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Inflammatory bowel disease (IBD), as an idiopathic inflammatory disease of the intestinal tract, consisting mainly of Crohns disease and ulcerative colitis, which can involve the rectum, colon and ileum, and whose pathogenesis is still not fully understood. The initiation of intestinal inflammation associated with IBD and its chronieity begins with increased intestinal permeability caused by intestinal epithelial barrier disruption. The anti-permeability of the intestinal epithelial barrier is maintained by tight junction in the apical region of the intestinal epithelial cells, and disruption of the tight junction structure is closely associated with intestinal epithelial barrier damage and the development of IBD. Therefore, it is significant to find drugs for the prevention and treatment of IBD using tight junctions as regulatory targets. In recent years, many small molecules of natural product origin have been reported to improve the effects of IBD. In particular, we review the compounds that have the function of repairing intestinal epithelial barrier and protecting tight junction structure, in order to provide research ideas for the design and development of new drugs for the prevention and treatment of IBD.
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Objective: To evaluate the effect of Wendler Glottoplasty to elevate vocal pitch in transgender women. Methods: The voice parameters of pre-and 3-month post-surgery of 29 transgender women who underwent Wendler Glottoplasty in department of otorhinolaryngology head and neck surgery of Beijing Friendship Hospital from January, 2017 to October, 2020 were retrospectively analyzed. The 29 transgender women ranged in age from 19-47 (27.0±6.3) years old. Subjective evaluation was performed using Transsexual Voice Questionnaire for Male to Female (TVQMtF). Objective parameters included fundamental frequency (F0), highest pitch, lowest pitch, habitual volume, Jitter, Shimmer, maximal phonation time (MPT), noise to harmonic ratio (NHR) and formants frequencies(F1, F2, F3, F4). SPSS 25.0 software was used for statistically analysis. Results: Three months after surgery, the score of TVQMtF was significantly decreased [(89.9±14.7) vs. (50.4±13.6), t=11.49, P<0.001]. The F0 was significantly elevated [(152.7±23.3) Hz vs. (207.7±45.9) Hz, t=-6.03, P<0.001]. Frequencies of F1, F2 and F3 were significantly elevated. No statistical difference was observed in the frequencies of F4. The highest pitch was not significantly altered while the lowest pitch was significantly elevated [(96.8±17.7) Hz vs. (120.0±28.9) Hz, t=-3.71, P=0.001]. Habitual speech volume was significantly increased [(60.0±5.2) dB vs. (63.6±9.6) dB, t=-2.12, P=0.043]. Jitter, Shimmer, NHR and MPT were not obviously altered (P>0.05). Conclusions: Wendler Glottoplasty could notably elevate the vocal pitch, formants frequencies and degree of vocal femininity in transgender women without affecting phonation ability and voice quality. It can be an effective treatment modality for voice feminization.
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Humans , Male , Female , Young Adult , Adult , Middle Aged , Transgender Persons , Retrospective Studies , Speech Acoustics , Voice Quality , PhonationABSTRACT
Under the leadership of the Beijing Winter Olympic Organizing Committee and the Beijing Municipal Health Commission, the Beijing Emergency Center, as the designated medical institution for the 2022 Beijing Winter Olympic Games, has completed the first aid support task of this Winter Olympic Games with other medical institutions. The author systematically analyzed the development of each link in the pre-hospital emergency support for the 2022 Beijing Winter Olympic Games, summarizes the key links of the entire Winter Olympics cycle, such as the construction of the organizational system, the formulation of support plans, and the training of support personnel, and analyzed the results of related work, so as to provide reference for the pre-hospital emergency support for China to host large-scale international events in the future.
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Abnormality of glycogen synthase kinase-3 (3 ( GSK- 3(i) triggers a deleterious consequence of disorder of bone me¬tabolism , contributing to osteoporosis.Osteoporosis is character¬ized by bone loss and destruction of bone microstmcture, which often leads to the increase of incidence rate of fracture.Natural products derived from plants can be used as potential dmgs to prevent and treat osteoporosis.In this review, we elaborates on the intimate connection between GSK-3p and bone metabolism.and summarizes natural products of flavonoids, isoflavoncs, pol¬ysaccharides and saponins, phenols, alkaloids and amine deriv¬atives regulating GSK-3(3 pathway in the prevention and treat¬ment of osteoporosis, which may provide scientific evidence for further development of drugs that may effectively prevent and treat osteoporosis.
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Objective:To study the differences in genetic relationship， shape， size， and flavonoid content between traditional and nontraditional medicinal varieties of Citri Reticulatae Semen produced in Sichuan province as well as their equivalence. Method:Six batches of traditional medicinal Citri Reticulatae Semen （<italic>Citrus reticulata</italic> 'Dahongpao'） and 23 batches of nontraditional medicinal varieties were collected， and their genetic relationship was explored using sequence-related amplified polymorphism （SRAP） markers. Following the observation of their shapes and sizes under a stereomicroscope， the contents of naringin， hesperidin， and neohesperidin were measured by high performance liquid chromatography （HPLC）. SIMCA 14.1 software was used for cluster analysis of their shapes， sizes， and flavonoid contents， thus figuring out the similarities between the traditional and nontraditional medicinal varieties in character， size， and chemical components. Result:SRAP markers-based genetic relationship analysis effectively distinguished different Citri Reticulatae Semen varieties from each other. Some samples collected from the same or adjacent places exhibited a close genetic relationship and they shared high similarities in shape， size， and flavonoid content. However， the traditional medicinal Citri Reticulatae Semen was still quite different from most nontraditional medicinal varieties. Conclusion:The analysis of differences in genetic materials， appearance， character， and active ingredient content between the traditional and nontraditional medicinal varieties revealed that the equivalence<italic> </italic>of <italic>C.</italic> <italic>reticulata</italic> 'Ponkan' samples from some regions with the traditional medicinal variety was the largest， enabling them to be considered as the emerging medicinal variety.
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Background and Purpose- 1/2ABC has been used widely for assessing the volume of intracerebral hematoma. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we re-explored the formula of hematoma volume to find a method that can calculate hematoma volumes accurately, reliably, and quickly. Methods- Computed tomography imaging data of 257 patients with intracerebral hemorrhage were collected. Hematoma volumes were estimated using 3-dimensional Slicer and 7 formulas (π/6ABC, 1/2ABC, 1/3ABC, 2/3SH, 1/2SH, π/6SH, and 2.5/6ABC). Taking the hematoma volumes measured by 3-dimensional Slicer as the reference standard, the accuracy and reliability of the 7 formulas were evaluated. Furthermore, the time needed to calculate hematoma volumes by the 1/2SH method was noted for further analysis. Results- (1) The accuracy of the 7 formulas based on the error analysis from the highest to the lowest was: π/6SH, 1/2SH, 2.5/6ABC, 1/3ABC, 1/2ABC, and π/6ABC or 2/3SH. According to concordance analysis and receiver operating characteristic curve analysis, the results from the highest to lowest were as follows: 1/2SH, π/6SH, 2.5/6ABC, 1/3ABC, 1/2ABC, 2/3SH, and π/6ABC. After categorizing cases according to size, shape, and location of hematoma, the results were almost the same as the results for overall accuracy evaluation in any subgroup. (2) Intraclass correlation coefficient (ICC) of 1/2SH in intra and inter-researcher were 0.998 and 0.989, respectively. For the formula π/6SH, intraclass correlation coefficient was the same as that of 1/2ABC. Kappa values of 1/2SH for intra- and inter-observer were 0.992 and 0.913, respectively. For π/6SH, kappa values of within- and between-reader were 0.984 and 0.904, respectively. (3) The average time taken to calculate hematoma volumes by 1/2SH was 74 seconds. Conclusions- The 1/2SH and π/6SH are accurate, reliable, and rapid methods for calculating hematoma volumes. The accuracy and reliability of 1/2SH were slightly higher than those of π/6SH.
Subject(s)
Cerebral Hemorrhage/diagnostic imaging , Hematoma/diagnostic imaging , Tomography, X-Ray Computed , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Pre-hospital rescue is key to the emergency medical system. Based on the current pre-hospital emergency standardized system construction in China, the authors explored the standardization of pre-hospital emergency system construction, command dispatch and emergency service quality control standardization, pre-hospital classification standardization, pre-hospital emergency service capacity standardization, pre-hospital emergency and intra-hospital emergency connection standardization, standardized training for pre-hospital emergency doctors and nurses. These efforts aim to achieve such rescue and transfer criteria for patients, as " vicinity, urgency, professional needs, and intension of both patients and their families" . Such criteria if met can further reduce emergency response time and shorten the emergency radius, hence improving emergency medical services.
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As a key part of the emergency medical system,pre-hospital emergency service proves critical for critical care,higher pre-hospital care success rate,improvement of patient outcome,and promotion of health recovery.This paper analyzed the status quo of pre-hospital emergency services information,discussed the application of information technology in pre-hospital industries including command and dispatch system,ambulance real-time positioning and tracking system,pre-hospital emergency video surveillance system,medical record system,electronic patient health file system,electronic payment system,and data mining and analysis system.Furthermore,it also discussed the prospect of sizably upgrading prehospital emergency service and building intelligent pre-hospital emergency coordination system.
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As a key part of the emergency medical system, pre-hospital emergency service proves critical for critical care, higher pre-hospital care success rate, improvement of patient outcome, and promotion of health recovery. This paper analyzed the status quo of pre-hospital emergency services information, discussed the application of information technology in pre-hospital industries including command and dispatch system, ambulance real-time positioning and tracking system, pre-hospital emergency video surveillance system, medical record system, electronic patient health file system, electronic payment system, and data mining and analysis system.Furthermore, it also discussed the prospect of sizably upgrading pre-hospital emergency service and building intelligent pre-hospital emergency coordination system.
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BACKGROUND: Our previous study demonstrated that bone marrow mesenchymal stem cells (MSCs) presented with a low survival rate and newly formed vascular-like structures was sparsely distributed in the local infarct tissues after cell transplantation, which certainly impaired the therapeutic efficacy. Long non-coding RNA-H19 (lncRNA-H19) has been confirmed to be associated with MSCs differentiation and mediate vascularization. OBJECTIVE:To observe the influence of lncRNA-H19 on the survival and vascularization potential of MSCs in vitro and to explore the possible mechanism. METHODS:MSCs were obtained and cultured in vitro.Cells were divided into five groups:MSCs+H19,MSCs+H19 negative control (MSCs+H19 NC), MSCs+si-H19, MSCs+si-H19 negative control (MSCs+si-H19 NC) and MSCs groups. MSCs+H19 and MSCs+H19 NC groups were transfected with lncRNA-H19 and lncRNA-H19 scramble RNA respectively, while MSCs+siH19 and MSCs+si-H19 NC groups were transfected with lncRNA-H19 siRNA and lncRNA-H19 siRNA scramble respectively. Cells were cultured under hypoxic-ischemic condition (serum-free medium, 1% O2) for 24 hours. Then, cell proliferation and apoptosis were evaluated using MTS and TUNEL, respectively. Cell supernatant from each experimental group was further co-cultured with human umbilical vein endothelial cells to induce vascularization. The expression of vascular endothelial growth factor A (VEGFA) was thereafter detected using western blot assay. RESULTS AND CONCLUSION: Compared with MSCs+H19 NC and MSCs groups, MSCs+H19 group presented with significantly higher proliferation rate, lower apoptosis percentage and a larger number of vascular branches on matrigel (P < 0.01). There was a significantly higher expression of VEGFA in the MSCs+H19 group than MSCs+H19 NC and MSCs groups. Compared with the MSCs and MSCs+si-H19 NC groups, MSCs+H19 group presented with significantly lower proliferation rate, higher apoptosis percentage and a less number of vascular branches on matrigel (P < 0.01). In addition, VEGFA expression was distinctly downregulated in the MSCs+si-H19 group in comparison with the MSCs+si-H19 NC and MSCs groups. These findings indicate that lncRNA-H19 effectively promotes MSCs survival and vascularization under hypoxic-ischemic condition in vitro,and this effect may be associated with the upregulation of VEGFA.
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Objective To assess the application of MRI in diagnosis of oblique vaginal septum syndrome (OVSS).Methods Clinical and imaging data of 41 patients with OVSS confirmed by surgery from March 2011 to November 2016 were retrospectively analyzed.Results The average age of patients was 20.5 year (10-46 years).The primary clinical symptoms were menorrhalgia (16 cases) and menorrhagia (13 cases).There were 12 cases of type Ⅰ,23 cases of type Ⅱ,5 cases of type Ⅲ and 1 case of type Ⅳamong 41 cases of OVSS.The resections for OVSS were performed in 35 cases.Forty two cases were diagnosed as OVSS by MRI scan,and 41 were confirmed by surgery,the accuracy of MRI diagnosis was 97.6％ (41/42).MRI showed uterus didelphys,hydrocolpos or hematocolpos with varying degrees,and revealed ipsilateral renal agenesis in all 41 cases.Conclusion MRI scan can accurately diagnose oblique vaginal septum syndrome and provide comprehensive information for clinical treatment.
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BACKGROUND:Our previous work demonstrated that bone marrow mesenchymal stem cells (BMSCs) transplantation could improve cardiac function in rats with myocardial infarction.However,the overall efficacy was unsatisfactory,and there was a low efficiency of BMSCs differentiating into cardiomyocytes in the local infarct myocardium.OBJECTIVE:To transfect long non-coding RNA-Braveheart (IncRNA-Bvht) into BMSCs in order to observe whether it could promote cardiomyocyte differentiation of BMSCs in vitro.METHODS:pLVX-IRES-ZsGreen1-IncRNA-Bvht vector was constructed and applied to transfect IncRNA-Bvht into bMSCs,and then,the transfection efficiency was detected.BMSCs were obtained from C57BL/6 mice and cultured ir vitro.Passage 3 cells were divided into three groups:BMSCs group,null vector group and IncRNA-Bvht group.All cells in the three groups were cultured in the normal condition for 48 hours and cardiomyocytes differentiation was induced by 5-azacytidine for another 24 hours followed by 2-week culture under normal conditions.Cardiomyocyte differentiation of BMSCs was observed under fluorescence microscopy and expression of cardiac specific cell markers including troponin T and myosin were examined using immunofluorescent staining,western blot assay,and qRT-PCR.RESULTS AND CONCLUSION:Cell morphological changes could be observed in all the groups 2 weeks after the induction.Interconnected cells arranged consistently in all the three groups.Immunofiuorescent staining results showed that the expression of troponin T and myosin was notably positive,and the proportion of troponin T positive cells was significantly increased.qRT-PCR and western blot assay results indicated that there were significantly increased levels of troponin T and myosin in the IncRNA-Bvht group as compared with the BMSCs and null vector groups (P ＜ 0.01),suggesting that IncRNA-Bvht could efficiently promote cardiomyocyte differentiation of BMSCs in vitro.
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BACKGROUND: Our previous studies demonstrated that cardiac stem cells (CSCs) transplantation could improve cardiac function in rats with myocardial infarction (MI). However, the overall survival and cardiac differentiation of CSCs were low. OBJECTIVE: To investigate the effect of hypoxia preconditioning on CSCs proliferation and cardiogenic differentiation and the role of hypoxia induced factor-1alpha (HIF-1α)/apelin/putative receptor protein related to the angiotensin receptor AT1 (APJ) pathway in the procedure. METHODS: Cells cultured in vitro experienced exposure to hypoxia (1% O2) for 24 hours. Cardiogenic differentiation was induced by using 5-azacytidine for another 24 hours. Then, cells were cultured in normal condition for 2 weeks. Normoxia (20% O2) was used as a negative control during the whole process. Cell proliferation was detected using MTS method and expressions of HIF-1α, apelin, cTnT and APJ were detected using western blot assay after 24 hours of preconditioning and 2 weeks after the induction of differentiation; the percentage of cTnT-positive cardiomyocyte-like cells was observed by immunofluorescence staining. RESULTS AND CONCLUSION: Compared with the normoxia group, the hypoxia group presented a higher proliferation rate and a higher absorbance value at 490 nm (P < 0.01); the protein expressions of HIF-1α, apelin and APJ were all enhanced after hypoxia exposure for 24 hours and 2 weeks after the induction of differentiation (P < 0.01); the percentage of cTnT-positive cells was greatly increased in the hypoxia group (P < 0.01), and the expression of cTnT was also significantly intensified (P < 0.01). To conclude, hypoxia preconditioning could promote the proliferation and cardiogenic differentiation of CSCs, and the activation of HIF-1α/Apelin/APJ pathway might be involved in this process.
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<p><b>OBJECTIVE</b>To investigate the value of serum globulin levels before treatment in predicting the prognosis of patients with nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>A total of 127 patients with non-disseminated NPC were recruited between January, 2009 and December, 2013 at Nanfang Hospital. The pretreatment serum globulin levels were analyzed with the receiver-operating characteristic (ROC) curve analysis to select the cut-off point for low and high pretreatment serum globulin levels. Kaplan-Meier and multivariable analyses were used to evaluate the predictive value of serum globulin levels.</p><p><b>RESULTS</b>The ROC curve analysis determined 30.05 g/L as the optimal cut-off value for pretreatment serum globulin level, which was significantly associated with gender (P=0.024) and N stage (P=0.016). Kaplan-Meier analysis showed that a high pretreatment serum globulin level (>30.05 g/L) significantly predicted poor progression-free survival (P=0.019), overall survival (P=0.034) and distant metastasis-free survival (P=0.049); multivariate analysis identified pretreatment serum globulin level as an independent prognostic factor for progression-free survival (HR=2.344, P=0.031).</p><p><b>CONCLUSION</b>Pretreatment serum globulin level may serve as a valuable marker to predict the prognosis of patients with NPC.</p>
Subject(s)
Humans , Carcinoma , Disease-Free Survival , Kaplan-Meier Estimate , Multivariate Analysis , Nasopharyngeal Neoplasms , Blood , Diagnosis , Prognosis , ROC Curve , Serum GlobulinsABSTRACT
No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11. 24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.
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Objective To investigate the effects of siRNA targeting decoy receptor 3 on the cell proliferation of ovarian carcinoma cell CAOV3. Methods We constructed siRNA targeting decoy receptor 3,which was transfected into ovarian carcinoma cells CAOV3 , and observed the effects of DcR3 siRNA on the cell proliferation of CAOV3 cell by MTT experiment. The experiment contained 3 groups, including the normal control group (CAOV3 cell was not transfected), the negative control group (CAOV3 cell was transfected with blank vector) and the experimental group (CAOV3 cell was transfected with DcR3 siRNA). The expression levels of DcR3 mRNA were detected by Real-time PCR. Results DcR3 siRNA recognized and degraded DcR3 mRNA in CAOV3 cells of the experimental group. DcR3 mRNA of the experimental group was significantly decreased. The proliferation of CAOV3 cell was significantly decreased by DcR3 siRNA comparing with the normal control group and negative control group (P < 0.01). Conclusion DcR3 siRNA can inhibit the proliferation of ovarian cancer cell line CAOV3 by recognized and degraded DcR3 mRNA.
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No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.
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Animals , Female , Male , Rats , Bambusa , Chemistry , Diet , Powders , Rats, Sprague-Dawley , Toxicity Tests, AcuteABSTRACT
In this study, 23 groups of suited typical soil-wheat grain samples were collected from different locations of Beijing city (central city, suburban plain and exurban plain), the accumulation, chemical forms and bioavailability of heavy metals in arable soils under different human activity intensity were analyzed, and their source identifications and health risk were discussed. The results showed that (1) Urban soils exhibited Pb contamination with an average concentration (35.59 mg x kg(-1)) above the WHO limit, probably due to the emission of traffic activities and industrial processes. In addition, long-term sewage irrigation and other agricultural activities led to local metal contamination in the suburban agricultural soils. (2) Cu, Zn and Pb were predominantly associated with the residual (35%-75%) and organic (23%-53%) fractions, followed by Fe/Mn oxide (1%-19%), and very small proportion of carbonate (n. d.-5%) and exchangeable (n. d.-2%) fraction. Furthermore, compared with the suburban agricultural soils, Pb, Zn and Cu in the urban agricultural soils showed higher mobility, whereas the exurban agricultural soils presented the lowest mobility. For Cd, the order was contrary. Besides, Cd showed the highest bioavailability among the four metals in suburban and exurban arable soils due to its considerable proportion of exchangeable (13% -31%) and carbonate fractions (11%-27%). (3) Cd and Zn contents in wheat grains were largely dependent on the Fe/Mn ox. fractions in the studied soils (P < 0.05, r were 0.43-0.7). (4) Pb and Zn concentrations in wheat grains in some of the urban and suburban agricultural soils were above the standard limit, which might bring potential risk for the health of the local residents.
Subject(s)
Crops, Agricultural , Environmental Monitoring , Metals, Heavy/analysis , Soil Pollutants/analysis , Chemical Fractionation , China , Cities , Crops, Agricultural/growth & development , Metals, Heavy/chemistry , Soil/chemistryABSTRACT
A prolonged or excessive adrenergic activation leads to myocyte loss and heart dysfunction; however, how it contributes to heart failure remains poorly defined. Here we show that isoproterenol (ISO) induced aberrant endoplasmic reticulum (ER) stress and apoptotic cell death, which was inhibited by activating the AMP-activated protein kinase (AMPK) in vitro and in vivo. Persistent ISO stimulation suppressed the AMPK phosphorylation and function, resulting in enhanced ER stress and the subsequent cell apoptosis in cardiomyocytes in vitro and in vivo. AMPK activation decreased the aberrant ER stress, apoptosis, and brain natriuretic peptide (BNP) release in ISO-treated cardiomyocytes, which was blocked by AMPK inhibitor Compound C. Importantly, increased ER stress and apoptosis were observed in ISO-treated cardiomyocytes isolated from AMPKα2(-/-) mice. Inhibition of ER stress attenuated the apoptosis but failed to reverse AMPK inhibition in ISO-treated cardiomyocytes. Moreover, metformin administration activated AMPK and reduced both ER stress and apoptosis in ISO-induced rat heart failure in vivo. We conclude that ISO, via AMPK inactivation, causes aberrant ER stress, cardiomyocyte injury, BNP release, apoptosis, and hence heart failure in vivo, all of which are inhibited by AMPK activation.
Subject(s)
AMP-Activated Protein Kinases/genetics , Heart Failure/chemically induced , Isoproterenol/adverse effects , Metformin/pharmacology , Myocytes, Cardiac/drug effects , AMP-Activated Protein Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/deficiency , Animals , Apoptosis/drug effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation , Heart Failure/enzymology , Heart Failure/pathology , Heart Failure/prevention & control , Male , Mice , Mice, Knockout , Myocardium/enzymology , Myocardium/pathology , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Natriuretic Peptide, Brain/metabolism , Phosphorylation , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Rats , Rats, Sprague-Dawley , Signal TransductionABSTRACT
BACKGROUND: The objective of the present study was to determine the effect of various concentrations of oleic acid (OA) on KATP channel expression and the potential relationship to exogenous nitrogen monoxide and protein kinase C levels. METHODS: Human umbilical artery smooth muscle cells (HUASMCs), between the 7th and 10th passages, were divided into control group, OA group (final OA concentration of 0, 50, 100 or 200 µmol/L), nitric oxide (NO) intervention group, protein kinase C inhibitor group or GF-109203X (GFX) intervention group. Western immunoblotting was used to detect the protein expression of the KATP channel subunit Kir6.1. Also, quantitative real-time polymerase chain reaction analysis to determine Kir6.1 messenger RNA levels and whole-cell patch clamping to measure KATP currents were performed. RESULTS: The results suggested that OA inhibited Kir6.1 protein and messenger RNA expression in HUASMCs. Under a high concentration of potassium (140 mmol/L), 100 µmol/L OA significantly reduced ATP-sensitive potassium current density, whereas a low extracellular concentration of potassium (5.4 mmol/L) did not influence KATP density. Pretreatment with either exogenous NO or GFX weakened the OA-induced inhibition of KATP in HUASMCs. CONCLUSIONS: The study demonstrated that OA inhibited Kir6.1, a KATP channel subunit, in HUASMCs, and indirectly inhibited the KATP current. In addition, the results indicated that NO and/or GFX partially reversed OA inhibition in HUASMCs.
