Morphology and optical properties of Au-Ag hybrid nanoparticles regulation and its ultra-sensitive SERS immunoassay detection in carbohydrate antigen 19-9.

The development of an ultra-sensitive detection method for carbohydrate antigen 19-9 (CA19-9) is very important for the early diagnosis of pancreatic cancer. In this work, we developed a new strategy to achieve a variety of Au-Ag hybrid nanoparticles from janus to core-satellite which is controlled by the volume of AgNO3 and the concentration of benzimidazolecarboxylic acid (MBIA). With the volume of AgNO3 increased, Au-Ag hybrid nanoparticles changed from janus to core-satellite and the characteristic absorption peak showed two opposite trends. The size and number of Ag islands were determined by the concentration of MBIA. Au-Ag core-satellites nanoparticles with a large number of small-sized Ag have the highest SERS intensity. Then we used them as SERS nanotags and Au-Polystyrene nanospheres modified by captured anti-CA19-9 antibody as solid substrates to realize the ultra-sensitive detection of CA19-9 with a low limit of detection of 1.25 × 10-6 IU/mL and a wide linear range of 1.00 × 10-5 -1.00 × 104 IU/mL. This work not only demonstrates that MBIA and AgNO3 were the key factors in the growth of Au-Ag hybrid nanoparticles from 2D to 3D structure but also supplies an ultra-sensitive detection method for CA19-9 which has a potential practicability in the clinical early diagnoses of pancreatic cancer.

Taurine Prevents AFB1-Induced Renal Injury by Inhibiting Oxidative Stress and Apoptosis.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins, which can cause serious kidney damage after ingestion. Taurine protects the kidney, an effect related to its antioxidation and anti-apoptotic actions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine on AFB1-induced renal injury in rats. The results show that taurine ameliorated the increase in serum blood urea nitrogen (BUN), blood creatinine (CRE), blood uric acid (UA), cystatin c (Cys-c), and urinary protein and AKP levels. Taurine also inhibits the content of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), succinate dehydrogenase (SDH), and the mRNA expression of SOD, nicotinamide adenine dinucleotide phosphate-quinine oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and glutamate cysteine ligase catalytic (GCLC) in rat kidney tissue. The apoptotic rate of renal cells was decreased by taurine through inhibition of a mitochondrial mechanism. In summary, we found that taurine prevents AFB1-induced renal injury via enhanced antioxidant ability and mitochondrial-dependent apoptosis.

Taurine attenuates AFB1-induced liver injury by alleviating oxidative stress and regulating mitochondria-mediated apoptosis.

Aflatoxin B1 (AFB1), which widely exists in soil and crops, is the most toxic aflatoxin and a carcinogen to humans and animals. The liver is the main organ that processes AFB1 and other mycotoxins and is also the main target of AFB1 toxicity. Taurine is known to exhibit a variety of physiological and pharmacological functions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine in AFB1-induced liver injury in rats. The results showed that taurine inhibited the increase in hepatic injury indices, hepatic apoptosis and hepatic malondialdehyde (MDA) contents while significantly enhanced the hepatic activities of antioxidant enzymes and mitochondrial function-related indices in AFB1-poisoned rats. Meanwhile, the expression levels of key factors in the Nrf2 signalling pathway were upregulated while the expression levels of key proteins in the mitochondria-mediated apoptotic pathway were downregulated after taurine administration. The results showed that taurine can reverse AFB1-induced liver injury and abnormal apoptosis through activation of the Nrf2 signalling pathway and its downstream antioxidant enzymes, which further protects mitochondria from oxidative stress and the subsequent apoptotic pathway.

Global leadership initiative in malnutrition (GLIM) criteria using hand-grip strength adequately predicts postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer.

BACKGROUND: The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI). METHODS: Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS. RESULTS: A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P < 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P < 0.001, both), and disease-free survival (P < 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications. CONCLUSIONS: GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.

The relationship between the GLIM-defined malnutrition, body composition and functional parameters, and clinical outcomes in elderly patients undergoing radical gastrectomy for gastric cancer.

OBJECTIVE: The present study aims to determine the correlations between Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition and body composition and functional parameters, and to comprehensively analyze the predictive value of GLIM-defined malnutrition for postoperative outcomes in the context of detailed measurement of body composition and functional parameters in elderly patients who underwent radical gastrectomy for gastric cancer. METHODS: Elderly patients (aged ≥65 years) who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index (SMI), skeletal muscle density (SMD), subcutaneous fat area (SFA), and visceral fat area (VFA) were analyzed using abdominal computed tomography (CT) images. Handgrip strength and 6-m gait speed were measured. RESULTS: A total of 597 elderly patients were included in this study, in which 45.7% were at risk of malnutrition identified using Nutritional Risk Screening 2002 (NRS 2002), and 34.5% were diagnosed with malnutrition. Patients with malnutrition had lower SMI, SMD, SFA, VFA, lower handgrip strength and gait speed. Low handgrip strength and age ≥80 years were independent risk factors for postoperative complications, rather than GLIM-defined malnutrition. GLIM-defined malnutrition was independently associated with overall survival and disease-free survival after adjusting to the body composition and functional parameters in the multivariate analyses. CONCLUSIONS: GLIM-defined malnutrition was a better predictive factor than single parameters of body composition or physical function for survival in elderly gastric cancer patients. Handgrip strength can be used as a supportive measure to further improve the definition of malnutrition.

Value of muscle quality, strength and gait speed in supporting the predictive power of GLIM-defined malnutrition for postoperative outcomes in overweight patients with gastric cancer.

BACKGROUND: The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes. METHODS: Overweight patients (body mass index (BMI) ≥23 kg/m2) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery. RESULTS: A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m2). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis. CONCLUSION: Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols.

Hypoxic preconditioning combined with curcumin promotes cell survival and mitochondrial quality of bone marrow mesenchymal stem cells, and accelerates cutaneous wound healing via PGC-1α/SIRT3/HIF-1α signaling.

Restrained survival and function of relocated bone marrow mesenchymal stem cells (BMSCs) is a major impediment to BMSCs-mediated tissue repair. Accumulating evidences have indicated that hypoxic preconditioning of BMSCs could enhance BMSCs' adaptability after transplantation and thus improve their therapeutic properties. Curcumin, a natural dietary product, is known to exert profound protective effects on various cellular processes. Here we showed that mild hypoxic preconditioning combined with curcumin significantly increased cell survival, enriched more cells in G2/M and S phase, and improved mitochondrial function in BMSCs. Meanwhile, hypoxic preconditioning combined with curcumin altered mitochondrial cristae shape and strongly inhibited mitochondrial cytochrome c release, which consequently suppressed an apoptosis signal as revealed by reduced caspase-3 cleavage in BMSCs. Moreover, hypoxic preconditioning remarkably promoted mitochondrial quality via increasing mitochondrial fusion and elevating the activity of oxidative phosphorylation (OXPHOS) and mitochondrial complex Ⅰ enzyme in BMSCs, which were in accordance with the up-regulated expression of OPA1, PINK1 and Parkin. At the mechanistic level, the destabilization of HIF-1α and the up-regulated expression of PGC-1α and SIRT3 synergistically contributed to the protective effects of hypoxic preconditioning combined with curcumin in BMSCs. The proteasome inhibitor MG132 stabilized HIF-1a expression, but not PGC-1α or SIRT3, and dramatically restrained BMSCs survival under hypoxia combined with curcumin condition. MG132 also increased mitochondrial superoxide and intracellular hydrogen peroxide (H2O2) production and caspase-3 activation in hypoxia combined with curcumin-treated BMSCs. Furthermore, knockdown of SIRT3 and PGC-1α by RNAi both led to caspase-3 activation in BMSCs after hypoxia and curcumin treatment. Notably, SIRT3 RNAi suppressed OXPHOS activity, while PGC-1α RNAi triggered mitochondrial superoxide and intracellular H2O2 production in hypoxia combined with curcumin-treated BMSCs. Finally, we showed that hypoxia combined with curcumin-treated BMSCs accelerated the cutaneous wound healing process in a mice wound model. Overall, this study suggests that hypoxic preconditioning combined with curcumin could serve as an attractive strategy for facilitating BMSCs-mediated tissue repair, and further sheds new light on the rich repertoire of PGC-1α/SIRT3/HIF-1α signaling involved in the regulation of mitochondrial quality and function for cellular adaption to hypoxia.

Burn-Induced Apoptosis of Pulmonary Microvascular Endothelial Cell is NHE1 Dependent and Regulated by PI3K-Akt and p38 MAPK Pathways.

Na/H exchanger 1 (NHE1) is a ubiquitously expressed protein on mammalian plasma membranes and involved in cell apoptosis and tissue injury. Our previous study found that NHE1 inhibition prevents burn-induced acute lung injury (ALI). However, the potential mechanism of NHE1 in burn-induced ALI is still unclear. This study investigated the role of NHE1 in burn-induced apoptosis of human pulmonary microvascular endothelial cells. Based on the western blot analyses, real-time PCR, fluorescence spectroscopy, and apoptosis analysis, we found that burn serum significantly induced NHE1 activation, promoted intracellular Na accumulation, and elevated apoptosis ratio. Inhibition of NHE1 with cariporide reversed burn-induced intracellular Na accumulation and cell apoptosis. Different doses of cariporide also significantly decreased Cai concentrations and calpain activity induced by burn serum. Furthermore, inhibition of PI3K contributed to the increase of NHE1 activation and cell apoptosis, whereas the inhibition of p38 MAPK led to inhibition of NHE1 activation and significant decreases of cell apoptosis. The data demonstrate that NHE1 activation facilitates burn-induced endothelial cell apoptosis, mediated by Ca-dependent pathway. PI3K-Akt and p38 MAPK were found to be upstream regulators of NHE1. This study provides new mechanisms underlying burn-induced ALI.

Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT.

Hypertrophic scar (HS) is a serious fibrotic skin disease and often considered as a kind of benign skin tumor. Tetramethylpyrazine (TMP), the main chemical composition of the traditional Chinese medicine Chuanxiong Rhizoma, has shown significant clinical benefits in the treatment of fibrosis disease and tumor, while the role in HS and the concrete mechanisms remain elusive. Herein, the protective effects of TMP in the treatment of HS was investigated and the results showed that the protein expression levels of type I collagen (Col I), type III collagen (Col III), and α-smooth muscle actin (α-SMA) were all inhibited remarkably after addition of TMP in HS-derived fibroblasts (HFs). Moreover, TMP also suppressed fibroblast proliferative and induced cell apoptosis. The protein expression levels of Caspase-3 and Bcl-2 were all decreased comparing with the control group while proapoptotic proteins Bax and Cleaved Caspase-3 were increased. In addition, TMP treatment markedly reduced the phosphorylation levels of AKT. Taken together, our investigations demonstrated that TMP could down-regulate the expression of fibrosis-related molecules, inhibit scar fibroblast proliferation and activate cell apoptosis, during which AKT pathway was involved. Thus, this study shed more light on the pharmacological mechanisms of TMP, and provided a novel therapeutic alternative for prevention and treatment of HS.

Taurine attenuates isoproterenol-induced H9c2 cardiomyocytes hypertrophy by improving antioxidative ability and inhibiting calpain-1-mediated apoptosis.

Pathological cardiac hypertrophy is ultimately accompanied by cardiomyocyte apoptosis. Apoptosis mainly related to calpain-1-mediated apoptotic pathways. Studies had proved that taurine can maintain heart health through antioxidation and antiapoptotic functions, but the effect of taurine on cardiac hypertrophy is still unclear. This study aimed to determine whether taurine could inhibit calpain-1-mediated mitochondria-dependent apoptotic pathways in isoproterenol (ISO)-induced hypertrophic cardiomyocytes. We found that taurine could inhibit the increase in cell surface area and reduce the protein expression levels of the hypertrophic markers atrial natriuretic peptide, brain natriuretic polypeptide, and ß-myosin heavy chain. Taurine also reduced ROS, intracellular Ca2+ overload and mitochondrial membrane potential. Moreover, taurine inhibited cardiomyocyte apoptosis by decreasing the protein expression of calpain-1, Bax, t-Bid, cytosolic cytochrome c, Apaf-1, cleaved caspase-9 and cleaved caspase-3 and by enhancing calpastatin and Bcl-2 protein expression. Calpain-1 small interfering RNA transfection results showed similar antiapoptotic effects as the taurine prevention group. However, compared with the two treatments, taurine inhibited the expression of cleaved caspase-9 more significantly. Therefore, we believe that taurine prevents ISO-induced H9c2 cardiomyocyte hypertrophy by inhibiting oxidative stress, intracellular Ca2+ overload, the calpain-1-mediated mitochondria-dependent apoptotic pathway and cleaved caspase-9 levels.

ING4 alleviated lipopolysaccharide-induced inflammation by regulating the NF-κB pathway via a direct interaction with SIRT1.

Sepsis is a complex inflammatory disorder in which high mortality is associated with an excessive inflammatory response. Inhibitor of growth 4 (ING4), which is a cofactor of histone acetyltransferase and histone deacetylase complexes, could negatively regulate this inflammation. However, the exact molecular signaling pathway regulated by ING4 remains uncertain. As a pivotal histone deacetylase, Sirtuin1 (SIRT1), which is widely accepted to be an anti-inflammatory molecule, has not been found to be linked to ING4. This study investigated how ING4 is involved in the regulation of inflammation by constructing lipopolysaccharide (LPS)-induced macrophage and mouse sepsis models. Our results revealed that ING4 expression decreased, whereas the levels of proinflammatory cytokines increased in LPS-stimulated cultured primary macrophages and RAW 264.7 cells. ING4 transfection was confirmed to alleviate the LPS-induced upregulation of proinflammatory cytokine expression both in vitro and in vivo. In addition, ING4-overexpressing mice were hyposensitive to an LPS challenge and displayed reduced organ injury. Furthermore, immunoprecipitation indicated a direct interaction between ING4 and the SIRT1 protein. Moreover, ING4 could block nuclear factor-kappa B (NF-κB) P65 nuclear translocation and restrict P65 acetylation at lysine 310 induced by LPS treatment. These results are the first to clarify that the anti-inflammatory role of ING4 is associated with SIRT1, through which ING4 inhibits NF-κB signaling activation. Our studies provide a novel signaling axis involving ING4/SIRT1/NF-κB in LPS-induced sepsis.

Taurine Inhibited Uric Acid Uptake in HK-2 Renal Tubular Epithelial Cells.

It has been confirmed by our laboratory that taurine could decrease uric acid levels in hyperuricemic rats and regulate the expressions of some urate transporters. The present study aims to investigate the effects of taurine on uric acid uptake in human renal proximal tubular epithelial cells (HK-2). The cell growth inhibition rate was measured by MTS assay, which was up to 50% after treatment with 1.5 mmol/L uric acid. After administration of 15 mmol/L taurine, the inhibition rate and uric acid uptake were both significantly decreased. Then the HK-2 cells were grouped as follows: control group (C); model group (M), in which 1.5 mmol/L uric acid was added to the medium; taurine group (MT), in which 1.5 mmol/L uric acid and 15 mmol/L taurine were added to the medium; and taurine control group (T), in which 15 mmol/L taurine was added to the medium. The mRNA and protein expression levels of URAT1 and GLUT9 were measured by real-time PCR and western-blot. The results showed that URAT1 and GLUT9 mRNA/protein expression levels in group M were significantly increased compared with group C, and they were both down-regulated in MT group. In addition, the expression levels of these two transporters in group T were significantly lower than group C. The results indicated that taurine could inhibit uric acid uptake and down-regulate the expressions of URAT1 and GLUT9 in HK-2 cells.

The use of autologous platelet-rich plasma gel increases wound healing and reduces scar development in split-thickness skin graft donor sites.

The treatment of donor sites after split-thickness skin grafting (STSG) is a routine operation step, and complications at the donor site due to improper operation and care are unwelcome. This study evaluates whether the use of platelet-rich plasma (PRP) applied at the STSG area promotes wound healing and improves scar development. Clinical data of 30 patients who underwent STSG operations between January 2016 and January 2017 for various reasons were retrospectively analyzed. These 30 patients received two treatments and the data were summed up in two groups: the PRP group, which was the study group, included patients who received traditional petrolatum gauze dressing with PRP gel at the donor sites. The petrolatum gauze group, which was the control group, received only petrolatum gauze care without PRP gel. The time and frequency of dressing change were comparable between the two groups, and the mean wound healing times in the PRP group and petrolatum gauze group were 13.89 ± 4.65 and 17.73 ± 5.06 days, respectively, and the difference was statistically significant (p < 0.05). In addition, the total Vancouver scar scale (VSS) scores of the PRP group at 4, 12 and 52 weeks were 6.41 ± 0.77, 4.42 ± 0.43 and 2.41 ± 0.39, respectively, which were statistically significantly lower (p < 0.05) than those of the control group at 7.67 ± 0.64, 6.28 ± 0.62 and 4.29 ± 0.64, respectively. The use of PRP gel can promote wound healing, relieve scar development and alleviate pain at the donor site after STSG.

The Akt/FoxO/p27Kip1 axis contributes to the anti-proliferation of pentoxifylline in hypertrophic scars.

Hypertrophic scars (HS) are characterized by the excessive production and deposition of extracellular matrix (ECM) proteins. Pentoxifylline (PTX), a xanthine derived antioxidant, inhibits the proliferation, inflammation and ECM accumulation of HS. In this study, we aimed to explore the effect of PTX on HS and further clarify the mechanism of PTX-induced anti-proliferation. We found that PTX could significantly attenuate proliferation of HS fibroblasts and fibrosis in an animal HS model. PTX inhibited the proliferation of HSFs in a dose- and time-dependent manner, and this growth inhibition was mainly mediated by cell cycle arrest. Transcriptome sequencing showed that PTX affects HS formation through the PI3K/Akt/FoxO1 signalling pathway to activate p27Kip1 . PTX down-regulated p-Akt and up-regulated p-FoxO1 in TGF-ß1 stimulated fibroblasts at the protein level, and simultaneously, the expression of p27Kip1 was activated. In a mouse model of HS, PTX treatment resulted in the ordering of collagen fibres. The results revealed that PTX regulates TGFß1-induced fibroblast activation and inhibits excessive scar formation. Therefore, PTX is a promising agent for the treatment of HS formation.

ROR alpha protects against LPS-induced inflammation by down-regulating SIRT1/NF-kappa B pathway.

Systemic inflammatory response syndrome (SIRS) is associated with excessive inflammatory response, however, the pathophysiology of inflammation is poorly understood. The retinoid-related orphan receptor α (RORα) is a key inflammatory regulator, but the mechanisms underlying its role remain unclear. The aim of this study was to investigate how RORα was involved in the regulation of inflammatory response. Here we put forward a hypothesis that RORα might negatively regulate inflammatory response by controlling silent information regulator Sirtuin 1 (SIRT1) expression. Stimulation of macrophages in vitro with LPS and LPS administration in vivo were used to explore the function of RORα and the relationship between RORα and SIRT1. We found that the level of RORα was suppressed in macrophages stimulated with LPS and overexpression or knockdown of RORα by transfection with lentivirus or siRNAs significantly decreased or increased, respectively, the pro-inflammatory cytokines IL-1ß, TNF, IL-6 and MCP-1. Importantly, overexpression of RORα suppressed inflammation and alleviated LPS-induced organ injury in vivo. Further study showed that RORα could regulate SIRT1 expression and, consequently, affect deacetyation and nuclear translocation of nuclear factor-kappa B (NF-κB) subunit p65. Moreover, the activation of SIRT1 by its specific agonist, SR1720, could reduce the expression of proinflammatory cytokines in RORα knockdown macrophages stimulated with LPS. In conclusion, we demonstrated that RORα could alleviate LPS-induced inflammation and organ injury both in vivo and in vitro by blocking NF-κB p65 nuclear translocation and restricting acetylation of NF-κB p65 at lysine 310 via the regulation of SIRT1 expression. Targeting RORα might be a promising therapeutic strategy to regulate inflammatory disorders.

MCPIP1 alleviated lipopolysaccharide-induced liver injury by regulating SIRT1 via modulation of microRNA-9.

The severity of sepsis is associated with excessive inflammatory responses. MCP-1 induced protein (MCPIP1) could negatively regulate inflammatory responses by deubiquitinating K48 or K63 polyubiquitins of TNF receptor-associated factors. The function of MCPIP1 in negative regulation of inflammation is known, however, only the exact molecular pathway remains unknown. The aim of this study was to investigate whether and how MCPIP1 is involved in the regulation of lipopolysaccharides (LPS)-induced liver injury. Macrophages and a mouse model were induced by LPS treatment. Several in vitro assays, such as quantitative real-time PCR, immunoblotting, cell transfection, dual luciferase reporter assay, Enzyme-linked immunosorbent assay, and Hematoxylin-Eosin staining assay were used to explore the role of MCPIP1 and the interaction between MCPIP1, Sirtuin 1 (SIRT1), and microRNA-9 (miR-9). We found that the level of MCPIP1 increased and the level of SIRT1 decreased in LPS induced Kupffer cells or RAW 264.7 macrophages. Overexpression of MCPIP1 alleviated cytokine secretion and p65 nuclear translocation. Further study showed that MCPIP1 regulated p65 nuclear translocation by controlling p65 acetylation via promoting SIRT1 expression. Meanwhile, we found that miR-9 could directly regulate SIRT1 transcription by binding to the 3'-Untranslated Region of SIRT1 messenger RNA and that miR-9 was negatively regulated by MCPIP1. Importantly, overexpression of MCPIP1 in vivo could alleviate LPS-induced inflammation responses and liver injury in septic mice. These results demonstrated that MCPIP1 could alleviate inflammation responses and sepsis associated liver injury by promoting the expression of SIRT1, and miR-9 was involved in the MCPIP1-mediated regulation of SIRT1. Collectively, our results provide a possible novel signaling axis involving MCPIP1/miR-9/SIRT1 in LPS-induced septic mice.

Taurine Inhibits Kupffer Cells Activation Induced by Lipopolysaccharide in Alcoholic Liver Damaged Rats.

Taurine, a ß free amino-acid, takes various biological functions including maintain the normal hepatic structure and function. In this study, the regulation mechanism of taurine on lipopolysaccharide (LPS) induced activation of Kupffer cells (KC) in the liver of rats with alcoholic liver disease (ALD) were explored. Male wistar rats were intragastrically administered with alcohol and pyrazole, and ate high-fat diet in order to establish ALD model. Taurine were administered in drinking water simultaneous with and after ALD model establishment. The preventive trial was lasted for 12 weeks, while the curative trial was lasted for 4 weeks. Finally, blood and liver were collected in order to detect the concentrations of plasma LPS and hepatic tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Hepatic total RNA were extracted, gene expressions of LPS binding protein (LBP), leukocyte differentiation antigen 14 (CD14), toll-like receptors (TLR4), nuclear transcription factor (NF-κB) and TNF-α were detected by semi-quantitative RT-PCR. The results showed significant elevated levels of plasma LPS, hepatic TNF-α, IL-1ß and IL-6 in ALD rats (P < 0.05), and heightened gene expressions of LBP, CD14, TLR4, NF-κB and TNF-α (P < 0.05); Taurine no matter administered preventively or curatively can reduce the levels of plasma LPS, hepatic TNF-α, IL-1ß, IL-6, and down-regulate the gene expressions of LBP, CD14, TLR4, NF-κB and TNF-α. The results demonstrated that taurine can prevent and cure ALD by reducing the production and transformation of LPS as well as inhibiting the opening and the transmission of LPS induced KC activation and the downstream signaling pathway.

Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats.

Depression, a psychiatric and dysthymic disorder, severely affects the learning, work and life quality. The main pathogenesis of depression is associated with central nervous system (CNS) dysfunction. Taurine has been demonstrated to exert protective effects on the brain development and can improve learning ability and memory. Our study investigated the antidepressant-like effects of taurine pre-treatment by examining the changes in depression-like behavior, hormones, neurotransmitters, inflammatory factors and neurotrophic factors in the hippocampus of a chronic unpredictable mild stress (CUMS)-induced depressive rat model. Taurine was found to inhibit the decrease of sucrose consumption and prevent the deficiency of spatial memory and anxiety in rats exposed to CUMS, suggesting a preventive effect of taurine on depression-like behavior. Furthermore, the decreased levels of 5-hydroxytryptamine, dopamine, noradrenaline; the increased levels of glutamate, corticosterone; and the decreased expressions of fibroblast growth factor-2, vascular endothelial growth factor and brain derived neurotrophic factor in depressive rats were hindered by taurine pre-administration. However, tumor necrosis factor-α and interleukin-1ß levels were not significantly changed by taurine. The results demonstrated that the anti-depressive effect of taurine may be involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and the promotion of neurogenesis, neuronal survival and growth in the hippocampus.

Chromate Reductase YieF from Escherichia coli Enhances Hexavalent Chromium Resistance of Human HepG2 Cells.

Hexavalent chromium (Cr(VI)) is a serious environmental pollutant and human toxicant. Mammalian cells are very sensitive to chromate as they lack efficient chromate detoxifying strategy, e.g., chromate-reducing genes that are widely present in prokaryotes. To test whether introduction of prokaryotic chromate-reducing gene into mammalian cells could render higher chromate resistance, an Escherichia coli chromate-reducing gene yieF was transfected into human HepG2 cells. The expression of yieF was measured in stably transfected cells HepG2-YieF by quantitative RT-PCR and found up-regulated by 3.89-fold upon Cr(VI) induction. In chromate-reducing ability test, HepG2-YieF cells that harbored the reductase showed significantly higher reducing ability of Cr(VI) than HepG2 control cells. This result was further supported by the evidence of increased Cr(VI)-removing ability of crude cell extract of HepG2-YieF. Moreover, HepG2-YieF demonstrated 10% higher viability and decreased expression of GSH synthesizing enzymes under Cr(VI) stress. Subcellular localization of YieF was determined by tracing GFP-YieF fusion protein that was detected in both nucleus and cytoplasm by laser confocal microscopy. Altogether, this study successfully demonstrated that the expression of a prokaryotic Cr(VI)-reducing gene yieF endowed mammalian cell HepG2 with enhanced chromate resistance, which brought new insight of Cr(VI) detoxification in mammalian cells.