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  • Hindawi Limited  (23)
  • 1
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2016 ( 2016), p. 1-14
    Abstract: Objective . Shikonin possesses anti-inflammatory effects. However, its function in concanavalin A-induced acute liver injury remains uncertain. The aim of the present study was to investigate the functions of shikonin and its mechanism of protection on ConA-induced acute liver injury. Materials and Methods . Balb/C mice were exposed to ConA (20 mg/kg) via tail vein injection to establish acute liver injury; shikonin (7.5 mg/kg and 12.5 mg/kg) was intraperitoneally administered 2 h before the ConA injection. The serum liver enzyme levels and the inflammatory cytokine levels were determined at 3, 6, and 24 h after ConA injection. Results . After the injection of ConA, inflammatory cytokines IL-1 β , TNF- α , and IFN- γ were significantly increased. Shikonin significantly ameliorated liver injury and histopathological changes and suppressed the release of inflammatory cytokines. The expressions of Bcl-2 and Bax were markedly affected by shikonin pretreatment. LC3, Beclin-1, and p-JNK expression levels were decreased in the shikonin-pretreated groups compared with the ConA-treated groups. Shikonin attenuated ConA-induced liver injury by reducing apoptosis and autophagy through the inhibition of the JNK pathway. Conclusion . Our results indicated that shikonin pretreatment attenuates ConA-induced acute liver injury by inhibiting apoptosis and autophagy through the suppression of the JNK pathway.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2008065-7
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  • 2
    In: Gastroenterology Research and Practice, Hindawi Limited, Vol. 2016 ( 2016), p. 1-13
    Abstract: Aims. To investigate cerebral hemodynamics in cirrhotic patients with HE and to observe effects of treatment in cerebral hemodynamics and correlations among ammonia, cerebral hemodynamics, and cognitive function. Methods . There were four groups: healthy controls (group 1), cirrhosis without HE (group 2), cirrhosis with MHE (group 3), and cirrhosis with OHE (group 4). Ammonia and cerebral hemodynamics (by TCD) were assessed. Patients in group 3 were subsequently randomized to two subgroups: the control (group A) and the treated (group B, treated with lactulose for two months), and they were retested for ammonia and TCD after treatment. Results. Ammonia, V m , V d , PI, and RI were statistically different before treatment, and ammonia, PI, and RI levels paralleled the severity of HE ( P 〈 0.05 ). In group B, V d increased and ammonia, PI, and RI declined following treatment ( P 〈 0.05 ), while there were no differences in group A ( P 〉 0.05 ). Correlations were found between ammonia and V d , PI, RI, NCT-A, and DST and also found between V d , PI, RI, and NCT-A and DST ( P 〈 0.05 ). Conclusions . This study revealed that cerebral hemodynamics were related to the severity of HE and cerebral autoregulation was impaired. There were tight correlations among ammonia, cerebral hemodynamics, and cognitive function, and, following treatment, cerebral hemodynamics improved.
    Type of Medium: Online Resource
    ISSN: 1687-6121 , 1687-630X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2435460-0
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  • 3
    In: Gastroenterology Research and Practice, Hindawi Limited, Vol. 2017 ( 2017), p. 1-11
    Abstract: Objective . The present study was conducted to compare the efficacy of metformin combined with diammonium glycyrrhizinate enteric-coated capsule (DGEC) versus metformin alone versus DGEC alone for the treatment of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Subjects and Methods . 163 patients with NAFLD and T2DM were enrolled in this 24-week study and were randomized to one of three groups: group 1 was treated with metformin alone; group 2 was treated with DGEC alone; group 3 received metformin plus DGEC combination therapy. Anthropometric parameters, liver function, lipid profile, serum ferritin (SF), metabolic parameters, liver/spleen computed tomography (CT) ratio, and fibroscan value were evaluated at baseline and after 8, 16, and 24 weeks of treatment. Results . After 24 weeks, significant improvements in all measured parameters were observed in three groups ( P 〈 0.05 ) except for the improvements in low density lipoprotein cholesterol (LDL-C) and metabolic parameters in group 2 which did not reach statistical significance ( P 〉 0.05 ). Compared with group 1 and group 2, the patients in group 3 had greater reductions in observed parameters apart from CB and TB ( P 〈 0.05 ). Conclusions . This study showed that metformin plus DGEC was more effective than metformin alone or DGEC alone in reducing liver enzymes, lipid levels, and metabolic parameters and ameliorating the degree of hepatic fibrosis in patients with NAFLD and T2DM.
    Type of Medium: Online Resource
    ISSN: 1687-6121 , 1687-630X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2435460-0
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  • 4
    In: Gastroenterology Research and Practice, Hindawi Limited, Vol. 2017 ( 2017), p. 1-15
    Abstract: Background . Hepatic ischemia reperfusion (IR) injury is a common phenomenon in transplantation or trauma. The aim of the present study was to determine the protective effect of quercetin (QE) on hepatic IR injury via the ERK/NF- κ B pathway. Methods . Mice were randomized into the sham, IR, QE100 + IR, and QE200 + IR groups. Quercetin was administered intragastrically daily at two doses (100 mg/kg and 200 mg/kg) for 5 days prior to IR injury. The expression levels of liver enzymes, inflammatory cytokines, and other marker proteins were determined at 2, 8, and 24 hours after IR. And they were compared among these groups. Results . Compared with the IR group, the treatment of QE reduced the release of cytokines, leading to inhibition of apoptosis and autophagy via downregulation of the ERK/NF- κ B pathway in this model of hepatic IR injury. Conclusion . Apoptosis and autophagy caused by hepatic IR injury were inhibited by QE following a reduction in the release of inflammatory cytokines, and the relationship between the two may be associated with inactivation of the ERK/NF- κ B pathway.
    Type of Medium: Online Resource
    ISSN: 1687-6121 , 1687-630X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2435460-0
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  • 5
    In: Journal of Clinical Pharmacy and Therapeutics, Hindawi Limited, Vol. 2023 ( 2023-7-27), p. 1-10
    Abstract: Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study predicted the influence of NUDT15 haplotypes and diplotypes on azathioprine (AZA)-induced leukopenia as well as the long-term influence of AZA on hematologic parameters in IBD. Methods. 194 IBD patients were tested for NUDT15 genotypes. We collected clinical data of 80 patients with AZA treatment including adverse events, dosage, white blood cell (WBC) count, platelet (PLT) count, and mean corpuscular volume (MCV) after AZA initiation. Patients without adverse events and drug withdrawal were followed up for at least one year. The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C  〉  T and c.36_37insGGAGTC as well as the diplotypes NUDT15 ∗ 1/ ∗ 2, ∗ 3/ ∗ 3, and ∗ 3/ ∗ 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G  〉  A experienced leukopenia. NUDT15 ∗ 1/ ∗ 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group ( P = 0.006 ). The MCV increased gradually in mutant cases ( P = 0.039 ), and the differences were obvious at 6th and 12th months compared with the baseline ( P = 0.014   a n d   P = 0.042 , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment ( P = 0.023 ). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group ( P = 0.006 ). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy.
    Type of Medium: Online Resource
    ISSN: 1365-2710 , 0269-4727
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2006678-8
    SSG: 15,3
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  • 6
    In: PPAR Research, Hindawi Limited, Vol. 2020 ( 2020-12-31), p. 1-13
    Abstract: Liver fibrosis is a pathological process involving diffuse extracellular matrix (ECM) deposition in the liver. It is typical of many chronic liver diseases, including cirrhosis, and effective drugs are needed. In this study, we explored the protective effect of bergenin on liver fibrosis induced by carbon tetrachloride and bile duct ligation. A variety of molecular biological methods (qRT-PCR, western blotting, and immunohistochemistry) were employed to confirm the increased degree of hepatocyte injury and ECM formation in the disease model, consistent with autophagy and activation of the TGF-β pathway. Bergenin activated PPAR-γ and inhibited TGF-β and autophagy and decreased liver fibrosis by inhibiting hepatocyte necrosis and ECM formation in a dose-dependent manner. The results suggest that bergenin may be a promising drug candidate for the treatment of liver fibrosis.
    Type of Medium: Online Resource
    ISSN: 1687-4765 , 1687-4757
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2237981-2
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  • 7
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2022 ( 2022-9-9), p. 1-13
    Abstract: Objective. Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods. Forty db/db mice with diabetes ( random   blood   glucose ≥ 250   mg / dL ) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results. Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion. Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2455981-7
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  • 8
    Online Resource
    Online Resource
    Hindawi Limited ; 2013
    In:  Computational and Mathematical Methods in Medicine Vol. 2013 ( 2013), p. 1-12
    In: Computational and Mathematical Methods in Medicine, Hindawi Limited, Vol. 2013 ( 2013), p. 1-12
    Abstract: Quantitative reconstruction of bioluminescent sources from boundary measurements is a challenging ill-posed inverse problem owing to the high degree of absorption and scattering of light through tissue. We present a hybrid multilevel reconstruction scheme by combining the ability of sparse regularization with the advantage of adaptive finite element method. In view of the characteristics of different discretization levels, two different inversion algorithms are employed on the initial coarse mesh and the succeeding ones to strike a balance between stability and efficiency. Numerical experiment results with a digital mouse model demonstrate that the proposed scheme can accurately localize and quantify source distribution while maintaining reconstruction stability and computational economy. The effectiveness of this hybrid reconstruction scheme is further confirmed with in vivo experiments.
    Type of Medium: Online Resource
    ISSN: 1748-670X , 1748-6718
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
    detail.hit.zdb_id: 2256917-0
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  • 9
    In: Computational and Mathematical Methods in Medicine, Hindawi Limited, Vol. 2021 ( 2021-12-27), p. 1-8
    Abstract: Objective. To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE). Methods. The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment. Results. After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups ( P 〈 0.05 ). The levels of neuron-specific enolase (NSE), S-100β protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter ( P 〈 0.05 ). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups ( P 〈 0.05 ). Conclusion. Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.
    Type of Medium: Online Resource
    ISSN: 1748-6718 , 1748-670X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2256917-0
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  • 10
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2019 ( 2019-03-03), p. 1-14
    Abstract: Objective . To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms. Methods . We used a β cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h. Result. The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of β cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group. Conclusion. FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with β cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected β -cells from oxidative stress induced by high glucose in vivo and in vitro . The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2148302-4
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