Uncontrolled inflammatory response and subsequent cardiomyocytes loss (apoptosis and pyroptosis) are closely involved in sepsis-induced myocardial dysfunction. Our previous study has found that ...geniposide (GE) can protect the murine hearts against obesity-induced inflammation. However, the effect of GE on sepsis-related cardiac dysfunction is still unknown. Mice were exposed to lipopolysaccharide (LPS) to generate sepsis-induced myocardial dysfunction. And 50 mg/kg GE was used to treat mice for consecutive 7 days. Our results showed that GE treatment significantly improved survival rate and cardiac function, and suppressed myocardial inflammatory response, as well as myocardial loss in LPS-treated mice. Those effects of GE were largely abolished in NOD-like receptor protein 3 (NLRP3)-deficient mice. Further detection revealed that the inhibition of NLRP3 inflammasome activation depended on the reduction of p47phox by GE. GE treatment restored the phosphorylation and activity of AMP-activated protein kinase α (AMPKα) in the hearts of sepsis mice, and knockout of AMPKα abolished the protection of GE against reactive oxygen species (ROS) accumulation, NLRP3 inflammasome activation and cardiomyocytes loss in sepsis mice. In conclusion, our findings revealed that GE activated AMPKα to suppress myocardial ROS accumulation, thus blocking NLRP3 inflammasome-mediated cardiomyocyte apoptosis and pyroptosis and improving cardiac function in mice with sepsis.
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•Geniposide improved survival rate and cardiac function in septic mice.•Geniposide inhibited NLRP3 inflammasome in LPS-treated hearts.•Geniposide attenuated cell apoptosis and pyroptosis in vivo and in vitro.•Geniposide exerted its protection via activating AMPKα.
Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 ...on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An offline two-dimensional system combining a rat cardiac mascle cell membrane chromatography time-of-flight mass spectrometry （CMC-TOF/MS） with a high performance liquid chromatography ...time-of-flight mass spectrometry （HPLC-TOF/MS） was established for investigating the parent components and metabolites in rat urine samples after administration of the roots of Aconitum carmichaeli. On the basis of the analysis of the first dimension, retention components of the urine sample were collected into 30 fractions （one fraction per minute）. Then offline analysis of the second dimension was carried out. 34 compounds including 24 parent alkaloids and 10 potential metabolites were identified from the dosed rat urine, and then binding affinities of different compounds on cell membranes were compared and influences of some functional groups on activity were estimated with the semi-quantification and curve fitting method. As a result, binding affinities decreased along with the process of deacylation, debenzoylation and demethylation, which may be related to the alleviation of toxicity in the procedure of herb processing or metabolism. Moreover, some minor components in rat urine （Songorine, 14-benzoylneoline, Deoxyaconitine, etc. ） exerted relatively strong affinity on cell membranes are worth exploring. The results delivered by the system suggest that the CMC can be applied to in vivo study.
To compare the effects between computer-assisted and traditional cannulated screw internal fixation on treating femoral neck fracture.
The search was conducted in Embase, Pubmed, Web of Science, ...Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database from the beginning to August 2020. RevMan5.4 software, which was provided by the International Cochrane Group, was used for the meta-analysis comparing the differences in operation time, intraoperative bleeding volume, fluoroscopy frequency, fracture healing time, total drilling times, Harris score, fracture healing rate, and femoral head necrosis rate between computer-assisted and traditional methods groups.
A total of 1028 patients were included in 16 studies. Primary outcome indicators: Compared with the traditional method group, the computer-assisted group had less operative time (2RCTs, P < 0.00001; 8 non-RCTs, P = 0.009; Overall, P < 0.00001), intraoperative bleeding (1 RCTs, P < 0.00001; 9non-RCTs, P < 0.00001; Overall, P < 0.00001), femoral head necrosis rate (1 RCT, P = 0.11;7 non-RCTs, P = 0.09; Overall, P = 0.02) and higher Harris scores (1 RCT, P < 0.0001; 9 non-RCTs, P = 0.0002; Overall, P < 0.0001), and there were no significant differences in fracture healing rate between the two groups (5 non-RCTs, P = 0.17). Secondary outcomes indicators: The computer-assisted group had a lower frequency of intraoperative fluoroscopy and total number of drills compared with the traditional method group, while there was no significant difference in fracture healing time.
Compared with the traditional hollow screw internal fixation on the treatment of femoral neck fracture, computer-assisted percutaneous cannulated screw fixation can shorten the operation time and improve the operation efficiency and reduce the X-ray injury of medical staff and help patients obtain a better prognosis. Therefore, computer-assisted percutaneous cannulated screw fixation is a better choice for the treatment of femoral neck fracture. Study registration PROSPERO registration number CRD42020214493.
The Youganwo Formation oil shale located in the Maoming Basin represents a large commercially valuable lacustrine oil shale resource and a potential bio-shale gas reservoir in South China. With the ...aim of deepening the understanding of factors that influence organic matter enrichment, this research conducted a geochemical investigation to reconstruct the depositional paleoenvironment of bioproductivity, preservation and dilution. Youganwo Formation oil shale is mainly deposited in semi-deep to deep-lake environments with relatively warm and humid paleoclimate in the subtropical-temperate zone. The total organic carbon (TOC) content (1.46–11.85%), S2 values (4.79–115.80 mg HC/mg rock) and HI (328–1040 mg HC/mg TOC) indicate that the oil shale has a good oil source rock potential. TOC content, (S1 + S2) values and vitrinite reflectance values show that its marginally mature organic matter (OM) belongs to kerogen type I-III with good oil-generating potential.
A 3rd order sequence was identified in the Yougnwo formation. Subsequently, the multiple factors including bioproductivity, preservation and dilution that control the OM enrichment of oil shale within system tracts were discussed. Moderate-quality oil shales (Oy-1) were developed in the transgressive systems tract (TST) in an oxidizing condition with abundant detrital input. High-quality oil shales (Oy-2) were deposited during the high-stand systems tract (HST) with increased accommodation space, improved preservation conditions, warm and humid climate, higher water bioproductivity and minimum detrital matter input. During the regressive systems tract (RST, Oy-3), higher detrital matter input and fresher water led to lower TOC values. Among these multiple factors, dilution condition was the major one that influences OM abundance and variation on the basis of sufficient organic matter input. Thus, OM enrichment models of Oy-1, Oy-2 and Oy-3 sub-members were established. The OM enrichment and quality in oil shale were controlled by the combined effect of bioproductivity, preservation, and dilution.
The inducible IκB kinase (IKKi/IKKε) is a recently described serine-threonine IKK-related kinase. Previous studies have reported the role of IKKi in infectious diseases and cancer. However, its role ...in the cardiac response to pressure overload remains elusive. In this study, we investigated the effects of IKKi deficiency on the development of pathological cardiac hypertrophy using in vitro and in vivo models. First, we developed mouse models of pressure overload cardiac hypertrophy induced by pressure overload using aortic banding (AB). Four weeks after AB, cardiac function was then assessed through echocardiographic and hemodynamic measurements. Western blotting, real-time PCR and histological analyses were used to assess the pathological and molecular mechanisms. We observed that IKKi-deficient mice showed significantly enhanced cardiac hypertrophy, cardiac dysfunction, apoptosis and fibrosis compared with WT mice. Furthermore, we recently revealed that the IKKi-deficient mice spontaneously develop cardiac hypertrophy. Moreover, in vivo experiments showed that IKKi deficiency-induced cardiac hypertrophy was associated with the activation of the AKT and NF-κB signaling pathway in response to AB. In cultured cells, IKKi overexpression suppressed the activation of this pathway. In conclusion, we demonstrate that IKKi deficiency exacerbates cardiac hypertrophy by regulating the AKT and NF-κB signaling pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and ...Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, β cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, β cell function (homeostasis model assessment β-cell function index (HOMA-β) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum β-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.
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