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Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.
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Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.
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Objective To investigate the value of echocardiography in assessing the right heart function of patients with chronic obstructive pulmonary disease (COPD). Methods Forty-four COPD patients who were treated in Beijing Anzhen Hospital of Capital Medical University, from April 2016 to April 2017, were selected as COPD group; and 12 healthy physical examiners were included in healthy control group during the same period. Patients were divided into COPD with pulmonary hypertension (PH) group and COPD without PH group. All subjects were routinely examined by transthoracic echocardiography. The parameters of right heart function of all subjects were measured by echocardiography according to 2010 guideline of American Society of Echocardiography (ASE). Independent sample t test was used to compare echocardiographic routine parameters and recommended parameters of ASE guideline between COPD group and healthy control group. One-way analysis of variance was used to compare the routine parameters of echocardiography and the recommended parameters of the ASE guide in the patients of COPD with PH group and COPD without PH group and the healthy control group. SNK-q test was used for comparison between groups. Results The right ventricle diameter (RVD) in group COPD was wider than that in healthy control group [(20.68±4.21) mm vs (18.17±1.75) mm], and the difference was statistically significant (t=2.92, P=0.005). There was no significant difference in the right ventricular outflow tract (RVOT), main pulmonary artery diameter (MPAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) between the COPD group and the healthy control group. Compared with the healthy control group, the diameter of right ventricle basal segment in the COPD group increased [(35.92±8.12) mm vs (27.75±3.17) mm], tricuspid annular plane systolic excursion (TAPSE) decreased [(19.61±4.08) mm vs (22.67±2.67) mm], right ventricular index of myocardial performance (RIMP) increased [(0.52±0.10) cm/s vs (0.43±0.04) cm/s)], and the differences were statistically significant (t=3.39, P=0.001; t=-2.44, P=0.019; t=4.31, P ＜ 0.001). There was no significant difference in right atrium area, E/A, E/E' and S' between COPD group and healthy control group. There was no significant difference in RVOT, RVD, MPAD, LVEDD, LVESD and LVEF in the patients of COPD with PH group and COPD without PH group and in the healthy control group. There was no significant difference in the right atrium area, E/A, E/E', TAPSE and S'. The right ventricular basal segment diameter and RIMP of COPD with PH group and COPD without PH group were higher than those of healthy control group [(37.99±9.66) mm, (34.47±6.70) mm vs (27.75±3.17) mm; (0.54±0.13) cm/s, (0.51±0.08) cm/s vs (0.43±0.04) cm/s]. The differences were statistically significant (q=6.960, 4.905, 5.796, 4.348, all P＜0.05). However, there was no significant difference in right ventricular basal segment diameter and RIMP between COPD with PH group and COPD without PH group. The RVWT of COPD with PH group was higher than that of COPD without PH group [(5.29±0.69) mm vs (4.54±0.70) mm], and the difference was statistically significant (t=3.313, P=0.002). Conclusions The method recommended in the ASE guidelines for this study was more sensitive than conventional methods for the detection of changes in the structure of the right heart. The change of the right ventricular structure was the first manifestation of right heart involvement in COPD patients, and then the systolic function of the right ventricle diminished. The long-term effect of pulmonary hypertension was thickening of the right ventricular wall at the early stage and then enlargement of the right ventricle.
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Objective To explore the value of layer-specific strain in assessment of left ventricular function in patients with heterozygous familial hypercholesterolemia (HeFH) with normal left ventricular ejection fraction (LVEF).Methods Thirty-four patients with diagnosed HeFH and underwent transthoracic echocardiography were included as HeFH group,while 29 healthy volunteers were taken as control group.EchoPAC software was used to obtain endocardial longitudinal strain (LSendo),myocardial longitudinal strain (LSmyo) and epicardial longitudinal strain (LSepi) of the epicardial,and then statistical analysis was performed.Results LSendo and LSmyo in HeFH group were significantly lower than those in control group (P＜0.001).LSendo and LSmyo were negatively correlated with total cholesterol and low density lipoprotein cholesterol (all P＜0.05).Conclusion Layer-specific strain of left ventricular is of great value in assessing early myocardial damage in patients with HeFH.
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Objective Observe the clinical effect of the controllable airbag elastic chest strap after the breast cancer operation,studying the clinical value of the controllable airbag elastic chest strap.Methods Between May.2009 and Oct.2012,71 women having surgery for breast cancer at The Affiliated Second Hospital of Nan Hua University Oncology Center.They were to receive either a common thoracic girdle compressed binding(n =35),or the controllable airbag elastic chest strap compressed binding (n =36) at the postoperation.The following complications were evaluated:the incidence of seroma formation and duration,the incidence of skin flap swelling,and the dressing time.Results Thirty-five patients with common thoracic girdle is 14 cases of subcutaneous effusion,fluid rate was 40.0％,the effusion duration 7 to 31 days,an average of 17.6 ±7.3 days,15 cases with skin redness (disc),swelling rate is 42.9％,the average treatment time 18.7 ±3.5 minutes; With the controllable airbag elastic chest strap group of six cases of subcutaneous effusion,fluid rate was 16.7％,the duration of effusion 5-14days,an average of 10.5 ± 3.9 days,skin redness (disc),swelling rate is 13.9％,the average treatment time 12.2 ± 2.4 minutes.Conclusions The controllable airbag elastic chest strap can reduce subcutaneous effusion,reduce skin flapswelling,saving the treatment time,is worth promoting in the clinical medical supplies.
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Objective To investigate histopathological change of axillary lymph nodes and ecto-node encroachment of breast cancer following neoadjuvant chemotherapy in locally advanced breast cancer.Methods Second Hospital Affiliated to University of South China had received 86 patients with breast carcinoma from June 2002 to August 2009,these patients suffered lump over 5 cm and homonymy nonfusion lymphadenectasis.All samples were grouped on the basis of wether or not accept neoadjuvant chemotherapy.The first group included 46 patients,who were reluctant to receive neoadjuvant chemotherapy,operated after pricking pathological diagnosis.There were 40 patients with metastatic axillary lymph nodes and 17 patients with axillary ecto-node encroachment in the first group.The second group included 40 patients,who were voluntary to receive neoadjuvant chemotherapy,and operated after pricking pathological diagnosis and received three cycles of neoadjuvant chemotherapy on average.There were 26 patients with metastatic axillary lymph nodes and 6 patients with axillary ecto-node encroachment in the second group.Results The rate of metastatic axillary lymph nodes was 86.9% and the rate of axillary ecto-node encroachment was 36.9% in the first group,while 65% and 15% respectively in the scond group.There were significant deference in the rate of metastatic lymph node and axillary ecto-node encroachmen between two groups.Conclusion Neoadjuvant chemotherapy is effective to treat metastatic lymph node and axillary ecto-node encroachment in breast cancer.
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A single factor duplicate test was designed to investigate whether bovine recombinded resistin impacts the expression of pyruvate carboxylase (PC) mRNA and the activity of PC in vitro culture bovine hepatocyte.Bovine recombinded resistin was added to the media with 0,25,50,100,200 and 400 ng/L.Abundance of PC mRNA in bovine hepatocyte,which was cultured with bovine recombinded resistin for 12 hours,was determined by real-time fluorescence quantitative RT-PCR,and activity of PC was determined by colourimetry.The results showed that bovine recombinded resistin could downregulate the expression of PC mRNA and the activity of PC in vitro culture bovine hepatocyte.
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Objective To study the expressions of SKP2 and p27 in gastric carcinoma and pericancerous tissues and to detect the relationship between their expressions and clinicopathological features. Methods Forty-nine cases of gastric carcinoma spicemen and 20 cases of tissue adjacent to the carcinoma were cut and made into paraffin-embedded slices. The expressions of SKP2 and p27 were then detected by SP immunohistochemical method. Results The positive expression rate and score of SKP2 were both significantly higher in the gastric carcinoma tissues than those in pericancerous tissues (P
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By comparing with the molecule weights, retention times and product ion spectra of the standards, the cholic acid, deoxycholic acid and chenodeoxycholic acid were identified in the traditional Chinese compound medicine——“Qingkailing” injection by high performance liquid chromatography/mass spectrometry/mass spectrometry. Two other isomers of cholic acid and deoxycholic acid were also found, but tieir detail structure was still unknown due to the absence of standards. A quantitative method to determine cholic acid in the medicine was established and studied. An internal standard was used in quantitative analysis. When the concentration of cholic acid is from 875 ng/L to 140 μg/L, the chromatographic peak area and concentration are of good linear relation. The linear correlation coefficient was determined to be 0.9999 and the RSD is 2.04%. This method is simple, selective and highly sensitive, which is helpful for the quality control of traditional Chinese medicine.