Micromechanical Observation and Numerical Simulation for Local Deformation Evolution of Duplex Stainless Steel.

The characteristics of local strain distribution and evolution of duplex stainless steel during the tensile process were studied using the digital image correlation (DIC) technique. In addition, the finite element inversion of nanoindentation experiments of austenitic and ferrite phases in duplex stainless steel was carried out to obtain the stress-strain response of the two phases. Further, based on the representative volume element (RVE) and the material parameters obtained from the finite element inversion method, the local stress and strain behavior of duplex stainless steel at microscale was simulated numerically. The results fit well with the experiments, showing that the austenite phase is softer than ferrite phase, with the larger strain zone concentrated in the austenite phase and the larger stress zone concentrated in the ferrite phase. The grain boundaries are prone to obvious stress and strain concentrations. The local stress and strain distributions are influenced by the shape and interaction of the grains, while the distribution features become more obvious as the load increases. The research results effectively reveal the two-phase interaction and local failure mechanism of duplex stainless steel, and may provide a reference for material preparation and safety design of related structures.

Intracoronary Ultrasound Imaging Combined with Traditional Chinese Medicine Nursing Applied in the Treatment of Coronary Heart Disease Patients with Phlegm and Blood Stasis Syndrome.

This study was to explore the effect of traditional Chinese medicine (TCM) nursing intervention based on intracoronary ultrasound imaging on patients with coronary heart disease (CHD) and phlegm and blood stasis syndrome (PBSS). 100 hospitalized patients with CHD with Qi deficiency and blood stasis syndrome (QDBSS) were rolled into the experimental (Exp) group (routine nursing intervention) and control (Ctrl) group (TCM nursing intervention, syndrome differentiation nursing), with 50 patients in each group. They underwent the intracoronary ultrasound imaging scanning. The results showed that after intervention, the plaque load (45.08 ± 6.02%), plaque eccentricity index (0.47 ± 0.08%), vascular remodeling index (0.53 ± 0.11%), and vascular external elastic membrane area (8.67 ± 3.06 mm2) of the Exp group were notably inferior to those of the Ctrl group (60.22 ± 5.82%, 0.59 ± 0.08%, 0.71 ± 0.09%, and 10.56 ± 2.31 mm2). The total effective rate in the Exp group (88%) was greatly superior to that of the Ctrl group (68%). In terms of TCM symptom scores, the TCM symptom scores of chest pain, chest tightness, and shortness of breath in the Exp group after intervention (1.07 ± 0.21 points, 0.75 ± 0.27 points, and 0.58 ± 0.12 points) were notably inferior to those in the Ctrl group (1.62 ± 0.28 points, 1.03 ± 0.21 points, and 0.79 ± 0.14 points). In the Exp group, after intervention, the degree of physical activity limitation (67.05 ± 5.08 points), the stable state of angina pectoris (65.28 ± 3.76 points), the frequency of angina pectoris attack (85.92 ± 2.97 points), the degree of treatment satisfaction (75.39 ± 5.94 points), the cognition score of disease (63.56 ± 5.84 points), the levels of triglyceride (1.27 ± 0.41 mmol/L), and total cholesterol (2.24 ± 0.41 mmol/L) were remarkably inferior to the Ctrl group (52.97 ± 4.31 points, 50.77 ± 4.69 points, 71.36 ± 3.77 points, 64.08 ± 5.64 points, 51.77 ± 6.33 points, 2.09 ± 0.57 mmol/L, and 3.06 ± 0.84 mmol/L) (P < 0.05). It suggested that intracoronary ultrasound imaging can clearly display the coronary plaques of patients and accurately evaluate the clinical efficacy of patients with CHD. The TCM nursing program can greatly improve the angina symptoms and quality of life of patients with CHD and PBSS, reduce blood lipid levels, and effectively improve the clinical efficacy of patients.

Risk factors for inpatient malnutrition and length of stay assessed by 'NutritionDay' in China.

BACKGROUND AND OBJECTIVES: NutritionDay is a yearly global point-prevalence study of malnutrition or nutritional risk in hospitals. We aimed to provide a comprehensive nutritional survey of hospitalized patients and analyze the risk factors of malnutrition and prolonged hospitalization in Chinese inpatients. METHODS AND STUDY DESIGN: The international daylong cross-sectional survey was performed on November 07th, 2019. Ten hospitals were invited to participate in this NutritionDay survey. Nutritional risk was identified by nutritional risk screening 2002, and malnutrition was identified by the ESPEN criteria. We measured the incidence of malnutrition and nutritional risk. And we analysed risk factors for malnutrition and length of stay in Chinese hospitalized patients. RESULTS: 875 hospitalized patients from 6 departments were included in the analysis. The malnutrition rate was 11.6% and the incidence of nutritional risk was 17.8%. It was analyzed that tumor load, end-stage disease, motility, self-rated health, types of oral medicine, and food intake during the past week were independent risk factors for malnutrition or nutritional risk. 56.2% (118/210) of patients at nutritional risk or malnutrition received extra nutritional support, whereas 22.5% (88/391) well-nourished patients did. Moreover, nutrition status, ever stayed in ICU and self-rated health were associated with prolonged length of stay. CONCLUSIONS: In a word, the prevalence of malnutrition or nutritional risk was about 29.4%. Patients with malnutrition or nutritional risk had a higher transfer rate, lower rehabilitation rate and longer hospital stays. The attention to malnutrition patients needs to be further strengthened.

Altered Brain Function and Causal Connectivity Induced by Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Disorder.

Objective: Repetitive transcranial magnetic stimulation (rTMS) can effectively improve depression symptoms in patients with major depressive disorder (MDD); however, its mechanism of action remains obscure. This study explored the neuralimaging mechanisms of rTMS in improving depression symptoms in patients with MDD. Methods: In this study, MDD patients with first-episode, drug-naive (n = 29) and healthy controls (n = 33) were enrolled. Depression symptoms before and after rTMS treatment were assessed using the Hamilton Depression Rating Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected both before and after the treatment. Changes in the brain function after the treatment were compared using the following two indices: the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which are sensitive for evaluating spontaneous neuronal activity. The brain region with synchronous changes was selected as the seed point, and the differences in the causal connectivity between the seed point and whole brain before and after rTMS treatment were investigated via Granger causality analysis (GCA). Results: Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus (p < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus (p < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri (p < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus (p < 0.01) and decreased in the left middle frontal gyrus and left precuneus (p < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri (p < 0.01) in patients with MDD. Before treatment, GCA using the left middle frontal gyrus (the brain region with synchronous changes) as the seed point revealed a weak bidirectional causal connectivity between the middle and superior frontal gyri as well as a weak causal connectivity from the inferior temporal to the middle frontal gyri. After treatment, these causal connectivities were strengthened. Moreover, the causal connectivity from the inferior temporal gyrus to the middle frontal gyri negatively correlated with the total HAMD-17 score (r = -0.443, p = 0.021). Conclusion: rTMS treatment not only improves the local neural activity in the middle frontal gyrus, superior frontal gyrus, and precuneus but also strengthens the bidirectional causal connectivity between the middle and superior frontal gyri and the causal connectivity from the inferior temporal to the middle frontal gyri. Changes in these neuroimaging indices may represent the neural mechanisms underlying rTMS treatment in MDD. Clinical Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).

Astrocytic glycogen mobilization participates in salvianolic acid B-mediated neuroprotection against reperfusion injury after ischemic stroke.

Astrocytic glycogen serves as an important glucose reserve, and its degradation provides extra support for neighboring neurons during energy deficiency. Salvianolic acid B (SAB) exerts a neuroprotective effect on reperfusion insult after cerebrovascular occlusion, but the effect of SAB on astrocytic glycogen and its relationship with neuroprotection are not completely understood. Here, we knocked down astrocyte-specific glycogen phosphorylase (GP, the rate-limiting enzyme in glycogenolysis) in vitro and in vivo and investigated the changes in key enzymes in glycogen metabolism by performing immunoblotting in vitro and immunofluorescence in vivo. Neurobehavioral and morphological assessments were conducted to uncover the outcomes during brain reperfusion. SAB accelerated astrocytic glycogenolysis by upregulating GP activity but not GP expression after reperfusion. Suppression of astrocytic glycogenolysis weakened SAB-mediated neuroprotection against the reperfusion insult. In addition, activation of glycogenolysis by SAB contributed to the survival of astrocytes and surrounding neurons by increasing antioxidant levels in astrocytes. Our data reveal that astrocytic GP represents an important metabolic target in SAB-induced protection against brain damage after cerebrovascular recanalization.

Current study on the influence of psychological factors on returning to sports after ACLR.

It is considered that psychological factors are important in determining exercise regression outcomes of patients with anterior cruciate ligament reconstruction (ACLR). This review summarizes the definition and research progress of current undefined psychological factors related to returning to sports (RTS) after ACLR, as well as the application of corresponding measuring scales, and common psychological interventions in the field. The aim is to understand and clarify the impact of psychological factors in the ACL injury and rehabilitation, and to provide a theoretical basis for the application of psychological evaluation and intervention in the later stage. It is believed that there are still many prospects for the research in this field.

Superior Hg0 capture performance and SO2 resistance of Co-Mn binary metal oxide-modified layered MCM-22 zeolite for SO2-containing flue gas.

A Co-Mn binary metal oxide-modified layered MCM-22 zeolite was designed to capture gaseous elemental mercury (Hg0) from SO2-containing flue gas. The physicochemical properties of the Co-Mn/MCM-22 zeolite were characterized by XRD, FESEM, TEM, and XPS, and the results showed that MnO2 was highly dispersed on the surface and in the channel of MCM-22 zeolite. Co3O4 was loaded onto the surface of the MCM-22 zeolite via the stepwise ion exchange method to prevent SO2 poisoning of the MnO2 active site. The Hg0 removal efficiency increased from 54 to 83% at 300 °C with 10% Co loading on the 5% Mn/MCM-22 zeolite when 200 ppm of SO2 was introduced to the flue gas. The mechanism of Hg0 removal was mainly associated with catalytic oxidation and chemisorption. Mn4+ was the main active site for catalytic oxidation of Hg0 to Hg2+, and the surface adsorbed oxygen re-oxidized Mn3+ and combined with Hg2+ to form Hg-O-Mn, in which Mn acted as a bridge. Co3+ preferentially reacted with SO2 to form CoSO4, thereby protecting the Mn active sites for Hg0 capture. Therefore, Co-Mn/MCM-22 zeolite is a promising sorbent for the removal of Hg0 and SO2 resistance from SO2-containing flue gas.

Carbonate and phosphite encaged in frameworks constructed from square lanthanum aminopolycarboxylates and sodium chloride.

Novel additives of lanthanum aminopolycarboxylates with inorganic anions, Na12n[La(edta)L]4n·8nNaCl·4nH2O (1: L = HPO32-; 2: L = CO32-) and K12n[La(cdta)(CO3)]4n·35nH2O (3) (H4edta = ethylenediaminetetraacetic acid; H4cdta = cyclohexanediaminetetraacetic acid), were obtained in alkaline solution. Structural analyses reveal that 1 and 2 are isomorphous and contain interesting square structures. HPO32- (CO32-) was encaged in the constructed tetranuclear frameworks. Tetranuclear lanthanum ethylenediaminetetraacetate was further encaged in superstructures of sodium chloride. 3 has a similar square structure, in which edta is replaced by cdta. All complexes are fully characterized via elemental, FT-IR, NMR, thermogravimetric and structural analyses. Solution 13C NMR spectra show that 1 and 2 dissociate into mononuclear units in water. Interestingly, 2 possesses 3.7 Å diameter holes inside its crystals, which can adsorb a small amount of O2 or CO2 selectively. The amounts of O2 and CO2 adsorbed increase gradually from 0.32 and 0.38 mg g-1 at 0.4 bar to 15.90 and 10.54 mg g-1 at 29.9 bar, respectively.

Single CRD containing lectin from Macrobrachium rosenbergii (MrLec) participates in innate immunity against pathogen infections.

As a type of pattern-recognition proteins, lectins perform important functions in the innate immunity of crustaceans, including prawns. Although several reports showed that C-type lectin domain family (CLEC) importantly functions in host-pathogen interactions, limited research has focused on CLEC in Macrobrachium rosenbergii. In the present study, a new single CRD containing CLEC (designated as MrLec) was reported in freshwater prawns, M. rosenbergii. The full-length cDNA of MrLec consisted of 1027 bp with an open reading frame of 801 bp, which encoded a peptide of 266 amino acid residues. Genomic sequence for MrLec was also obtained from the M. rosenbergii, which contain 4 exons and 3 introns. MrLec was found to contain a single carbohydrate-recognition domain with an EPN motif. MrLec was ubiquitously distributed in various tissues of a normal prawn, particularly in the hepatopancreas and gills. MrLec expression in the gills was significantly upregulated after a challenge with Vibrio parahaemolyticus and downregulated at 24 h after MrLec RNA interference (MrLec-RNAi). The expression levels of some AMPs, including antilipopolysaccharide factor 1 (Alf1) and lysozyme 2 (Lyso2), also markedly decreased after MrLec-RNAi. Recombinant MrLec can agglutinate (Ca(2+)-dependent) and bind both Gram-negative and Gram-positive bacteria. Results suggested that MrLec participates in the recognition of invading pathogens and functions in the immune response of prawn against pathogen infections.

Involvement of Relish gene from Macrobrachium rosenbergii in the expression of anti-microbial peptides.

Relish is an NF-kB transcription factor involved in immune-deficiency (IMD) signal pathway. In this study, a Relish gene (MrRelish) was identified from Macrobrachium rosenbergii. The full length of MrRelish comprises 5072 bp, including a 3510 bp open reading frame encoding a 1169 bp amino acid protein. MrRelish contains a Rel homology domain (RHD), a nucleus localization signal, an IκB-like domain (6 ankyrin repeats), and a death domain. Phylogenetic analysis showed that MrRelish and other Relish from crustaceans belong to one group. MrRelish was expressed in all detected tissues, with the highest expression level in hemocytes and intestines. MrRelish was also upregulated in hepatopancreas at 6 h after Vibrio anguillarum challenge. The over-expression of MrRelish could induce the expression of antimicrobial peptides (AMPs), such as Drosophila Metchnikowin (Mtk), Attacin (Atta), Drosomycin (Drs), and Cecropin (CecA) and shrimp Penaeidin (Pen4). The RNAi of MrRelish in gills showed that the expression of crustin (cru) 2, Cru5, Cru8, lysozyme (Lyso) 1, and Lyso2 was inhibited. However, the expression of anti-lipopolysaccharide factor (ALF) 1 and ALF3 did not change when MrRelish was knocked down. These results indicate that MrRelish may play an important role in innate immune defense against V. anguillarum in M. rosenbergii.

Characterization of a gC1qR from the giant freshwater prawn, Macrobrachium rosenbergii.

gC1qR, as a multicompartmental and a multifunctional protein, plays an important role in innate immunity. In this study, a gC1qR homolog (MrgC1qR) in the giant freshwater prawn, Macrobrachium rosenbergii was identified. MrgC1qR, a 258-amino-acid polypeptide, shares high identities with gC1qR from other species. MrgC1qR gene was expressed in different tissues and was highest expressed in the hepatopancreas. In addition, the MrgC1qR transcript was significantly enhanced after 6 h of white spot syndrome virus (WSSV) infection or post 2 h, 24 h of Vibrio anguillarum challenge compared to appropriate controls. Moreover, recombinant MrgC1qR (rMrgC1qR) had bacterial binding activity, the result also revealed that rMrgC1qR could bind pathogen-associated molecular patterns (PAMPs) such as LPS or PGN, suggesting that MrgC1qRmight function as a pathogen-recognition receptor (PRR). Furthermore, glutathione S-transferase (GST) pull-down assays showed that rMrgC1qR with GST-tag could bind to rMrFicolin1 or rMrFicolin2 with His-tag. Altogether, these results may demonstrate a role for MrgC1qR in innate immunity in the giant freshwater prawns.

Function of a novel C-type lectin with two CRD domains from Macrobrachium rosenbergii in innate immunity.

C-type lectins play crucial roles in innate immunity. In the present study, a novel C-type lectin gene, designated as MrCTL, was identified from Macrobrachium rosenbergii. MrCTL contains 2 carbohydrate-recognition domains (CRDs), namely MrCRD1 and MrCRD2. The MrCRD1 contains a QEP motif and MrCRD2 contains a motif of EPD. MrCTL was mainly expressed in the hepatopancreas. The expression level of MrCTL in hepatopancreas was significantly upregulated after a challenge with Vibrio parahaemolyticus or White spot syndrome virus (WSSV). The recombinant MrCTL, MrCRD1 and MrCRD2 have an ability to agglutinate both Gram-negative (V. parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) in a calcium dependent manner. The recombinant MrCTL, MrCRD1 and MrCRD2 bind directly to all tested microorganisms. All these results suggested that MrCTL may have important roles in immune defense against invading pathogens in prawns.

[A novel method based on Y-shaped cotton-polyester thread microfluidic channel].

A novel method based on Y-shaped microfluidic channel was firstly proposed in this study. The microfluidic channel was made of two cotton-polyester threads based on the capillary effect of cotton-polyester threads for the determination solutions. A special device was developed to fix the Y-shaped microfluidic channel by ourselves, through which the length and the tilt angle of the channel can be adjusted as requested. The spectrophotometry was compared with Scan-Adobe Photoshop software processing method. The former had a lower detection limit while the latter showed advantages in both convenience and fast operations and lower amount of samples. The proposed method was applied to the determination of nitrite. The linear ranges and detection limits are 1.0-70 micromol x L(-1), 0.66 micromol x L(-1) (spectrophotometry) and 50-450 micromol x L(-1), 45.10 micromol x L(-1) (Scan-Adobe Photoshop software processing method) respectively. This method has been successfully used to the determination of nitrite in soil samples and moat water with recoveries between 96.7% and 104%. It was proved that the proposed method was a low-cost, rapid and convenient analytical method with extensive application prospect.

Cloning and characterization of two different ficolins from the giant freshwater prawn Macrobrachium rosenbergii.

Ficolins, a kind of lectin containing collagen-like and fibrinogen-related domains (FReDs, also known as FBG or FREP), are involved in the first line of host defense against pathogens. In this study, two ficolins, namely, MrFico1 and MrFico2, from the giant freshwater prawn Macrobrachium rosenbergii were identified. In contrast to other ficolins, these two ficolins have no collagen-like domain, but such ficolins contain a coiled region and a FReD domain. Phylogenetic analysis showed that MrFico1 and MrFico2, together with two ficolin-like proteins from Pacifastacus leniusculus, belonged to one group. Quantitative RT-PCR (qRT-PCR) showed that both MrFico1 and MrFico2 were expressed in hepatopancreas, stomach and intestine, with the highest expression in stomach for MrFico1, compared to the highest expression in hepatopancreas for MrFico2. qRT-PCR analysis also showed that MrFico1 was obviously upregulated upon Vibrio anguillarium challenge, while MrFico2 was upregulated after challenged by V. anguillarium or white spot syndrome virus. Bacterium-binding experiment showed that MrFico1 and MrFico2 could bind to different microbes, and sugar-binding assay revealed that these two ficolins could also bind to lipopolysaccharide and peptidoglycan, the glycoconjugates of bacteria surface. Moreover, these two ficolins could agglutinate bacteria in a calcium-dependent manner, and the results of bacteria clearance experiment showed that both ficolins could facilitate the clearance of injected bacteria in the prawn. Our results suggested that MrFico1 and MrFico2 may function as pattern-recognition receptors in the immune system of M. rosenbergii.

Identification and function of two myeloid differentiation factor 88 variants in triangle-shell pearl mussel (Hyriopsis cumingii).

Myeloid differentiation factor 88 (MyD88) is a universal and essential adapter protein that participates in the activation of the Toll-like receptor (TLR)/interleukin-1 receptor-mediated signaling pathway. In this study, two MyD88 genes (HcMyD88-1 and HcMyD88-2) were identified from triangle-shell pearl mussel (Hyriopsis cumingii). Both HcMyD88-1 and HcMyD88-2 proteins were determined to have a death domain at the N-terminal and a TIR domain at the C-terminal. Both HcMyD88-1 and HcMyD88-2 genes were mainly expressed in the hepatopancreas of healthy mussels. HcMyD88-1 and HcMyD88-2 slightly responded to Gram-negative bacterial challenge. Upon bacterial challenge with Gram-positive Staphyloccocus aureus, HcMyD88-1 and HcMyD88-2 transcription levels remarkably increased at 2 and 6h, respectively. Overexpression of HcMyD88-1 and HcMyD88-2 proteins in Drosophila Schneider 2 cells led to the activation of antimicrobial peptide genes. These results indicated that HcMyD88-2 had higher activity than HcMyD88-1 during the activation of attacin A, drosomycin, and metchnikowin genes, suggesting that HcMyD88 genes may play a role in antibacterial innate immune defense.

Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway.

Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8mg/kg for mice or 20µmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals.

Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO.

Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect. However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear. To explore the potential mechanism, herein, ethanol (4.0 g/kg.bw.) was administrated to rats for 90 days. Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.). Quercetin (100 µM) induced HO-1 and depleted heme pool when incubated to human hepatocytes. Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation. CO scavenging blocked the suppression of quercetin only on CYP2E1 activity. CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger. Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction. Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively.

Bilirubin participates in protecting of heme oxygenase-1 induction by quercetin against ethanol hepatotoxicity in cultured rat hepatocytes.

To attenuate alcohol liver disease (ALD) is extremely urgent since ALD has been emerged as a major liver disease. The aim of the present study is to investigate the hepatoprotective effect against ethanol-induced injury of bilirubin, a product of heme metabolism degradation via HO and biliverdin reductase catalysis. Ethanol-incubated primary rat hepatocytes (100 mmol/L) were treated by quercetin, bilirubin, inflammatory factors, and/or HO-1 inducer/inhibitor for 24 h, and the cellular damage was assayed. Quercetin lowered ethanol-induced glutathione depletion and superoxide dismutase inactivation, inhibited the overproduction of malondialdehyde and reactive oxygen species, and decreased the leakage of cellular aspartate aminotransferase and lactate dehydrogenase, accompanying the normalization of bilirubin level. The effect of quercetin was mimicked by exogenous bilirubin in a dose-dependent manner to some extent (within 25 µmol/L) and pharmacological HO-1 inducer hemin, but abolished by HO-1 inhibitor zinc protoporphyrin-IX. Inflammatory challenge of TNF-α plus IL-6 further aggravated ethanol-induced oxidative damage, which was also attenuated by bilirubin in part. These findings shed a light on the anti-oxidative and anti-inflammatory role of bilirubin released from quercetin/HO-1 and biliverdin reductase pathway against ethanol hepatotoxicity and highlight a prospective strategy of nutritional intervention for ALD by naturally occurring quercetin to induce HO-1 with the release of bioactive end-products.