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Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by chronic progressive bile duct inflammation and has a low incidence rate and poor prognosis in China. There is still no drug therapy that can change the course of PSC, and liver transplantation is the only effective treatment for PSC, with a 5-year survival rate of 85% after transplantation. Drug therapy for PSC is facing great challenges based on the current status of PSC. At present, drugs for the treatment of PSC are in the stage of clinical trials and have shown certain application prospect, among which ursodeoxycholic acid is the most widely studied and commonly used drug. In addition, there are many emerging drugs in the pipeline. This article summarizes the latest advances in drug therapy for PSC.
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Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
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Animals , Rabbits , Atrial Fibrillation/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Signal Transduction , NF-E2-Related Factor 2/pharmacology , Molecular Docking Simulation , Oxidative Stress , Energy Metabolism , Mitochondria/metabolism , Inflammation/metabolism , Heme Oxygenase-1ABSTRACT
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.
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OBJECTIVE@#To investigate the mutational spectrum and its prognostic significance in patients with acute myeloid leukemia (AML).@*METHODS@#The clinical data of 93 patients with newly diagnosed AML who underwent gene mutation detection by high-throughput sequencing (HTS) from March 2014 to April 2018 in our hospital was analyzed retrospectively. The distribution of mutant genes was summarized and the prognostic factors for intermediate-risk acute myeloid leukemia (IR-AML) were analyzed.@*RESULTS@#Among 93 AML patients, 88.17% had at least one gene mutation, and 53.76% patients showed more than one recurrent genetic mutation. CEBPA showed the highest mutation frequency (20.4%), followed by ASXL1, TET2, NRAS, FLT3-ITD, NPM1, IDH2, DNMT3A, and their mutation frequency were higher than 10%. IDH1/2 and NPM1, ASXL1 and U2AF1, FLT3 and NPM1 often co-occured (P 100×10@*CONCLUSION@#There are co-occurring mutation patterns between the mutated genes. IDH2 mutations relates with poor prognosis and possesses potential to be molecules for model of IR-AML prognostic stratification. Genetic testing based on HTS contributes to revealing the pathogenic mechanism of AML, and is significant for evaluating the prognosis of patients with AML.
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Humans , Middle Aged , High-Throughput Nucleotide Sequencing , Leukemia, Myeloid, Acute/genetics , Mutation , Prognosis , Retrospective StudiesABSTRACT
Aim To investigate the effect of cinobufagin on the migration and invasion of esophageal cancer Kyse-520 cells, and to explore the underlying molecular mechanism. Methods The rates of inhibition after treated with different concentrations of cinobufagin 12, 24, 48 h were detected by CCK-8 method, and the changes of cell migration and invasion were observed with wound healing and transwell assay. The mRNA expressions of FAK, Akt, PTEN, VEGF-A, MMP-2 and MMP-9 were detected by quantitative real-time polymerase chain reaction ( RT-qPCR ). The protein expressions of FAK, p-FAK ( Tyr397 ), Akt, p-Akt (Sei473 ), VEGF-A, PTEN, MMP-2 and MMP-9 were measured by Western blot. Results The results of CCK-8 showed that cinobufagin could inhibit the proliferation of Kyse-520 cells in a time- and concentration-dependent manner, and cinobufagin significantly inhibited the cell invasion and migration. Meanwhile, data from RT-qPCR and Western blot suggested that cinobufagin had no significant effect on mRNA and total protein of FAK and Akt, but it reduced the expression of p-FAK(Tyr397), p-Akt(Ser473), VEGF- A, MMP-2 and MMP-9, and increased the PTEN expression. Conclusions Cinobufagin significantly inhibits the invasion and migration of esophageal cancer Kyse-520 cells through inducing PTEN expression and down-regulating FAK/PI3K/AKT pathway.
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Mammalian target of rapamycin (mTOR) is an intracellular signaling pathway molecule which regulates various fundamental physiological processes. The mTOR signaling pathway plays an important role in synaptic plasticity, information transmission and processing, and neuroregulation. Dysregulation of the mTOR signaling pathway is generally considered to be related to the pathogenesis of autism spectrum disorder (ASD); meanwhile, the mTOR inhibitor can ameliorate the symptoms of ASD. The role of mTOR in the pathogenesis of ASD is summarized in this article to provide a theoretical basis for targeted therapy of ASD.
Subject(s)
Animals , Humans , Autism Spectrum Disorder , Signal Transduction , Sirolimus , TOR Serine-Threonine KinasesABSTRACT
OBJECTIVE@#To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients.@*METHODS@#The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed.@*RESULTS@#Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P<0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P<0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk.@*CONCLUSION@#MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Karyotype , Karyotyping , Mutation , Myelodysplastic Syndromes , Genetics , Prognosis , Retrospective Studies , Tumor Suppressor Protein p53 , GeneticsABSTRACT
Objective This retrospective study compared the detection rates of prostate cancer between freehand transperineal biopsy (FTPB) and template-guided transperineal biopsy (TYPB) in the patients with PSA levels < 20 ng/ml.Methods From April 2017 to April 2019,768 patients with PSA levels < 20 ng/ml were included into this study.Of these patients,406 underwent FTPB procedures and 362 underwent TTPB procedures.There were no significant differences of median age [66.00(61.00,70.00)vs.66.00 (61.00,71.25) years],height [170.00 (165.00,172.00) vs.170 (165.00,173.00) cm],weight [70.00 (63.88,75.00) vs.70.00 (63.75,75.00) kg],BMI [24.22 (22.22,25.95) vs.24.22 (22.49,25.82) kg/m2],PSA [8.75 (6.49,12.40) vs.8.69 (6.49,11.96) ng/ml],fPSA [1.18 (0.33,2.15) vs.1.15(0.76,1.88)ng/ml],prostate volume [39.79(25.55,53.94)vs.39.88(24.46,55.11)ml] between two groups.Patients' biopsy results were recorded,the differences of prostate cancer detection rates between these two groups were analyzed,specifically including the cancer with Gleason score ≥ 7 and the anterior zone cancer.Results The total prostate cancer detection rates were 33.7% (137/406) and 39.0% (141/362,P =0.134) in FTPB group and TTPB group respectively,and the detection rates of cancer with Gleason score≥7 were 23.9% (97/406) and 32.0% (116/362,P =0.012) respectively.The detection rates of anterior zone prostate cancer were 15.5% (63/406) and 27.3% (99/362,P <0.001).Moreover,in thepatients with PSA < 10 ng/ml,the prostate cancer detection rates were 29.8% (74/248) and 36.2% (81/224,P =0.144) respectively,while the detection rates of cancer with Gleason score ≥7 were 19.4% (48/248) and 29.9% (67/224,P =0.008) respectively.Conclusions There was no significant difference in the total prostate cancer detection rates between 12-core TTPB group and 20-core FTPB group in the patients with PSA < 20 ng/ml,but for the detection rate of cancer with Gleason score ≥ 7,TTPB group was significantly higher than FTPB group,especially in the patients with PSA < 10 ng/ml.In addition,for anterior zone prostate cancer,the detection rate of TrPB group was also higher than FTPB group.
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Objective To investigate the value of high density lipoprotein-cholesterol (HDL-C) in the diagnosis and risk assessment of non-alcoholic fatty liver disease (NAFLD).Methods A cross-sectional study and multistage stratified random sampling method were performed in epidemiological survey.According to inclusion and exclusion criteria,a total of 3 312 individuals were enrolled and divided into NAFLD group (913 cases) and non-NAFLD group (2 399 cases).The serum lipid levels were compared between the two groups.Receiver operating characteristic (ROC) curve was performed to evaluate the value of HDL-C in the diagnosis of NAFLD.The binary logistic regression models were established based on HDL-C level.The differences in liver function indexes were compared among the research objects with different HDL-C levels.T test and MannWhitney U test were performed for statistical analysis.Results The serum levels of total cholesterol,triglyceride and low density lipoprotein-cholesterol (LDL-C) of NAFLD group were all higher than those of non-NAFLD group ((5.24 ±0.92) mmol/L vs.(4.98 ±0.92) mmol/L,(1.95 ± 1.41) mmol/L vs.(1.13 ± 0.68) mmol/L,(3.31 ± 0.84) mmol/L vs.(3.09 ± 0.84) mmol/L),and the differences were statistically significant (t =-7.29,-22.38 and-6.84,all P < 0.01).However the serum HDL-C level of NAFLD group was lower than that of non-NAFLD group((1.30 ±0.33) mmol/L vs.(1.64 ±0.40) mmol/L),and the difference was statistically significant (t =24.93,P <0.01).The incidence of hypercholesterolemia,hypertriglyceridemia,hypo-high-density lipoprotein cholesterolemia and hyper-low-density lipoprotein cholesterolemia of NAFLD group was 48.0% (438/913),44.8% (409/913),31.0% (283/913) and 82.8% (756/913),respectively,which were significantly higher than that of non-NAFLD group (36.8%,882/2 399;13.2%,317/2 399;10.5%,251/2 399;71.8%,1 723/2 399),and the differences were statistically significant (x2 =34.65,385.43,206.18 and 42.37,all P < 0.01).Using the cut-off values of HDL-C ≤ 1.66 mmol/L in female and ≤ 1.33 mmol/L in male,the area under curve (AUC) values for NAFLD diagnosis were 0.720 (95% confidence interval (CI) 0.693 to 0.747) and 0.708 (95% CI 0.679 to 0.737),respectively,the sensitivity was 79.1% and 76.6%,and the specificity was 55.0% and 54.6%.The results of binary logistic regression models based on HDL-C level indicated that prevalence of NAFLD in female with low HDL-C was 4.584 times (95% CI 3.530 to 5.940,P <0.01) higher than that in female with high HDL-C;the prevalence of NAFLD in male with low HDL-C was 3.898 times (95% CI 3.020 to 5.030,P <0.01) higher than that of male with high HDL-C.The alanine aminotransferase (ALT),aspartate transaminase (AST),gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) levels of low HDL-C group were all higher than those of high HDL-C group (20.10 U/L,14.40 U/L to 29.40 U/L vs.16.80 U/L,12.70 U/L to 23.00U/L;19.20 U/L,16.00 U/Lto23.70 U/Lvs.19.00 U/L,16.00 U/Lto22.17 U/L;22.00 U/L,14.00 U/L to34.00 U/L vs.15.00 U/L,11.00 U/L to 23.00 U/L and 71.00 U/L,59.00 U/L to 85.00 U/L vs.66.00 U/L,55.00 U/L to 82.00 U/L),and the differences were statistically significant (Z =-10.53,-2.20,-14.19 and-5.87,all P<0.05).Conclusion The serum HDL-C level is negatively correlated with the risk of NAFLD level,and the NAFLD risk of individuals with low HDL-C level is significantly higher than individuals with high HDL-C level.
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Objective To perform an exploratory investigation on confocal laser endomicroscopy (CLE) in the diagnosis of malignant bladder tumour.Methods From June 10 to July 11,2017,6 male bladder cancer patients underwent white light cystoscopy (WLC) + CLE examination,aging 64-86 years (median 72 years).All patients received TURBT on suspected lesions.WLC and CLE imaging results were recorded and validated by pathologic specimens.Results Lesions confirmed by histopathology were 3 low grade non-invasive papillary urothelial carcinomas,1 high grade non-invasive papillary urothelial carcinoma,1 low grade invasive urothelial carcinoma,1 high grade invasive urothelial carcinoma,1 carcinoma in situ (CIS),1 high grade dysplasia,1 cystitis glandularis,1 chronic inflammation,and 1 scar tissue.For CLE images in the normal urothelium,three layers of cells with different presentation were observed,namely,the superficial umbrella cells,the intermediate cells smaller in size and uniformly shaped,and the capillary network in the lamina propria.For non-invasive urothelial carcinoma,tumour cells appeared as papillary lesions growing from fibrovascular cores,with low grade cells appearing monomorphic and more cohesively arranged,and high grade cells relatively pleomorphic,more disorganised and with tortuous blood vessels in the fibrovascular core.For invasive urothelial carcinoma,tumour cells invaded the lamina propria,with uniform appearances,poor cohesion and indistinct cellular borders,and high grade ones were more pleomorphic.CIS and inflammation both appeared as erythematous patch-like flat lesions under WLC and sometimes difficult to differentiate.Under CLE,the former appeared as dysplastic and disorganised cells with indistinct cellular borders,with intact lamina propria,and inflammatory cells were discovered as infiltrative clusters in the lamina propria that were uniformly shaped and loosely connected.Dysplasia appeared somewhat similar compared with CIS under WLC,but with lower cellular irregularity as confirmed with pathology.Cellular appearance and structure in scar tissue was similar to that in the normal urothelium,but superficial umbrella cells were more likely absent,with thinner cell layers,and inflammatory infiltration was sometimes discovered in the lamina propria.Conclusions CLE provides real-time cellular imaging of the urothelium,and shows promising potential for clinical diagnosis,especially in differentiating fiat urothelial lesions.Large prospective studies are required for further validation.
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We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital (Shanghai, China) from May 2007 to November 2015. TSV was successfully performed in 381 cases (90.9%). Hemospermia was alleviated or disappeared in 324 (85.0%) patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 (1.9%), 32 (7.6%), 341 (81.4%), and 38 (9.1%) cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.
Subject(s)
Adult , Humans , Male , Middle Aged , Ejaculatory Ducts/surgery , Endoscopy/methods , Hemospermia/surgery , Magnetic Resonance Imaging , Seminal Vesicles/surgery , Tomography, X-Ray Computed , Treatment Outcome , Urethra/surgeryABSTRACT
<p><b>OBJECTIVES</b>To evaluate the effectiveness and safety of Guipi Decoction (, GPD) as an adjunctive in the treatment of depression.</p><p><b>METHODS</b>A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1.</p><p><b>RESULTS</b>Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug signifificantly improved the symptoms of depression [weighted mean difference (WMD):-3.09; 95% confifidence interval (CI):-4.11 to-2.07] and increased the rates of effectiveness (OR: 4.75; 95% CI: 2.66-8.51) as well as recovery (OR: 1.73; 95% CI: 1.17-2.56). The adverse effects of GPD were not found to be signifificant in these studies.</p><p><b>CONCLUSIONS</b>The fifindings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any serious adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.</p>
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Objective To discuss the application of the systematic nursing management of "one specialty with four standardizations" in transrectal ultrasound guided prostate Biopsy. Methods We have set up the "one specialty with four standardizations" method and accomplished the systematic nursing management in the management of transrectal ultrasound guided prostate biopsy in Changhai Hospital from September 2014 to February 2015. One specialty means to set up the prostate biopsy full-time nurses and the four standardizations means the standardization of selecting criteria, appointment procedures, working process and the post-biopsy work.Results The whole procedure of prostate biopsy has been simplified and clarified. This management helped to shorten the time for making the appointment, reduce the incidences of postoperative complications significantly and increase the patients satisfaction. It helped to build a well-defined responsibility for all the medical staff in prostate biopsy and make sure the reasonable medical resource distribution and the efficiency of medical work. It also maximized the health rights of the patients and medical safety. During the period when the "one specialty with four standardizations" nursing management was in effect, no biopsy related adverse event, disputes or protests occurred. Both the patients and the relatives satisfaction degree have been raised significantly.Conclusions The "one specialty with four standardizations" nursing management in prostate biopsy helps to simplify the appointment procedure and this management turned out to be safe and effect. It has achieved preferable results in clinical application and worth further spreading.
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Objective To study the role of quality control circle(QCC) in reducing operation-related acute pressure ulcer.Methods The QCC activity group composed by 13 nursing staff analyzed the current situation and causality of operation-related acute pressure ulcer,and made the pointed counter measures to reducing the incidence rate.Results Following the development of QCC activity,the incidence rate of operation-related acute pressure ulcer decreased from 1.83% to 0.73%. The sense of responsibility,communication,teamwork,motivation,quality control ability and harmony of all the group members were improved significantly after the activity.Conclusions The QCC activity could not only effectively reduced the incidence rate of operation-related acute pressure ulcer,but also consolidated our team spirit and enhanced the quality management capability of all team members.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies.Current radiological examination is quite limited in diagnosing early HCC.Various treatments for HCC have definite indications,and there is still no effective treatment and prevention for recurrence and metastasis.Based on the recent development of molecular targeting nanotechnology for specific molecules in liver cancer cells,early diagnosis and the monitoring of recurrence and metastasis for HCC can be improved,and the specificity of drug in targeting cancer cells and the therapeutic effect on HCC can be significantly enhanced.The article reviewed the application and significance of molecular targeting nanotechnology in HCC diagnosis and treatment.
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Objective To investigate the potential roles of chromogranin A in pathogenesis of asthmatic inflammation,and to assess the regulation of montelukast on chromogranin A expression.Methods The rat asthma model was established with ovalbumin,and they were allocated to three groups,named asthma group,control group and montelukast group.The expressions of chromogranin A protein and mRNA at lung tissue were detected by immunohistochemisty or real-time PCR methods,and positive expression intensity of chromogranin A protein was assayed by optical density.The correlation between chromogranin A protein and mRNA was also analyzed.Results The expression levels of chromogranin A protein in asthma group(0.34 ±0.05 optical density)was significantly higher than that in control group (0.21 ±0.06 optical density)(P<0.01 ).The expression levels of chromogranin A mRNA in asthma group (4.02 ±0.95 relative quantity value)was significantly higher than that in control group(P<0.01 ).The expression levels of chromogranin A protein in montelukast group(0.28 ±0.04 optical density)was dramatically lower than that in asthma group (0.34 ±0.05 optical density)(P<0.05),while there were no statistical significance of chromogranin A mRNA(3.67 ±0.78 relative quantity value)between those two groups(P>0.05 ).But levels of mRNA was positively correlated with protein of chromogranin A (r=0.635,P<0.01).Conclusion Expressions of chromogranin A protein and mRNA at lung tissue were increased in asthmatic rats,and the results demonstrated that chromogranin A perhaps participated in the pathogenesis of asthma inflammation,but this function of chromogranin A protein could be down regulated by montelukast.
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<p><b>OBJECTIVE</b>To investigate the hematopoietic reconstitution in immunodeficiency NPG(TM) mice after transplantation of G-CSF-mobilized peripheral blood CD34(+) hemopoietic stem cells.</p><p><b>METHODS</b>CD34(+) cells were isolated from peripheral blood stem cells (PBSC) by magnetic activated cell sorting (MACS), and then were transplanted into NPG(TM) mice irradiated with sublethal dose of X ray by marrow cavity transplantation. The hemogram of mice after transplantation for 2, 4 weeks was observed; human cell populations (CD45(+), CD19(+)) in the peripheral blood of mice were dynamically analyzed by flow cytometry (FCM) at 4, 6, 8, 10 and 12 weeks after transplantation. Until the planned harvest at the 12 week after transplantation, the CD45(+), CD19(+) level in bone marrow, liver, spleen from each mouse were detected by flow cytometry; the expression of human Alu gene in the bone marrow cell of mouse was detected by PCR.</p><p><b>RESULTS</b>The purity of CD34(+) cells accounted for 96.3%; after irradiation, the nucleated cells and megalokaryocytes in the marrow cavity of NPG mice were reduced significantly or were lost, and reached the myeloablative effect. At week 4 after transplantation, components of blood cells in peripheral blood of transplanted mice were recovered to the level before irradiation; all the mice survived, human CD45(+), CD19(+) cells were found by FCM in the peripheral blood of all the surviving mice in transplantation group at week 4, 6, 8, 10, 12 after the transplantation; at the 12th week, the human Alu gene could be detected in the bone marrow of all the mice in transplantation group.</p><p><b>CONCLUSION</b>The human-mouse chimeric model is successfully established in irradiation-induced NPG mouse by transplantation of CD34(+) HSC from G-CSF-mobilized peripheral blood via marrow cavity.</p>
Subject(s)
Animals , Humans , Mice , Bone Marrow , Bone Marrow Cells , Bone Marrow Transplantation , Cord Blood Stem Cell Transplantation , Disease Models, Animal , Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cells , SpleenABSTRACT
<p><b>OBJECTIVE</b>This study was aimed to investigate the effect of mesenchymal stem cells (MSCs) on subsets and cytokine secretion of T lymphocytes.</p><p><b>METHODS</b>Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) were isolated by density gradient and were cultared by amplifying culture. The subsets and cytokine secretion of T lymphocytes were detected by flow cytomety after being co-cultured with UCBMSC.</p><p><b>RESULTS</b>The proliferation of lymphocytes was inhibited. CD4(+)T cell subsets were increased, CD8(+)T cell subsets decreased when co-cultured with UCBMSC; Th1 and Tc1 level significantly reduced, while Th2 and Tc2 level slightly increased.</p><p><b>CONCLUSION</b>The UCBMSC can inhibit the proliferation of lymphocytes, especially CD8(+)T cell subsets. In addition, UCBMSCs can reduce Th1 and Tc1 cells, and increase Th2 and Tc2 cells. UCBMSC may have the clinical application potential for preventing and remedying GVHD.</p>
Subject(s)
Humans , Coculture Techniques , Fetal Blood , Lymphocyte Count , Mesenchymal Stem Cells , Stem Cells , T-Lymphocyte SubsetsABSTRACT
<p><b>OBJECTIVE</b>To investigate the ability of UCB-derived MSCs to support the expansion of HSCs ex vivo and the possible mechanisms involved in this process.</p><p><b>METHODS</b>HSCs from UCB were co-cultured with UCB-derived MSCs for 14 days, and then the total number of HSCs and colony-forming units (CFU) were detected. Cytokines levels of MSCs supernatant were analyzed using ELISA.</p><p><b>RESULTS</b>The proliferation rate of HSCs co-cultured with MSCs was significantly higher than that of cultured HSCs alone (P<0.05). Furthermore, the addition of exogenous cytokines to the culture system significantly increased the proliferation rate of HSCs (P<0.05). MSCs had secretion of many cytokines, including GM-CSF, IL-7, IL-8, IL-11, SCF and SDF-1α.</p><p><b>CONCLUSION</b>UCB-derived MSCs as a feeder layer can be an alternative approach for ex vivo expansion of HSCs, and the cytokines by secreted UCB-MSCs may mediate the supportive role of MSC to HSC proliferation.</p>
Subject(s)
Humans , Antigens, CD34 , Cell Proliferation , Coculture Techniques , Cytokines , Fetal Blood , Mesenchymal Stem CellsABSTRACT
Ultrafine powder and cell wall-broken powder of herbal medicine lack of the morphological characters and microscopic identification features. This makes it hard to identify herb's authenticity with traditional methods. We tested ITS2 sequence as DNA barcode in identification of herbal medicine in ultrafine powder and cell wall-broken powder in this study. We extracted genomic DNAs of 93 samples of 31 representative herbal medicines (28 species), which include whole plant, roots and bulbs, stems, leaves, flowers, fruits and seeds. The ITS2 sequences were amplified and sequenced bidirectionally. The ITS2 sequences were identified using Basic Local Alignment Search Tool (BLAST) method in the GenBank database and DNA barcoding system to identify the herbal medicine. The genetic distance was analyzed using the Kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic tree was constructed using MEGA 6.0. The results showed that DNA can be extracted successfully from 93 samples and high quality ITS2 sequences can be amplified. All 31 herbal medicines can get correct identification via BLAST method. The ITS2 sequences of raw material medicines, ultrafine powder and cell wall-broken powder have same sequence in 26 herbal medicines, while the ITS2 sequences in other 5 herbal medicines exhibited variation. The maximum intraspecific genetic-distances of each species were all less than the minimum interspecific genetic distances. ITS2 sequences of each species are all converged to their standard DNA barcodes using NJ method. Therefore, using ITS2 barcode can accurately and effectively distinguish ultrafine powder and cell wall-broken powder of herbal medicine. It provides a new molecular method to identify ultrafine powder and cell wall-broken powder of herbal medicine in the quality control and market supervision.