative ACT; and B - final ACT higher than or equal to preoperative ACT. Hemostatic time, intraoperative blood loss, ACT after final neutralization, mediastinal blood loss, and transfusion requirements were observed. RESULTS: The hourly blood loss in the Group A was generally lower than in the Group B at first 3 hours, which has significant difference (P<0.05). However, there was no difference after 3 hours between the two groups. Operative time, intraoperative blood loss, mediastinal blood loss, transfusion requirements, and drainage in the first postoperative 12 hours in the Group A were lower than in Group B, which has significant difference (P<0.05). CONCLUSION: As a result, final ACT values lower than pre-heparinization ACT values are safe and lead to lower operative times, bleeding, and post-operative transfusions.

Dexmedetomidine ameliorates the inflammatory immune response in rats with acute kidney damage.

It has been demonstrated that dexmedetomidine (Dex) can protect patients with acute kidney injury from experiencing further tissue damage, however its mechanism of action remains unclear. The present study investigated the immune modulatory functions of Dex in rats with acute kidney injury (AKI) induced via injection of lipopolysaccharide into the tail vein. ELISA analysis showed that Dex reduced the levels of inflammatory cytokines in rats with AKI in a dose dependent manner. Furthermore, the regulatory effects of Dex on cytokine production disappeared when the α-2 adrenergic receptor antagonist Yohimbine (YOH) was added. For a detailed investigation on how Dex regulates the immune response in rats with AKI, the impact of Dex on the viability of splenocytes and lymphocytes was determined and it was determined that Dex did not influence splenocyte and lymphocyte viability. In addition, ELISA tests showed that Dex regulated the production of the T-helper (Th) 17 cytokines interleukin (IL)-17 and IL-23, but not the Th1 cytokine tumor necrosis factor α, in splenocytes and lymphocytes. To confirm whether Dex functioned as an α-2-adrenergic receptor in these immune regulations, YOH was administered together with Dex. When Dex and YOH were administered together, the regulatory functions of Dex were reduced, confirming that Dex acted as an agonist on the α-2-adrenergic receptor. Thus the results of the current study may provide novel insights regarding how Dex modulates immune functions in AKI.

Surface oxygen vacancy induced solar light activity enhancement of a CdWO4/Bi2O2CO3 core-shell heterostructure photocatalyst.

A CdWO4/Bi2O2CO3 core-shell heterostructure photocatalyst was fabricated via a facile two-step hydrothermal process. Flower-like Bi2O2CO3 was synthesized and functioned as the cores on which CdWO4 nanorods were coated as the shells. Photoluminescence (PL) spectra and electron paramagnetic resonance (EPR) demonstrate that the CdWO4/Bi2O2CO3 core-shell heterostructure photocatalyst possesses a large amount of oxygen vacancies, which induce defect levels in the band gap and help to broaden light absorption. The photocatalyst exhibits enhanced photocatalytic activity for Rhodamine B (RhB), methylene blue (MB), methyl orange (MO), and colorless contaminant phenol degradation under solar light irradiation. The heterostructured CdWO4/Bi2O2CO3 core-shell photocatalyst shows drastically enhanced photocatalytic properties compared to the pure CdWO4 and Bi2O2CO3. This remarkable enhancement is attributed to the following three factors: (1) the presence of oxygen vacancies induces defect levels in the band gap and increases the visible light absorption; (2) intimate interfacial interactions derived from the core-shell heterostructure; and (3) the formation of the n-n junction between the CdWO4 and Bi2O2CO3. The mechanism is further explored by analyzing its heterostructure and determining the role of active radicals. The construction of high-performance photocatalysts with oxygen vacancies and core-shell heterostructures has great potential for degradation of refractory contaminants in water with solar light irradiation.

Evaluation of high-concentration sevoflurane for induction and nasotracheal intubation without muscle relaxant for infants with different pulmonary blood flow undergoing surgery for congenital heart diseases.

BACKGROUND: Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases. METHODS: Fifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded. RESULTS: Times to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively. CONCLUSIONS: Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF. However, nasotracheal intubation without muscle relaxant after induction with high concentration sevoflurane is less successful and less satisfactory for infants with DPBF and should be used with caution in this patient group.