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Purpose@#Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear. @*Materials and Methods@#We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC. @*Results@#Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression. @*Conclusion@#Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.
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Objective:To examine the association between macrophage migration inhibitory factor(MIF), Interleukin 6(IL-6), periodontal disease, and atherosclerosis in middle-aged and elderly individuals.Methods:This cross-sectional study enrolled 700 diabetic patients who were attending the endocrinology department of Beijing Hospital from January 2020 to December 2022.Out of these patients, 491 underwent a full-mouth periodontal examination.Among them, 106 were middle-aged and elderly.The study included 83 patients with complete data, aged between 45 and 70 years(mean age: 58.2±8.7 years).Among the included patients, 48 were male(57.8%)and 35 were female(42.2%).A questionnaire was administered to gather information about the patients, and serum levels of MIF and IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).The relationship between serum MIF and IL-6 levels and periodontitis and atherosclerosis was evaluated through univariate and multifactorial analyses conducted on middle-aged and elderly individuals.Results:There were 66 cases(79.5%)in the periodontitis stage Ⅰ/Ⅱ group and 17 cases(20.5%)in the stage Ⅲ/Ⅳ group.The serum MIF levels in the two groups were(2, 312.5±795.0)ng/L and(2, 939.8±665.0)ng/L, respectively( P<0.01).Similarly, IL-6 levels were(3.5±3.0)ng/L and(6.7±6.1)ng/L in the two groups( P>0.05).The findings revealed that for each 1 ng/L increase in MIF serum levels, the risk of severe periodontitis and increased carotid intima-media thickness(cIMT)increased by 0.1%.Furthermore, for each 1 ng/L increase in serum MIF and IL-6 levels, the risk increased by 0.2% and 38.9% respectively.Serum MIF levels were found to be associated with atherosclerosis as well as with various factors related to periodontitis, including periodontal probing depth, bleeding index, clinical attachment level, periodontal probing depth≥4 mm sites, clinical attachment level≥5%, and bleeding index >2%(all P<0.05). Conclusions:This study investigates the correlation between MIF and IL-6 levels with Periodontal disease and Atherosclerosis in middle-aged and elderly individuals.
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BACKGROUND: To understand the long-term oncologic outcomes of open radical cystectomy (ORC) versus laparoscopic radical cystectomy (LRC) versus robot-assisted radical cystectomy (RARC) for bladder cancer (BCa). Therefore, we performed the conventional meta-analysis and network meta-analysis to evaluate the long-term oncologic outcomes of ORC, LRC, and RARC for BCa. METHODS: A systematic search of PubMed, Embase, Cochrane Library, Medline, and Web of science was performed up until July 1, 2021. Long-term oncologic outcomes include the 5-year overall survival (OS) rate, the 5-year recurrence-free survival (RFS) rate, and the 5-year cancer specific-survival (CSS) rate. The Bayesian network analysis has been registered in PROSPERO (CRD42020208396). RESULTS: We found that 10 articles (including 3228 patients) were included in our Bayesian network analysis. No significant differences were found between ORC, LRC, and RARC in long-term oncologic outcomes in either direct meta-analysis or network meta-analysis. Therefore, the clinical effects of 5-year OS, RFS, and CSS of RARC, LRC, and ORC are similar. But LRC may be ranked first in 5-year OS, RFS, and CSS compared to other surgical approaches by probabilistic analysis ranking via Bayesian network analysis. CONCLUSION: We found that there were no statistical differences in the 3 surgical approaches of RAPC, LPC, and OPC for Bca in long-term oncologic outcomes by direct meta-analysis. However, Subtle differences between these surgical approaches can be concluded that LRC may be a better surgical approach than RARC or ORC in long-term oncologic outcomes by probabilistic analysis ranking via Bayesian network analysis. Moreover, we need a large sample size and more high-quality studies to improve and verify further.
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Laparoscopy , Robotic Surgical Procedures , Robotics , Urinary Bladder Neoplasms , Bayes Theorem , Cystectomy , Humans , Postoperative Complications/surgery , Treatment Outcome , Urinary Bladder Neoplasms/surgeryABSTRACT
To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and β diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.
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Adult , Animals , Female , Humans , Male , Bacteria/genetics , Feces/microbiology , Gastrointestinal Microbiome/genetics , High-Throughput Nucleotide Sequencing , Intestines , Murinae/geneticsABSTRACT
Objective:To analyze and study the difficulties and countermeasures in the implementation of the Qualified Person(QP) system for stem cell clinical research, and share the experience of QP management practice in our hospital in order to promote and improve the construction of the QP management system in medical institutions.Methods:Comprehensive investigations were conducted to summarize and analyze the shortage of talents, unclear qualifications, unclear responsibilities, and lack of assessment standards in the QP system of medical institutions.Results:In view of the difficulties in the implementation of the current QP system, it is suggested to consider a combination of improving the system of laws and regulations, strengthening the top-level design of stem cell research institutions, clarifying the qualification threshold, refining QP responsibilities, continuing training and assessment system, establishing QP support system, etc.Conclusions:Medical institutions are responsible for stem cell clinical research, and the improvement of the QP system can promote the development of the cell industry in China.
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Objective: To find a suitable ecological cultivation measure to solve the problem of root-knot nematode disease of Panax quinquefolium (Panacis Quinquefolii Radix) and the heavy metals accumulating in its roots. Methods: Three-year-old P. quinquefolium was treated with four different combinations of microbial inoculant (MI) and garbage fermentation liquid (GFL) [the joint application of ‘TuXiu’ MI and Fifty potassium MI (TF), the combination use of ‘No. 1′ MI and Fifty potassium MI (NF), ‘Gulefeng’ poly-γ-glutamic acid MI (PGA), GFL], and the untreated control (CK). Here, high-throughput sequencing, ICP-MS and UPLC were employed to systematically characterize changes of microbial diversity and structure composition, heavy metals (As, Cd and Pb) content and ginsenoside content among different treatments. Results: The results revealed that different MIs and GFL could increase the root dry weight of P. quinquefolium, PGA enhanced it by 83.24%, followed by GFL (49.93%), meanwhile, PGA and GFL were able to lessen root-knot nematode disease incidence by 57.25% and 64.35%. The treatment of PGA and GFL can also effectively reduce heavy metals in roots. The As content in GFL and PGA was decreased by 52.17% and 43.48% respectively, while the Cd and Pb contents of GFL and PGA was decreased somewhat. Additionally, the content of total ginsenosides was increased by 42.14% and 42.07%, in response to TF and NF, respectively. Our metagenomic analysis showed that the relative abundance of particular soil microbial community members related to the biocontrol of root-knot nematode disease and plant pathogen (i.e., Chaetomium in NF, Xylari in GFL, and Microascus in PGA), heavy metal bioremediation (Hyphomacrobium in PGA and Xylaria in GFL), and nitrogen fixation (Nordella and Nitrospira in TF) was significantly increased; notably, potential harmful microflora, such as Plectosaphaerella and Rhizobacter, were more abundant in the control group. Conclusion: MI and GFL could improve the quality of P. quinquefolium by modifying its rhizosphere microbial community structure and composition, both of them are beneficial to the development of ecological cultivation of P. quinquefolium.
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Objective:To prove the effect of double V-Y procedure for paramedian tubercles plasty in patients with thin lower lips and dissatisfied appearance of lower lips.Methods:From 2013 to 2019, 127 Chinese cases of thin and dissatisfied appearance of lower lips were included. A double V-Y procedure for paramedian tubercles plasty was performed. Objective data of lip morphology before and after operation were measured, and subjective satisfaction survey and long-term follow-up were conducted.Results:The midline lower red lip height, the height of paramedian tubercles of lower-lip and the protrusion of lower-lip were significantly higher than that before the operation. The time of apocatastasis, scar softening of incision, natural expression recovery and local numbness relief were evaluated by following up at 7 d, and 3-24 months after operation, and it showed 73.2% of subjective satisfaction. The time of detumescence was 6-32 (15.2±3.5) days; the time of incision scar softening was 2-10 (5.1±2.3) months; the time of expression recovery was 1-7 (3.1±0.9) months; the time of numbness disappearance was 5 d-2 years (158.2±82.6) days.Conclusions:The double V-Y advancement of vermilion mucosa flap procedure for paramedian tubercles plasty displays a significant effect in improving volume and shape of lower lips. It is recommended for further clinical application.
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Objective:To observe and evaluate reductional M-shaped plasty method in patients with thick lips and dissatisfied lip appearance.Methods:From 2013 to 2019, 415 Chinese cases of thick upperlip without clear vermilion curve and tubercle were included. A reduction method for upper lip M-shaped plasty was performed. Objective data of lip morphology before and after operation were measured, and subjective satisfaction survey and long-term follow-up were conducted.Results:According to the statistics of 415 patients, the time of detumescence was 3-21 (11.8±2.6) days; the time of incision scar softening was 1-24 (2.6±0.8) months; the time of expression recovery was 1-24 (3.1±1.4) months; the time of numbness disappearance was 1-2 years. Three months after the operation, there was no significant change in the height of the central part of the upper red lip compared with that before the operation, the height of the red lip at the peak of the lip was significantly reduced, the height of the red lip was (13.3±2.2) mm before the operation, and (11.4±1.7) mm after the operation; the relative height of the dome point was significantly increased, the height was (0.4±1.0) mm before the operation, and the height was (2.1±0.5) mm after the operation. After more than 6 months of follow-up, patients' satisfaction rate of one operation was 72.0%, the satisfactory rate of upper lip shape was 75.4%, the long-term complications included obvious scars or discomfort (3.6%), local numbness (1.7%), and unnatural expression (0.7%).Conclusions:The reduction method for upper lip M-shaped plasty displays a significant effect in improving the shape of upper vermilion with thick and normal lips. The complications are slight and repairable. This lip cosmetology and rejuvenation procedure is recommended for further clinical application.
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Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested and cultivated resources during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.
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Objective:To explore the application of information management platform for Investigator Initiated clinical trials (IIT).Methods:Elaborate the design and application of Clinical Information Management Platform (CIMP). Discuss the obstacles in platform development.Results:Compared with regions where clinical research is more developed, there is still a lack of standardized and efficient information management methods in China. Through the construction of the IIT information management platform, the scientific management of the IIT and the SWOT analysis of the use of the platform have been conducted. Further exploration and improvement are needed in terms of the collaboration of the information platform, data standardization, and information sharing security.Conclusions:The management efficiency can be improved by applying CIMP, which will also promote the smooth implementation of IITs.
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Objective To analyze the pathogenic epidemiological characteristics of acute lower respiratory tract infection(ALRTI) in children in Gansu Province from 2012 to 2015. Methods The surveillance data of 458 children infected with ALRTI in 10 sentinel hospitals in Gansu province from 2012 to 2015 were collected, and infection status and epidemiological characteristics of each virus and bacteria were analyzed by descriptive study methods. Results The male to female ratio of the 458 children with ALRTI was 1.81:1, and the positive detection rate of the virus was 33.62%（95% CI：29.28%-37.97%), among which the positive detection rate of respiratory syncytial virus was the highest (12.23%).The positive detection rate of bacteria was 24.84%（95% CI：20.04%-29.65%),among which the positive detection rate of streptococcus pneumoniae was the highest (18.47%).There was significant no difference in the positive detection rate of virus and bacteria between children of different genders (P>0.05).There was significant no difference in the positive detection rate of virus among children of different age groups ( 2=5.980,P=0.050), but the positive detection rate of bacteria was different ( 2=12.078,P=0.002).Positive detection rates of virus infection and bacterial infection were different in distinct seasons (all P<0.05). By using logistics regression analysis, season, age and sentinel hospital were the influencing factors of ALRTI virus infection in children (all P<0.05), and sentinel hospital and years were the influencing factors of ALRTI bacterial infection in children (all P<0.05). Conclusion Respiratory syncytial virus, influenza virus and parainfluenza were the main causes of ALRTI virus infection in children aged 0-14 years in Gansu province, and the main bacterial infections were streptococcus pneumoniae and haemophilus influenzae, the number of virus infection was more than that of bacterial infection. Viral and bacterial infection had the same peak incidence.
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BACKGROUND@#Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.@*METHOD@#In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.@*RESULTS@#From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.@*CONCLUSION@#Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.
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Animals , Rats , Benzhydryl Compounds , Toxicity , Diethylstilbestrol , Toxicity , Dose-Response Relationship, Drug , Drug Interactions , Endocrine Disruptors , Toxicity , Estrogens , Toxicity , Models, Theoretical , Phenols , Toxicity , Rats, Sprague-Dawley , Risk AssessmentABSTRACT
Objective@#To evaluate the dietary exposure to deoxynivalenol (DON) from cereals and health risk in Chinese residents in different regions.@*Methods@#The data of DON concentration in cereals was derived from the national food safety risk surveillance from 2010 to 2017, with 15 422 samples of cereals included. China was roughly divided into north part and south part, along with the Qinling Mountains-Huaihe River line. Sample size of each type of cereals, i.e. wheat flour, maize meal, oats and rice was 4 948, 696, 626, 1 006 in the north, while 5 648, 1 068, 266, 1 164 in the south. The data of cereals consumption was derived from China National Nutrition and Health Survey in 2002 and 68 335 respondents aged 3 and above, with 34 234 from the north and 34 101 from the south, were included. Simple distribution model was applied for calculation and comparison of the dietary exposure to DON from cereals in northern and southern residents based on individual consumption of cereals, body weight and average DON concentration in each type of cereals.@*Results@#Average DON concentration in wheat flour, maize meal, oats, and rice sampled in northern China were 235.4, 121.6, 7.0 and 4.6 μg/kg, respectively, while 239.1, 124.3, 29.0 and 15.5 μg/kg in cereals sampled in southern China. The average DON exposure from cereals in surveyed Chinese inhabitants was 0.78 μg/(kg·d). Among them, the DON exposure of northern residents was higher than that of southern residents (P<0.001), and the average exposures were 1.15 and 0.41 μg/(kg·d), respectively. A total of 49.2% of northern residents exceeded provisional maximum tolerable daily intake for DON exposure from cereals, which was much higher than that of southern residents (8.6%) (P<0.001). Wheat-based food products were the main source of DON exposure, with a contribution rate of 96.5% in the north and 68.3% in the south. Average DON exposure was the highest in the 3-6 years [2.12 μg/(kg·d) for children in north and 0.73 μg/(kg·d) in south].@*Conclusion@#Exposure to DON from cereals in northern residents of China was considerably high, with a certain health risk. Northern children aged 3 to 6 exposed even more DON and needed significant attention.
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Objective@#To investigate the aluminium content in unprocessed grains from different areas of China.@*Methods@#From June 2013 to December 2014, nine provinces (Jilin, Shandong, Hubei, Hunan, Guangdong, Guangxi, Henan, Anhui and Jiangsu) were selected as sampling areas using stratified random sampling method. Three cities, counties or townships were randomly selected from each sampling area. Grain stations, grain depots, planting areas or farmers′ markets located in non-aluminium mining areas or non-aluminium-involved industrial pollution areas were selected from each sampling area using a purposive sampling method. A total of 470 unprocessed grain samples (500 g per sample) including wheat, rice, corn, millet and soybean were collected from local grain stations, grain depots, planting areas and farmers′ markets. The dried grains samples were analysed for aluminium content by inductively coupled plasma mass spectrometry. Bootstrap resampling method was applied to calculate the upper bound values of 95%CI of P99 of aluminium contents for each kind of grain, which could be regarded as levels of concern for corresponding categories.@*Results@#A total of 454 grain samples, including 109 wheat samples, 111 rice samples, 78 corn samples, 69 millet samples and 87 soybean samples, were used for analysis after excluding outlier values. There were 420 positive samples with detected aluminium and the overall detection rate was 92.5%. Among them, the aluminium contents were high in wheat and soybean with median values about 9.59 and 7.12 mg/kg, and maximum values about 31.55 and 28.80 mg/kg, respectively. The median and maximum values of aluminium contents in corn were about 4.65 and 26.79 mg/kg. Aluminium contents were low in rice and millet, with median values about 1.49 and 2.21 mg/kg, and maximum values about 7.56 and 8.07 mg/kg, respectively. Based on Bootstrap resampling method, the upper bound values of 95%CI of P99 of aluminium contents in wheat, soybean, corn, rice and millet were 29.86, 28.80, 26.79, 7.56 and 8.07 mg/kg, respectively, which could be regarded as levels of concern for corresponding grains.@*Conclusion@#Aluminium has been detected in most unprocessed grains. The accumulation of aluminium varies in different grains species.
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Objective With the fast development of Investigator-Initiated Trials (IIT),more and more resources from the national and local governments,universities and hospitals were invested.It is important to clarify the content and methodologies of quality evaluation of the IITs at the early approval stage to assure more complete and systematic quality assessment,improve resource allocation,enhance the research ability,as well as the protection of human subject.Methods This article summarized the content and related safeguarding measures of quality assessment during the early stage of project setup.Discussed relative practice and experiences of our center.Results The contents of quality evaluation include research topic,study protocol,research team and qualifications,quality assurance plan and risk management.The organizing work and attention of the research administrative department,qualified departments and experts,as well as information platform are the required safeguarding measures for effective assessment.Conclusions Quality evaluation of IITs at the early approval stage is critical segment of study quality assurance.More attention should be paid to make every effort counts.
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Objective: To observe the effect of serum-containing Qingxin Tongmai decoction(QXTMD) on the apoptosis rate of mouse mononuclear macrophage cell line RAW264.7 induced by Acetylated low density lipoprotein (ac-LDL) and the expressions of type A scavenger receptor(SR-A), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), inositol-requiring enzyme 1α(IRE1α), exploring the possible mechanism of QXTMD in the treatment of atherosclerosis.Method: Eight New Zealand rabbits were randomly divided into the atorvastatin group (2.6 g·kg-1) low, medium and high-dose QXTMD groups (3.33, 6.66, 13.32 mg·kg-1). After 7 days of gavage, the carotid blood was collected to prepare drug-containing serum. The RAW264.7 cell line was stimulated with 2.5%, 5%, 10%, and 20% drug-containing serum culture for 6, 12, and 24 h, respectively. The cell proliferation rate was observed by cell counting kit-8 (CCK-8) method. The RAW264.7 cell line was cultured in vitro and divided into blank group, model group, atorvastatin group, and low, medium and high-dose QXTMY groups. The cells in blank group were cultured with bovine serum albumin(BSA). The model group was stimulated with BSA+50 mg·L-1 ac-LDL for 24 h. The other groups were stimulated with BSA+50 mg·L-1 ac-LDL+10% drug-containing serum for 24 h. The apoptosis rate and SR-A expression of RAW264.7 cells were detected by flow cytometry. The expressions of Bcl-2, Bax and IRE1α protein were detected by Western blot.Result: Compared with the blank group, the model group could increase the apoptosis rate of RAW264.7 cells (PPPPα (PPPPPConclusion: QXTMD can reduce the apoptosis rate of macrophages. The mechanism of atherosclerosis may be related to the expressions of Bax, IREα, SR-A and anti-apoptotic protein Bcl-2.
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TIMMDC1 (C3orf1), a predicted 4-pass membrane protein, which locates in the mitochondrial inner membrane, has been demonstrated to have association with multiple member of mitochondrial complex I assembly factors and core mitochondrial complex I subunits. The expression level of TIMMDC1 in highly-metastatic tumor cells is higher than that in lowly- metastatic tumor cells. However, the role of TIMMDC1 in human gastric cancer progression is unclear. In this study, human gastric cancer cells SGC-7901 and BGC-823 cells were used, and TIMMDC1 was knockdown with small interfering RNA. The data showed that TIMMDC1 knockdown caused inhibitory effects on the cell proliferation in vitro and tumor progression in vivo. Knockdown of TIMMDC1 significantly and exclusively reduced the activity of mitochondrial complex I but not complex II~ IV, and caused an obvious inhibition in mitochondrial respiration and ATP-linked oxygen consumption. Besides, the glycolysis pathway was also attenuated by TIMMDC1 knockdown, and the ATP content in the group of shTIMMDC1 cells was significantly lower than that in the shCont cells. The expression levels of phosphoylated AKT(Ser473) and GSK-3ß (Ser9), as well as the downstream protein ß-catenin and c-Myc were also markedly reduced in the group of shTIMMDC1 cells. Taken together, these findings suggest that TIMMDC1 may play an important role in human gastric cancer development, and its underlying mechanism is not only associated with mitochondrial complex I inhibition and reduced mitochondrial respiration, but is also associated with reduced glycolysis activity and the AKT/GSK3ß/ß-catenin signaling pathways.
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Glycogen Synthase Kinase 3 beta/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/metabolism , beta Catenin/metabolism , Animals , Blotting, Western , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Gene Expression Regulation, Neoplastic/genetics , Glycogen Synthase Kinase 3 beta/genetics , Glycolysis/genetics , Glycolysis/physiology , Humans , Male , Mice , Mice, Nude , Mitochondrial Membrane Transport Proteins/genetics , Mitochondrial Precursor Protein Import Complex Proteins , Proto-Oncogene Proteins c-akt/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction/genetics , Signal Transduction/physiology , Stomach Neoplasms/genetics , Wound Healing/genetics , Wound Healing/physiology , beta Catenin/geneticsABSTRACT
BACKGROUND@#China has the world's largest tea plantation area in the world. To sustain high yields of the tea, multiple pesticides are used on tea crops to control pests. Organophosphorus (OP) pesticides are among the most widely used types of agricultural pesticides in China. As tea is a significant potential source of exposure to pesticide residues, the public concern has increased in relation to pesticide residues found in tea in China. The aim of the study was to estimate cumulative dietary exposure to OP residues from tea infusion for Chinese tea consumers to determine whether exposure to OP residues from tea infusion is a cause of health concern for tea consumers in China.@*METHODS@#OP residue data were obtained from the China National Monitoring Program on Food Safety (2013-2014), encompassing 1687 tea samples from 12 provinces. Tea consumption data were obtained from the China National Nutrient and Health Survey (2002), comprising 506 tea consumers aged 15-82 years. The transfer rates of residues from tea leaves into tea infusions were obtained from the literature. The relative potency factor (RPF) approach was used to estimate acute cumulative exposure to 20 OP residues from tea infusion using methamidophos as the index compound. Dietary exposure was calculated in a probabilistic way.@*RESULTS@#For tea consumers, the mean and the 99.9th percentile (P99.9) of cumulative dietary exposure to OP residues from tea infusion equalled 0.08 and 1.08 μg/kg bw/d. When compared with the acute reference dose (ARfD), 10 μg/kg bw/d for methamidophos, this accounts for 0.8 and 10.8% of the ARfD.@*CONCLUSIONS@#Even when considering OP residues from vegetables, fruits and other foods, there are no health concerns based on acute dietary exposure to OP residues from tea infusion. However, it is necessary to strengthen the management of the OP pesticides used on tea in China to reduce the risk of chronic dietary exposure to OPs from tea infusion.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , China , Dietary Exposure , Organophosphorus Compounds , Pesticide Residues , Risk Assessment , Methods , Tea , ChemistryABSTRACT
Objective:To evaluate the effects of amelogenin(AML)on the migration,adhesion and proliferation of periodontal liga-ment stem cells(PDLSCs).Methods:PDLSCs were cultured with AML at 0.25,50 amd 100 μg/ml respectively.The migration, adhesion and proliferation of the cells were examined by wound healing migration assay,transwell migration assay,attachment assay, MTT assay and cell counting,respectively.Results:AML induced the migration of PDLSCs in a dose-dependent manner(P <0.05), increased the adhesion and proliferation of PDLSCs(P <0.05).Conclusion:AML may promote the migration,adhesion and prolifer-ation of PDLSCs.
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Objective:To determine the mechanism of sunitinib-induced autophagy in renal cell carci-noma cells.Methods:MTS assay was applied to detect the cell viability alteration under the treatment of sunitinib (2,8 μmol /L).The sunitinib-induced autophagy as well as cell apoptosis was measured and compared after knocking down autophagy-related protein Beclin1 and microtubule associated protein 1 light chain 3 fusion protein (LC3)by RNA interference.The transmission electron microscope was used to observe the formation of autophagosomes in ACHN cells.The fluorescence microscope was used to mo-nitor distribution and aggregation of endogenous LC3-Ⅱ.The expressions of protein such as LC3-Ⅱ,the autophagic regulation molecules protein kinase B /mammalian target of rapamycin (Akt/mTOR)and the symbol of apoptosis poly ADP-ribose polymerase (PARP)were capable to be detected by immunoblotting assay.Results:Sunitinib was able to significantly trigger cell viability loss in the renal carcinoma cell ACHN,which was both in a concentration-dependent and time-dependent manner (P <0.05 ).After reducing the autophagy by knocking down Beclin1 and LC3,the number of cleavage of PARP was in-creased remarkably,whereas there was nearly not any cleavage in the mock group.By the transmission electron microscope,there were more autophagic vacuoles in ACHN cells after being administrated with sunitininb compared with the control.And the nuclear-to-cytosol translocation as well as aggregation of LC3-Ⅱ was presented after sunitinib treatment by the fluorescence microscope,which was the proof of the enhanced autophagy.According to the immunoblotting,sunitinib was able to increase the accumula-tion of LC3-Ⅱ.At the same time,the result of sunitinib combined with chloroquine,a drug which blocked the fusion of autophagosomes and lysosomes,demonstrated that the increasing amount of LC3-Ⅱwas due to the enhanced autophagy flux by sunitinib treatment in ACHN cells.However,phosphorylation of Akt as well as mTOR was decreased at the same time.The rapamycin (mTOR inhibitor)or knocking down Akt subunits could change the sunitinib-induced LC3-Ⅱ accumulation,whereas overexpression of Akt subunits decreased the autophagic flux,indicating that Akt/mTOR was the target of sunitinib in auto-phagy.Conclusion:Sunitinib induced autophagy via suppressing Akt/mTOR pathway,and the auto-phagy was involved in apopotosis.