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The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.
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To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.
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Tamoxifen resistance is a major roadblock in the treatment of patients with breast cancer. Ribonucleotide reductase M2 (RRM2) was found to be involved in acquired resistance of breast cancer cells (BCCs) to tamoxifen. Here, we used GW8510, which has been identified as a potential RRM2 inhibitor, to evaluate the effect of RRM2 inhibition on reversing resistance of BCCs to tamoxifen and investigate its mechanisms. We showed that RRM2 overexpression played a key role in the development of acquired tamoxifen resistance in BCCs through downregulation of autophagy level. Combination treatment with tamoxifen and GW8510 significantly inhibited survival of the tamoxifen-resistant BCCs through induction of autophagic cell death compared to either of the two drugs. Furthermore, combination of tamoxifen and GW8510 resulted in marked growth inhibition of tamoxifen-resistant BBC xenograft tumor in vivo compared to tamoxifen or GW8510 alone. In conclusion, tamoxifen in combination with GW8510 can overcome acquired tamoxifen resistance in BCCs and may be a rational therapeutic approach against breast cancer with high RRM2 expression.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Breast Neoplasms/drug therapy , Indoles/pharmacology , Ribonucleoside Diphosphate Reductase/metabolism , Tamoxifen/pharmacology , Animals , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Autophagy/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Down-Regulation , Drug Resistance, Neoplasm , Drug Synergism , Female , Humans , Indoles/administration & dosage , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Ribonucleoside Diphosphate Reductase/antagonists & inhibitors , Tamoxifen/administration & dosage , Xenograft Model Antitumor AssaysABSTRACT
Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild-type is intrinsic resistance to EGFR-tyrosine kinase inhibitors (TKIs). In this study, we assessed whether the combination of bisdemethoxycurcumin (BDMC) and icotinib could surmount primary EGFR-TKI resistance in NSCLC cells and investigated its molecular mechanism. Results showed that the combination of BDMC and icotinib produced potently synergistic growth inhibitory effect on primary EGFR-TKI-resistant NSCLC cell lines H460 (EGFR wild-type and K-ras mutation) and H1781 (EGFR wild-type and Her2 mutation). Compared with BDMC or icotinib alone, the two drug combination induced more significant apoptosis and autophagy via suppressing EGFR activity and interaction of Sp1 and HDCA1/HDCA2, which was accompanied by accumulation of reactive oxygen species (ROS), induction of DNA damage, and inhibition of cell migration and invasion. ROS inhibitor (NAC) and autophagy inhibitors (CQ or 3-MA) partially reversed BDMC plus icotinib-induced growth inhibitory effect on the NSCLC cells. Meanwhile, co-treatment with NAC attenuated the two drug combination-induced autophagy, apoptosis, DNA damage and decrease of cell migration and invasion ability. Also, 3-MA or CQ can abate the combination treatment-induced apoptosis and DNA damage, suggesting that there is crosstalk between different signaling pathways in the effect produced by the combination treatment. Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Crown Ethers/therapeutic use , Diarylheptanoids/therapeutic use , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Animals , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/drug effects , DNA Damage , Drug Resistance, Neoplasm/drug effects , Drug Synergism , ErbB Receptors/antagonists & inhibitors , Histone Deacetylase Inhibitors/therapeutic use , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Reactive Oxygen Species/metabolism , Sp Transcription Factors/antagonists & inhibitors , Voltage-Dependent Anion Channel 1/antagonists & inhibitorsABSTRACT
Multiemissive sensors are being actively pursued, because of their ratiometric luminescent detection capabilities, which demonstrates better sensitivity and selectivity than conventional single-emission sensors. Herein, we present a trichromatic white-light-emitting metal-organic framework (MOF) composite (Z3) by simultaneously incorporating red/green-emitting Pt/Ru complex cations into porous blue-emitting bio-MOF-1 through post-synthetic modification. With the help of a three-dimensional (3-D) dual-ratiometric luminescence recognition method, and unique turn-on responses of the red emission toward amine compounds (ACs), including NH3 and aliphatic amines, via confinement-induced luminescence enhancement effect, Z3 can work as a dual-ratiometric luminescent sensor for discrimination of 7 out of 11 AC vapors. This work not only provides a new AC sensing mechanism (confinement effect) that can induce a "turn-on" response but also proves that the accuracy and selectivity of composite sensor can be greatly improved through the combination of 3-D recognition method and the confinement effect. Thus, it open up fresh opportunities to develop composite sensors with excellent sensing and differentiating ability.
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BACKGROUND: Although mesenchymal stem cells (MSCs) and MSCs-released exosomes are expected to become a new means for osteoarthritis, the concrete molecular mechanisms remain unclear yet. OBJECTIVE: To understand the effect and mechanism of exosomes in the MSC treatment of osteoarthritis based on the main pathogenesis of osteoarthritis and characteristics of MSCs. METHODS: Domestic and foreign articles concerning MSCs and MSCs-released exosomes for the osteoarthritis treatment published from 2006 to 2016 were retrieved and analyzed. The keywords used were "exosomes, mesenchymal stem cells, osteoarthritis" in Chinese and English, respectively. RESULTS AND CONCLUSION: Osteoarthritis is a refractory disease associated with age and strain, and MSCs therapy has been obtained a good effect. Cartilage differentiation, microenvironment improvement, paracrine and exosomes mechanism of MSCs have also been reported. Exosomes play an important role in mediating intercellular signal transduction and biological responses by transferring a variety of biologically active proteins, lipids, nucleic acids and other molecules. The changes are not only related to the osteoarthritis pathogenesis, but also involved in MSCs induced regeneration and repair of bone and joint tissues. Exosomes secreted by MSCs can improve bone and joint tissue regeneration through membrane exchange and transport of active molecules. This will provide a new insight into the osteoarthritis treatment.
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In order to provide reference for development of the new curriculum for graduate students "The principle,technical and clinical practice of stem cell" and improve the quality of teaching and learning,we summarized some experiences and lessons for this course.This paper introduced some measures and achievements on the teaching reform from several aspects including curriculum design,selection of teaching content,teaching idea and mode,training the teaching groups and so on.Moreover,it especially emphasized that teaching contents should not only pay attention to the basic and clinical application,but also combine the present laws and keep abreast of scientific and technological developments.In the process of teaching,we need to value the quality of teachers and improve teaching standards,meanwhile we should pay attention to the culture of thought and the capacity of innovation,stimulating students' interests in studies,improving autonomous study and practices ability through multiple means and channels.This course teaching got satisfactory results and the acquired practice experiences were worth of being popularized in the further graduate students teaching.
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Objective To investigate the application of band to strengthen core stability training for cerebral palsy. Methods From May, 2015 to December, 2016, 70 children with spastic cerebral palsy in outpatient department were di-vided into control group (n=35) and observation group (n=35). Both groups accepted routine rehabilitation train-ing, and the control group accepted core stability training, while the observation group was trained with a band during core stability training, for twelve weeks. They were assessed with Gross Motor Function Measure- 88 (GMFM-88), Berg Balance Scale (BBS), Manual Muscle Test (MMT) before and after treatment. Results The scores of GMFM- 88, BBS and MMT of external oblique improved in both groups after treatment (t>12.904, P<0.001), and improved more in the observation group than in the control group (t>2.121, P<0.05). Conclusion Strengthening core stability training with a band can further improve gross motor function, balance and mus-cle strength in the spastic cerebral palsy children.
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Hematopoietic stem cells(HSCs)senescence is an important reason of hematopoietical and immunologi-cal function senescence.It also is play a key role during aging-related diseases development.Under certain condi-tions,the activation of classical Wnt 3a/β-catenin is in favour of maintains polarity and young states of HSCs,self-renewing,proliferation and differentiation potency.Switching to the non-classical Wnt5a pathway,further activation of Cdc42 protein and others can promote HSCs ageing,and indirectly inhibits Wnt3a/beta-catenin pathway.The in-tervention of two Wnt signaling pathways switching and mechanism,not only can illustrate the mechanism of HSCs aging,but also clear how to slow down ageing.This could provide a new strategy on the solution of age-related dis-eases and keeping a young state.
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The combination of platinum and gemcitabine is one of the standard regimens in the treatment of advanced lung squamous carcinoma (LSC). Resistance to gemcitabine is main barrier to the successful treatment of LSC. In this study, we showed that suppression of the Fanconi anemia (FA) pathway increased the sensitivity of two LSC cell lines SK-MES-1 and KLN205 to gemcitabine. Moreover, we found that the CHK1 pathway and the FA pathway are functionally compensatory in the repair of DNA damage in the LSC cell lines. Inactivation of one of the two pathways led to DNA damage, triggering compensatory activation of other pathway. Furthermore, we demonstrated that FANCD2 depletion combined with CHK1 inhibitor MK-8776 significantly potentiated the cytotoxicity of gemcitabine to the two LSC cell lines, compared to individual FANCD2 depletion or MK-8776 treatment. The enhanced effect of gemcitabine-chemosensitization was accompanied by loss of DNA repair function and accumulation of DNA single strand breaks and double strand breaks, in parallel with obvious increase of caspase-3 dependent apoptosis. Our results indicate that the enhancement effect of FANCD2 depletion combined with CHK1 inhibitor in sensitizing the LCS cells to gemcitabine supports the FA pathway and CHK1 as two therapeutic targets for improvement of anti-tumor regimens in treatment of LSC.
Subject(s)
Checkpoint Kinase 1/antagonists & inhibitors , Deoxycytidine/analogs & derivatives , Fanconi Anemia Complementation Group Proteins/metabolism , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Signal Transduction/drug effects , A549 Cells , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Checkpoint Kinase 1/metabolism , Deoxycytidine/pharmacology , Drug Synergism , Fanconi Anemia Complementation Group Proteins/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , RNA Interference , Signal Transduction/genetics , GemcitabineABSTRACT
Human schistosomiasis, caused by Schistosoma species, is a major public health problem affecting more than 700 million people in 78 countries, with over 40 mammalian host reservoir species complicating the transmission ecosystem. The primary cause of morbidity is considered to be granulomas induced by fertilized eggs of schistosomes in the liver and intestines. Some host species, like rats (Rattus norvegicus), are naturally intolerant to Schistosoma japonicum infection, and do not produce granulomas or pose a threat to transmission, while others, like mice and hamsters, are highly susceptible. The reasons behind these differences are still a mystery. Using inducible nitric oxide synthase knockout (iNOS-/-) Sprague-Dawley rats, we found that inherent high expression levels of iNOS in wild-type (WT) rats play an important role in blocking growth, reproductive organ formation, and egg development in S. japonicum, resulting in production of nonfertilized eggs. Granuloma formation, induced by fertilized eggs in the liver, was considerably exacerbated in the iNOS-/- rats compared with the WT rats. This inhibition by nitric oxide acts by affecting mitochondrial respiration and energy production in the parasite. Our work not only elucidates the innate mechanism that blocks the development and production of fertilized eggs in S. japonicum but also offers insights into a better understanding of host-parasite interactions and drug development strategies against schistosomiasis.
Subject(s)
Host-Parasite Interactions , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide , Schistosoma japonicum/growth & development , Adoptive Transfer , Animals , Cell Respiration , Female , Male , Mice, Inbred BALB C , Nitric Oxide Synthase Type II/genetics , Rats, Sprague-Dawley , Schistosoma japonicum/metabolismABSTRACT
Cisplatin exert its anticancer effect by creating intrastrand and interstrand DNA cross-links which block DNA replication and is a major drug used to treat lung cancer. However, the main obstacle of the efficacy of treatment is drug resistance. Here, we show that expression of translesion synthesis (TLS) polymerase Q (POLQ) was significantly elevated by exposure of lung cancer cells A549/DR (a cisplatin-resistant A549 cell line) to cisplatin. POLQ expression correlated inversely with homologous recombination (HR) activity. Co-depletion of BRCA2 and POLQ by siRNA markedly increased sensitivity of A549/DR cells to cisplatin, which was accompanied with impairment of double strand breaks (DSBs) repair reflected by prominent cell cycle checkpoint response, increased chromosomal aberrations and persistent colocalization of p-ATM and 53BP1 foci induced by cisplatin. Thus, co-knockdown of POLQ and HR can efficiently synergize with cisplatin to inhibit A549/DR cell survival by inhibiting DNA DSBs repair. Similar results were observed in A549/DR cells co-depleted of BRCA2 and POLQ following BMN673 (a PARP inhibitor) treatment. Importantly, the sensitization effects to cisplatin and BMN673 in A549/DR cells by co-depleting BRCA2 and POLQ was stronger than those by co-depleting BRCA2 and other TLS factors including POLH, REV3, or REV1. Our results indicate that there is a synthetic lethal relationship between pol θ-mediated DNA repair and HR pathways. Pol θ may be considered as a novel target for lung cancer therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA-Directed DNA Polymerase/metabolism , Drug Resistance, Neoplasm/genetics , Homologous Recombination/drug effects , Lung Neoplasms/genetics , Cell Line, Tumor , Cell Survival , Cisplatin/pharmacology , DNA Damage/drug effects , DNA Repair/drug effects , Homologous Recombination/genetics , Humans , DNA Polymerase thetaABSTRACT
PURPOSE: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. RESULTS: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. CONCLUSION: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.
Subject(s)
Animals , Rabbits , Blood Cells/cytology , Bone Morphogenetic Protein 2/genetics , Cell- and Tissue-Based Therapy , Femur Head Necrosis/metabolism , Gene Expression Regulation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Osteonecrosis/pathology , PPAR gamma/genetics , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To explore the effective method for enrichment of rat peripheral blood-derived mesenchymal stem cells(PBMSC) and study the cell biological characteristics.</p><p><b>METHODS</b>Peripheral mononuclear cells were isolated by density gradient centrifugation from blood of 4 week old rats after G-CSF mobilization. Thereafter, the fibroblast-like cells were acquired by plastic-adherent culture, and the proliferation curve was assayed. For analyzing surface markers of the second generation cultured isolated PBMSC, both flow cytometry(CD90, CD44, CD29, CD45, CD11b and CD79a) and immunocytochemical staining(CD73, CD105, CD34 and HLA-DR) methods were used. Furthermore, the differentiation capacities of PBMSC into osteocytes, chondrocytes and adipocytes were identified.</p><p><b>RESULTS</b>(1) The adherent cells displayed typical colony-forming unit fibroblast(CFU-F) growth pattern after 6-7 day of primary culture and reached 80% confluence after 21 days of culture. The passaged PBMSC possessed high proliferative capacity and spindle growth pattern and was able to grown into exponential phase next day with a doubling time of 39.2 h. (2) PBMSC expressed mesenchymal markers such as CD90, CD44, CD29, CD73 and CD105, but failed to expressed markers of CD45, CD11b, CD79a, CD34 and HLA-DR. (3) After 21 days of culture in osteogenic, chondrogenic and adipogenic differentiation media, calcifying nodules, intracellular glycosaminoglycans and lipid droplets could be found by alizarin red, alcian blue and oil red-O staining, respectively.</p><p><b>CONCLUSION</b>PBMSC can be enriched from rat peripheral blood with high purity and abundance by our methods. The growth and phenotypic characteristics of the isolated PBMSC are consistent with that of well-known MSC, and these cells possess the capability to multi-lineage mesoderm differentiation.</p>
Subject(s)
Animals , Rats , Adipocytes , Cell Differentiation , Cells, Cultured , Chondrocytes , Flow Cytometry , Mesenchymal Stem Cells , OsteocytesABSTRACT
OBJECTIVE: Lifestyle changes have led to an increasing incidence of acute pancreatitis (AP) in China. The aims of this study were to evaluate the association between lifestyle as well as medical history and AP in the elderly population and to provide evidence towards the prevention against AP. METHODS: A population-based cross-sectional study was conducted in Daqing, Heilongjiang Province, China. A total of 23 294 residents aged ≥55 years were enrolled in the study. A questionnaire survey was conducted to collect data on participants' characteristics, lifestyle and medical history via a face-to-face interview, and compared these data with the medical chart. RESULTS: In total, 45 participants had been diagnosed with AP, that is, a prevalence of 0.19%. No significant differences were observed with respect to their age, gender, marital status or body mass index (BMI) in participants with and without AP. However, those were better educated were more likely to develop AP (P = 0.005). The univariate analysis showed that a high meat intake, smoking, alcohol consumption and a medical history of gallstones were associated with a significant increase in the risk of developing AP (P < 0.05). Furthermore, smoking or alcohol consumption was dose-dependently associated with the risk of AP, particularly in those who smoked at least 15 pack-years or consumed ≥56.2 drinks per year. Multivariable logistics analysis suggested that the level of education, smoking and medical history of gallstone are independent risk factors for AP. CONCLUSIONS: Our study indicated that a higher education level, smoking, alcohol consumption and history of gallstones may be potential risk factors for AP in the elderly in northeast China.
Subject(s)
Pancreatitis/etiology , Acute Disease , Age Distribution , Aged , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , China/epidemiology , Cross-Sectional Studies , Diet/adverse effects , Diet/statistics & numerical data , Female , Gallstones/complications , Gallstones/epidemiology , Humans , Life Style , Male , Middle Aged , Pancreatitis/epidemiology , Risk Factors , Sex Distribution , Smoking/adverse effects , Smoking/epidemiologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin II (Ang II)-induced proliferation in cultured rat vascular smooth muscle cells (VSMCs).</p><p><b>METHODS</b>VSMCs were isolated from Male Sprague-Dawley rat aorta, and cultured by enzymic dispersion method. Experiments were performed with cells from passages 3-8. The cultured VSMCs were randomly divided into control, model (Ang II 0.1 μmol/L), and rutaecarpine (0.3-3.0 μmol/L) groups. VMSC proliferation was induced by Ang II, and was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and cell counting. To examine the mechanisms involved in anti-proliferative effects of rutaecarpine, nitric oxide (NO) levels and NO synthetase (NOS) activity were determined. Expressions of VSMC proliferation-related genes including endothelial nitric oxide synthase (eNOS), and c-myc hypertension related gene-1 (HRG-1) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Rutaecarpine (0.3-3.0 μmol/L) inhibited Ang II-induced VSMC proliferation and the best effects were achieved at 3.0 μmol/L. The Ang II-induced decreases in cellular NO contents and NOS activities were antagonized by rutaecarpine (P <0.05). Ang II administration suppressed the expressions of eNOS and HRG-1, while increased c-myc expression (P <0.05). All these effects were attenuated by 3.0 μmol/L rutaecarpine (P <0.05).</p><p><b>CONCLUSION</b>Rutaecarpine is effective against Ang II-induced rat VSMC proliferation, and this effect is due, at least in part, to NO production and the modulation of VMSC proliferation-related gene expressions.</p>
Subject(s)
Animals , Male , Rats , Angiotensin II , Pharmacology , Base Sequence , Cell Proliferation , Cells, Cultured , DNA Primers , Hemeproteins , Metabolism , Indole Alkaloids , Pharmacology , Muscle, Smooth, Vascular , Cell Biology , Nitric Oxide Synthase Type III , Metabolism , Proto-Oncogene Proteins c-myc , Metabolism , Quinazolines , Pharmacology , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms.</p><p><b>METHODS</b>The 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence.</p><p><b>RESULTS</b>Compared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01).</p><p><b>CONCLUSION</b>WLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.</p>
Subject(s)
Animals , Female , Male , Rats , Antiporters , Metabolism , Bicarbonates , Metabolism , Cystic Fibrosis Transmembrane Conductance Regulator , Metabolism , Drugs, Chinese Herbal , Pharmacology , Gastric Mucosa , Metabolism , Rats, Sprague-Dawley , Stomach Ulcer , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the CD phenotypic, protein expression and pluripotent differentiation of human hypertrophic scar fibroblasts cultured in vitro, so as to study the mechanisms of scar formation.</p><p><b>METHODS</b>Fibroblasts were isolated and cultured from human hypertrophic scar of 3 cases. The cells morphology was observed by inverted microscope, and the growing state of the third passage was detected by the cell counting meter of Vi-CELL. The cell surface markers CD105, CD14, CD73, CD34, CD44, CD45 and CD90 were identified by flow cytometry. The expression of CK19, Oct-4, Nanog and vimentin was detected by immunocytochemistry, and the expression of alpha-smooth muscle actin(alpha-SMA) was tested by immunofluorescence. The differentiated potential of fibroblasts of the third passage into adipogenic, osteogenic and chondrogenic lineages was assayed.</p><p><b>RESULTS</b>The primary passage fibroblasts showed the shape of spindle shaped or irregular polygon with a radiated or circinate of growing arrangement. The growth curve showed the cells growth was slow on the first and second day, and quick during the third to fifth day, which reached platform stage on the sixth or seventh day. The fibroblasts highly expressed mesenchymal stem cell surface markers-CD73, CD105, CD44, CD90, but not expressed hematopoietic stem cell surface markers-CD14, CD34, CD45 by flow cytometry. And positive expression of vimentin, Oct-4 and negative expression of CK19 were detected by Immunocytochemistry. Positive expression of alpha-SMA was also detected by immunofluorescence. Multidirectional differentiation induction indicated that the third passage cells could differentiate into adipogenic, osteogenic and chondrogenic lineages.</p><p><b>CONCLUSIONS</b>Human hypertrophic scar-derived fibroblasts show the biologic characteristics of mesenchymal stem cells, which may play an important role in wound healing and hypertrophic scar formation.</p>
Subject(s)
Adolescent , Female , Humans , Male , Young Adult , Antigens, CD , Metabolism , Cell Differentiation , Physiology , Cells, Cultured , Cicatrix, Hypertrophic , Pathology , Fibroblasts , Cell Biology , Metabolism , Mesenchymal Stem Cells , Cell Biology , Metabolism , PhenotypeABSTRACT
<p><b>OBJECTIVE</b>To investigate the differentiation of human amniotic epithelial cells (hAECs) into insulin secreting cells (ISCs) in vitro.</p><p><b>METHODS</b>The hAECs were isolated from human amnion by trypsin digestion, and the phenotype of the isolated cells were identified by flow cytometry and immunocytochemical staining. The hAECs at passage 3 were treated with nicotinamide and N2 supplement to investigate their differentiation into ISCs. At different times after differentiation, the expression of insulin and beta2 microglobulin (beta2-MG) was determined by immunocytochemical staining, while the content of insulin in supernatant from cultured hAECs was detected by radioimmunoassay and the expressions of insulin, pancreatic and duodenal homeobox factor-1 (PDX-1) mRNA were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>(1) hAECs expressed high percent of CD29, CD73, CD166 and CK19. (2) At 7, 14 and 21 days, the percentages of insulin-positive cells in induced groups were 74.00% +/- 1.73%, 75.33% +/- 1.15% (see symbol) 75.67% +/- 0.58% respectively, which were negative in control groups. (3) At 7, 14 and 21 days, contents of insulin in supernatant from induced groups were (328.47 +/- 3.22) microIU/ml, (332.26 +/- 1.22) microIU/ml and (329.68 +/- 2.57) microIU/ml respectively, they were significantly higher than those in control groups (All P < 0.01). (4) PDX-1 mRNA and beta2-MG were expressed before and after the induction of hAECs, but insulin mRNA was expressed only in the induced groups.</p><p><b>CONCLUSION</b>hAECs can differentiate into ISCs, having the potential application for therapy of type I diabetes.</p>
Subject(s)
Humans , Amnion , Cell Biology , Cell Culture Techniques , Cell Differentiation , Physiology , Cells, Cultured , Epithelial Cells , Cell Biology , Flow Cytometry , Homeodomain Proteins , Metabolism , Insulin , Metabolism , Insulin-Secreting Cells , Cell Biology , RNA, Messenger , Genetics , Trans-Activators , Metabolism , beta 2-Microglobulin , MetabolismABSTRACT
OBJECTIVE: To establish a mouse model of abdominal aorta stenosis and analyze the alterations in the arterial wall response to high and low shear stress. METHODS: Twenty mouse were randomized equally into 4 groups, including 3 test groups (1, 7 and 14 day groups) with surgically induced stenosis of the abdominal aorta, and a sham-operated group without stenosis. The hemodynamics and the internal diameter of the blood vessel were measured by color Doppler flow imaging. The wall shear stress was calculated by Poiseiulle hydrodynamics formula (τ(m)=η×4×V(m)/D). Pathological examination and immunohistochemistry were performed to observe the arterial morphological changes and the endothelial vascular cell adhesion molecule-1 (VCAM-1) expression. The intimal-media thickness of the aorta was measured and endothelial VCAM-1 expression analyzed quantitatively. RESULTS: Regions of low and high flow shear stress were created upstream from the stenosis and within the stenosis, respectively. Compared with the sham-operated group, the mice with aorta stenosis showed gradually increased vascular intimal-media thickness and VCAM-1 expression intensity in the upstream aorta, but not within the regions of the stenosis. CONCLUSION: Vascular remodeling may occur shortly after exposure to low shear stress, which plays a significant role in initiation and progression of the pathological process of atherosclerosis mediated by VCAM-1, whereas high shear stress may exert an anti-atherosclerotic effect.