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The p53 protein is an essential tumor suppressor in the human body that plays a critical role in preventing tumor formation by controlling cell cycle arrest and promoting apoptosis. Mutations in the p53 gene are frequently observed in more than 50% of tumor tissues and lead to the generation of mutant p53 proteins, which not only have a dominant-negative effect (DN) that hinders the function of wild-type p53 protein but also have gain-of-function (GOF) effects that stimulate tumor development by regulating cell metabolism, invasion, migration, and other processes. Therefore, mutant p53 protein has become a specific drug target for cancer therapy. However, the lack of a drug-binding pocket and smooth surface of mutant p53 proteins have made them undruggable targets for a long time. In recent years, with the development of high-throughput screening technology and an enhanced understanding of the structure and conformational changes exhibited by mutant p53 proteins, a multitude of small molecule compounds directed against mutant p53 protein have been identified, exhibiting substantial in vitro anti-tumor efficacy. Moreover, some of these compounds have entered clinical trials. This review summarized the direct and indirect strategies for the treatment of cancers targeting mutant p53, with a primary focus on the mechanisms of action of small molecule compounds that reactivate mutant p53 protein or degrade mutant p53 protein. The aim is to provide assistance for the development of innovative drugs targeting mutant p53 protein in the future.
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Objective:To discuss clinical effect of Zhuyu Zhixuetang to chronic endometritis (CE) with syndrome of Qi deficiency and blood stasis and to study improvement effect to pregnancy outcome. Method:One hundred and forty-four patients were randomly divided into two groups, patients in control group were 72 cases and in observation group were 72 cases. In control group, 66 patients completed the therapy because of 4 falling off or missing visit and 2 eliminated, and in observation group, 65 patients completed the therapy because of 3 falling off or missing visit and 5 eliminated. In two groups. anti-infection treatment was gicen to patients. Patients in control group got Fuke Qianjin Pian, 6 tablets/time, 3 times/day. Patients in observation group got Zhuyu Zhixuetang, 1 dose/day. The treatment was continued for 3 months and the follow up was recorded for 6 months. Before and after treatment, changes of menstrual volume, period and cycle were recorded. And hysteroscopy and color Doppler ultrasound of vagina were made, and endometrial morphology and endometrial receptivity were evaluated [endometrial thickness, resistance index (RI), pulsation index (PI) and blood flow index (FI)] were evaluated, and pathology of endometrial were tested. And scores of syndrome of Qi deficiency and blood stasis were graded, levels of interleukin-1 <italic>β</italic> (IL-1<italic> β</italic>), IL-6 and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) and T-lymphoid subsets (CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>) in peripheral blood were measured. Pregnancy and miscarriage were recorded and the safety was evaluated. Result:After treatment, menstrual volume, menstrual period, cycle and complete normal rate of menstruation in observation group were all higher than those in control group (<italic>P</italic><0.05). Endometrial thickness and FI were more than those in control group (<italic>P</italic><0.01), RI and PI were lower than RI and PI in control group (<italic>P</italic><0.01). And compared with control group, levels of IL-1<italic>β</italic>, IL-6, TNF-<italic>α</italic> and CD8<sup>+ </sup>were less (<italic>P</italic><0.01). And levels of CD3<sup>+</sup>, CD4<sup>+</sup> and CD4<sup>+</sup>/ CD8<sup>+</sup> were higher than the data in control group (<italic>P</italic><0.01). During 6 months follow-up, pregnancy rate in observation group was 46.97% (31/66) was higher than 27.69% (18/65) in control group (<italic>χ</italic><sup>2</sup>=5.197, <italic>P</italic><0.05). Total effective rate of endometrial morphology was 96.97% (64/66) higher than 86.15% (56/65) in control group (<italic>χ</italic><sup>2</sup>=4.981, <italic>P</italic><0.05). Total effective rate endometrial pathology was 95.45% (63/66) higher than 84.62% (55/65) in control group (<italic>χ</italic><sup>2</sup>=4.304, <italic>P</italic><0.05). Total effective rate of comprehensive clinical effect was 93.94% (62/66) higher than 81.54% (55/65) in control group (<italic>χ</italic><sup>2</sup>=4.696, <italic>P</italic><0.05). There was no adverse reactions related to traditional Chinese medicine. Conclusion:Zhuyu Zhixuetang can regulate menstruation, relieve clinical symptoms, improve endometrial morphology under hysteroscopy, regulate systemic and local immune inflammatory response, improve CP, thus improve pregnancy outcome, with better comprehensive effect and safety.
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This study investigated the protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori(Hp)-induced gastritis in mice and explored its possible mechanism. The chronic atrophic gastritis(CAG) model mice were randomly divided into four groups of model, total triterpenoids from C. speciosa(50 and 100 mg·kg~(-1)) and triple therapy, with C57 BL/6 J mice without Hp infection taken as the normal group. Mice in the treatment groups were given corresponding drugs once a day for 4 weeks. Then the following indexes were detected: the contents of reactive oxygen species(ROS), monocyte chemotactic protein 1(MCP-1), keratinocyte chemokines(KC), TNF-α, IL-1β, IL-6, IL-18, IL-4 and IL-10 in blood and gastric tissue, the activities and contents of LDH, MPO, SOD, GSH-Px, CAT and MDA in gastric tissue and the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood, gastric tissue and lysosome. Besides, the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), Bcl-2, Bcl-xl, Bax and Bad in gastric tissue were determined by quantitative real-time PCR. Western blot was employed to detect the protein expression levels of TLR4, MyD88, p-IKKβ, p-IκBα, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein(ASC), pro-caspase-1, caspase-1, thioredoxin-interacting protein(TXNIP), pro-IL-1β, pro-IL-18, Bcl-2, Bcl-xl, Bax, Bad, cytochrome C, apoptotic protease-activating factor-1(Apaf-1), pro-caspase-9, pro-caspase-3, cleaved-caspase-9, cleaved-caspase-3, poly(ADP-ribose) polymerase 1(PARP-1), cleaved-PARP-1 and cytosol and nucleus NF-κB p65 in gastric tissue. The results indicated that the total triterpenoids from C. speciosa significantly suppressed Hp proliferation, alleviated the damage to gastric mucosa and improved lymphocyte infiltration and gland atrophy. They were also effective in reducing the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood and gastric tissue, elevating the activities of β-glucuronidase and cathepsin D in lysosomal organelles, decreasing the contents of ROS, MCP-1, KC, TNF-α, IL-1β, IL-6, IL-18 in blood, MDA content and MPO and LDH activities in gastric tissue and increasing the contents of IL-4 and IL-10 in blood and activities of SOD, CAT and GSH-Px in gastric tissue. Other phenomena were also observed after the treatment with total triterpenoids from C. speciosa, including the down-regulation of the mRNA and protein expression levels of TLR4, MyD88, Bax and Bad, the protein expression levels of p-IKKβ, p-IκBα, NLRP3, ASC, pro-caspase-1, caspase-1, TXNIP, pro-IL-1β, pro-IL-18, cytochrome C, Apaf-1, cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 and nuclear NF-κB p65, reduction of p-IKKβ/IKKβ and p-IκBα/IκBα ratios and up-regulation of the mRNA and protein expression levels of Bcl-2 and Bcl-xl, up-regulation of pro-caspase-9, pro-caspace-3, cytosol NF-κB p65 protein expression levels and Bcl-2/Bax and Bcl-xl/Bad ratios in gastric tissue. These aforementioned results suggest that the total triterpenoids from C. speciosa have significant protective effects against CAG induced by Hp, and its mechanism may be related to enhancing the function of endogenous antioxidant system, suppressing the oxidative stress and inflammatory reaction induced by Hp, correcting lysosomal dysfunction and inflammatory activation of TLR4/NF-κB/NLRP3 inflammasome signaling pathway and thus inhibiting mitochondria-mediated apoptosis.
Subject(s)
Animals , Mice , Gastritis/drug therapy , Helicobacter pylori , NF-kappa B/genetics , Rosaceae , TriterpenesABSTRACT
OBJECTIVE@#To explore the feasibility and clinical effects of arthroscopic treatment for the calcific tendinitis at soft tissues around hip.@*METHODS@#A total of 16 patients diagnosed as the calcific tendinitis at soft tissues around hip from May 2013 to July 2018 were retrospectively analyzed. All the 16 patients received arthroscopic procedures. There were 10 males and 6 females with an average age of 35 to 63 (44.50±6.67) years old and 9 left hips, 6 right hips were involved. The course of disease were 1 to 8(3.18±1.97) days. Clinical effects were evaluated with visual analogue scale(VAS), modified Harris hip scores (HHS), nonarthritic hip score (NAHS) and imaging examinations before operation, 1 day after operation and the final follow-up.@*RESULTS@#All 16 patients successfully finished the arthroscopic procedures in 0.5 to 1.2 (0.75±0.21) hours. Primary healing of incision were obtained without any complications of infection, wound hematocele and neurovascular injury. All 16 patients received an average postoperative follow-up of 6 to 12 (9.6±2.3) months. Before operation, the VAS were 7.88±0.72, modified HHS were 29.25±3.23, NAHS were 27.42±3.08. The 1st day postoperative VAS were 2.19±0.66, modified HHS were 82.56± 5.64, NAHS were 82.11±2.94, all the difference were statistically significant between before and 1 day after operation (@*CONCLUSION@#Arthroscopic treatment for the calcific tendinitis at soft tissues around hip is effective.It has advantages of minimal invasive, rapid pain relief, rapid hip joint function recovery and definite clinical effects.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Arthroscopy , Follow-Up Studies , Hip/surgery , Hip Joint/surgery , Retrospective Studies , Tendinopathy/surgery , Treatment OutcomeABSTRACT
@#Objective:To observe the interactive effects of early exercise and γ-aminobutyric acid (GABA) receptor antagonists on the neurologic function and brain-derived neurotrophic factor (BDNF) expression in the cerebral ischemia-reperfusion (I/R) rat model. Methods:Male Sprague-Dawley rats were divided into sham (<italic>n</italic> = 10), I/R (<italic>n</italic> = 10), exercise (EX) (<italic>n</italic> = 10), pentetrazol (PTZ) (<italic>n</italic> = 10) and pentetrazol plus exercise (PTZEX) (<italic>n</italic> = 10) groups. All the rats, except the sham group, accepted middle cerebral artery occlusion (MCAO) for one hour and reperfused. Since two days after reperfusion, PTZ and PTZEX groups accepted PTZ, a GABA receptor antagonist, 0.25 mg/kg peritoneal injection, once a day for five days; while EX and PTZEX groups ran on a treadmill, 30 minutes a day for five days. Seven days after reperfusion, all the rats were assessed with neurobehavioral score, the infarct volumes were assessed with TTC, and BDNF expression in ischemic penumbra was detected with reverse transcription polymerase chain reaction and ELISA. Results:Compared with I/R group, the neurobehavioral scores of EX group, PTZ group and PTZEX group improved, the volumes of cerebral infarction reduced (<italic>P </italic>< 0.05), and PTZEX group was the best (<italic>P </italic>< 0.05). The expression of BNDF was the most in PTZEX group (<italic>P </italic>< 0.05). Conclusion:Early exerxise combined with PTZ could promote the recovery of neurologic function in I/R rats, which may be related to the up-regulation of BDNF.
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Objective: To rapidly analyze the chemical constituents of Huoxue Zhitong Capsules performed by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Methods: A Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) was used with 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile as a mobile phase. The flow rate was 0.4 mL/min; The samples were collected in positive and negative ion modes, respectively. The processed data was analyzed by Masslynx 4.1TM software. Results: A total of 113 compounds were identified in positive and negative ion mode, including terpenoids, saponins, organic acids, benzoquinones and others, and the medicinal sources of the compounds were assigned. Conclusion: The established method can systematically, quickly and accurately identify various chemical components of Huoxue Zhitong Capsule. This study provides a reference for the selection of quality evaluation indicators and the basis of pharmacodynamics of Huoxue Zhitong Capsule.
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To observe the effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1/NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by dextran sulfate sodium (DSS) in mice, C57BL/6 mice were randomly divided into normal group, model group, total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) groups and sulfasalazine (250 mg·kg⁻¹) group. The ulcerative colitis (UC) model was induced by orally administering 2.5% DSS to the experimental mice, and the corresponding drugs were given to each group 3 days before the administration with 2.5% DSS. The normal group and the model group were given the equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage continuously for 10 days, q.d. The general conditions of the mice were observed on a daily basis, and the disease activity index (DAI) score was recorded. On the 10th day after the treatment, mice were put to death, the contents of TNF-α, IL-1β, IL-6, IFN-γ, IL-4 and IL-10 in the blood were detected, colon length was measured, colon mucosa damage index (CMDI) score was calculated, and MPO activity detection and histomorphology analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of E-cadherin, occluding,MUC2 and TFF3; the protein expressions of SIRT1, IKKβ, p-IKKβ, IκBα, p-IκBα and cytosol and nucleus PPARγ, NF-κBp65 in intestinal tissue were detected by western blot. The results indicated that total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) could significantly improve the general conditions of UC mice, reduce the DAI, CMDI and histopathological scores, increase the colon length, reduce the colonic mucosa ulcers, erosion and inflammatory infiltration, restore the normal intestinal mucosal barrier function, reduce the contents of TNF-α, IL-1β, IL-6, IFN-γ, increase the contents of IL-4 and IL-10 in the blood, inhibit MPO activity in colon tissue, up-regulate the mRNA expressions of E-cadherin, occludin, MUC2 and TFF3 in colon tissue, down-regulate the protein expressions of cytosol PPARγ, tissue p-IKKβ, p-IκBα and nucleus NF-κBp65 in the colon tissue, decrease the p-IKKβ/IKKβ and p-IκBα/IκBα ratios, up-regulate the protein expressions of nucleus PPARγ, tissue SIRT1 and cytosol NF-κBp65 (<0.05 or <0.01, respectively), with a dose-effect relationship between the total triterpenoids of C. speciosa treated groups. These findings suggested that total triterpenoids of C. speciosa had a significantly therapeutic effect on UC mice induced by DSS, its mechanism might be related to the regulation of PPARγ/SIRT1/NF-κBp65 signaling pathway, the inhibition of pro-inflammatory factor formation and the up-regulation of protein expression of protective factors.
Subject(s)
Animals , Mice , Colitis, Ulcerative , Drug Therapy , Colon , Dextran Sulfate , Disease Models, Animal , Intestinal Mucosa , Mice, Inbred C57BL , PPAR gamma , Metabolism , Random Allocation , Rosaceae , Chemistry , Signal Transduction , Sirtuin 1 , Metabolism , Transcription Factor RelA , MetabolismABSTRACT
Tumor suppressor p53 protein can regulate the tran-scription of target genes, to control cell apoptosis, aging and other life activities,but mutant p53 is prone to losing antitumor function, thus promoting tumor development. At present, p53 protein has become one of the hot targets for the treatment of cancer. This article mainly introduces the structure and mechanism of small molecular compounds with restoring activity of mutant p53 as the target.
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<p><b>OBJECTIVE</b>To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.</p><p><b>METHODS</b>The immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.</p><p><b>RESULTS</b>There was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.</p>
Subject(s)
Humans , Antigens, CD , Metabolism , Cell Count , Flow Cytometry , Granulocyte Precursor Cells , Classification , HLA-DR Antigens , Metabolism , Immunophenotyping , Leukemia, Promyelocytic, Acute , Classification , Allergy and Immunology , Leukocyte Common Antigens , Metabolism , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship of leptin gene polymorphism with obesity in ethnic minority Hui and Uygur children in China.</p><p><b>METHODS</b>Sixty-eight ethnic minority (35 Hui and 33 Uygur) children with obesity and 69 age-matched minority (36 Hui and 33 Uygur) children without obesity were recruited from six primary schools in the sub-urban areas of Urumqi. Venous blood was sampled from all subjects after fasting for 12 hours. Leptin gene C2549A polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. Blood concentrations of lipids, leptin and insulin were measured with biochemical methods and radioimmunoassys, respectively.</p><p><b>RESULTS</b>In the 137 children tested, the prevalence of AA, AC and CC genotype was 9.5%, 33.6% and 56.9%, respectively. A allele frequency was significantly different between the two ethnic (i.e. Hui and Uygur) groups (P<0.05). A allele frequency and AA+ AC genotype frequency were not significantly different between obese and non-obese children in both ethnic groups (P>0.05). Blood leptin levels were not significantly different between obese and non-obese children with an AA+AC or CC genotype in both ethnic groups (P>0.05).</p><p><b>CONCLUSIONS</b>Leptin gene polymorphisms exist in Hui and Uygur children. The C2549A polymorphism is not significantly associated with the prevalence of obesity in both Hui and Uygur children.</p>
Subject(s)
Child , Female , Humans , Male , China , Ethnology , Genotype , Leptin , Blood , Genetics , Lipids , Blood , Obesity , Blood , Genetics , Polymorphism, GeneticABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of benzene poisoning on the expression of multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) in the bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice.</p><p><b>METHODS</b>C57BL/6 mice were randomly divided into control group (n = 24), low-dose group (n = 24), medium-dose group (n = 24), and high-dose group (n = 24) to receive corn oil, 25 mg/kg benzene, 50 mg/kg benzene, or 100 mg/kg benzene by gavage, once daily, 5 days/weeks, for 4 weeks. The mice were sacrificed on day 12, 26, or 29 of poisoning. Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs.</p><p><b>RESULTS</b>On day 12, the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). On day 26, the white blood cell count in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). At each time point, the mRNA expression of MDR1 gene in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.01). On day 26, the P-gp expression in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group, and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group (P < 0.01 or P < 0.05). On day 29, the P-gp expression in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Benzene poisoning can affect the expression of MDR1 gene and P-gp, which may be one of the mechanisms of benzene hematotoxicity.</p>
Subject(s)
Animals , Male , Mice , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Metabolism , Benzene , Toxicity , Bone Marrow Cells , Cell Biology , Metabolism , Drug Resistance, Multiple , Genetics , Mice, Inbred C57BL , Monocytes , Cell Biology , MetabolismABSTRACT
Objective To investigate the association between C2549A polymorphism of leptin gene and the Trp64Arg polymorphism of the β3-adrenergic receptor gene(β3-AR gene) and obesity in Kazak school-age children.Methods Totally 92 obese children and 71 healthy controls were selected from 6 to 12 years old in Kazak school-age children from the area around Urumqi.Genotype of the C2549A polymorphism of leptin gene and the Trp64Arg polymor phism of β3-AR gene were determined by polymerase chain reaction and restriction fragment length polymorphism methods.Results 1.The difference in distribution of the β3-AR gene Trp64Arg genotype of obesity and healthy controls of Kazak children was statistically significant (x2 =10.472,P < 0.05),but the difference in distribution of the alleles was not statistically significant (x2 =3.541,P > 0.05).2.The differences in distribution of the leptin C2549A genotype and alleles of the 2 groups were all statistically significant,and the odds ratio of the alleles(0.608) and 95% CI 0.380-0.972 suggested that the mutation occurrence of obesity might have certain protective effect.3.The difference in distribution of the genotype of β3-AR gene Trp64Arg polymorphism and leptin gene promoter area C2549A polymorphism in the same individual joint action of 2 groups was statistically significant (x2 =15.978,P < 0.05),but the difference in distribution of the alleles in the same individual joint action of 2 groups was not statistically significant (x2 =6.362,P > 0.05).Conclusions 1.There were distributions of the Trp64Arg polymorphism of β3-AR gene and the C2549A polymorphism of leptin gene in Kazak school-aged children in Xinjiang.2.These results suggested that C2549A mutation of leptin gene might have certain protective effect in Kazak children obesity,and the Trp64Arg polymorphism of β3-AR gene might be associated with Kazak children obesity.3.These results suggested that the Trp64Arg polymorphism of β3-AR gene and the C2549A polymorphism of leptin gene in the same individual joint action might be associated with Kazak children obesity in Xinjiang.
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This study was purposed to analyse the immunophenotypic characteristics of chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS) and acute monocytic leukemia (AML-M5b) by using multiparameter flow cytometry, and to explore its significance in diagnosis and differential diagnosis. The immunophenotypic characteristics of bone marrow samples from 14 CMML patients, 48 MDS patients, 46 AML-M5b patients and 18 normal persons were analyzed and compared by multiparametric flow cytometry. The results showed that the ratio of monocytes in CMML patients was obviously higher than that in MDS, AML-M5b patients and normal persons (P < 0.05), but there was no statistically significant difference between bone marrow samples of MDS and AML-M5b patients as well as normal persons. The ratio of blast cells in MDS patients was obviously higher than that in normal persons (P < 0.05), but did not show significant difference as compared with CMML patients. The ratio of mature granulocytes in AML-M5b patients was obviously lower than that in CMML and MDS patients as well as normal person bone marrow (P < 0.05). Certain differences of CD45/SSC characteristics in MDS, AML-M5b and CMML patients were found in comparison with normal persons. The abnormal expression of CD2, CD56, and CD14 tailing phenomenon were observed in CMML patients in comparison with bone marrow samples of MDS, AML-M5b and normal persons (P < 0.05). Lack and decrease of CD15 expression in MDS and CMML patients was significant different from AML-M5b and normal persons marrow, abnormal expression rate of CD15 in CMML patients was higher than that in MDS patients (P < 0.05), the CD13/CD11b/CD16 abnormal expression of granulocytes was seen in both CMML and MDS patients, but there was no statistically significant difference between them. Other antigens showed abnormality of varying degrees, but did not have any statistical significance. It is concluded that MDS, CMML and AML-M5b displayed a certain degree of similarity, and also possess their own immunophenotype characteristics. Comprehensive analysis of immunophenotype by multiparameter flow cytometry may be important for differential diagnosis among CMML, MDS and AML-M5b. High percentage of monocytes, abnormal coexpression of CD2, CD56 and CD14 tailing phenomenon, lack or decrease of CD15 as well as abnormal expression of CD13/CD11b/CD16 in granulocytes may play important roles in diagnosis of CMML.
Subject(s)
Humans , Case-Control Studies , Flow Cytometry , Methods , Immunophenotyping , Methods , Leukemia, Monocytic, Acute , Diagnosis , Allergy and Immunology , Leukemia, Myelomonocytic, Chronic , Diagnosis , Allergy and Immunology , Myelodysplastic Syndromes , Diagnosis , Allergy and ImmunologyABSTRACT
This study was purposed to investigate the immunophenotypic characteristics in multiple myeloma (MM) cells and their significance. Thirty three cases of MM and 12 cases of reactive plasmacytosis (as control group) were enrolled in the study. The expressions of surface antigens in MM cells were detected with flow cytometry by using direct immunofluorescent technique and gating method of CD38/SSC and were confirmed with morphologic observation of myeloma cells. The results indicated that the proportion of myeloma cells detected by morphologic examination was 6.0% - 76.0%. With CD38/SSC gating method, a cluster of CD38 bright positive cells could be detected in their scatter plot, the proportion ranged from 0.99% to 57.54%. Most phenotype of MM was 38(st+)CD138(+)CD19(-)CD56(+) (78.8%). While the expressions of CD20, CD33, CD117, HLA-DR were seen in some MM patients, the positive rates were 12.1%, 15.2%, 30.3%, 9.1%, respectively; the expression of other antigens was negative. cκ or cλ monoclonal restriction was detected in 27 cases (81.8%) of MM, both cκ and cλ in the remaining cases of MM was negative. It is concluded that detecting the immunophenotype of MM patients by flow cytometry with CD38/SSC gating method and basing on the heterogeneity of cell antigens can discriminate myeloma cells from normal plasma cells, which provides evidence for targeted therapy and prognosis evaluation.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Flow Cytometry , Methods , Immunophenotyping , Multiple Myeloma , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To study the sleep quality and quantity and their influencing factors in Uigur and Hui children in Xinjiang Province.</p><p><b>METHODS</b>From March to December of 2007, 912 Uigur and 1019 Hui school children (6 to 14 years) were randomly sampled from 6 cities of Xinjing Province. The questionnaire on children's sleep states and sleep environments was filled in by children's parents.</p><p><b>RESULTS</b>The mean sleep time of Uigur and Hui children was 10.1±1.4 hrs. The sleep time in Uigur children was significantly less than that in Hui children (9.7±1.2 hrs vs 10.4±1.5 hrs; P<0.05). The mean incidence of sleep disorders was 23.56%. The Uigur children had a lower incidence of sleep disorders compared with the Hui children (18.42% vs 28.16%; P<0.001). Ethnic group, sleep latency, use of a swing bed, family history of snore, watching TV before sleeping, hypertrophy of tonsils, eating before sleeping, feeding patterns and recurrent upper respiratory tract infection were the factors associated with the sleep quality and quantity.</p><p><b>CONCLUSIONS</b>The influencing factors of sleep quality and quantity are multifactorial in Uigur and Hui children in Xinjiang Province. Pediatrician, child health care doctors and parents should pay more attention to children's sleep. The incidence of sleep disorders is different between Uigur and Hui children, suggesting that more research for the prevention and treatment of sleep disorders should be performed in different ethic groups.</p>
Subject(s)
Adolescent , Child , Female , Humans , Male , China , Epidemiology , Ethnology , Logistic Models , Risk Factors , Sleep , Physiology , Sleep Wake Disorders , Epidemiology , Ethnology , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To study the effects of TrkB-BDNF signal pathway on the synthesis and secretion of vascular endothelial growth factor (VEGF) in human neuroblastoma cells (NB).</p><p><b>METHODS</b>TrkB protein expression in SY5Y cells before and after all-trans-retinoicacid (ATRA) treatment was detected by Western blot. P-TrkB protein expression in SY5Y cells before and after the treatment of ATRA along with BDNF was also detected by Western blot. VEGF concentrations in the SY5Y cell culture supernatants were measured using ELISA after the treatment with ATRA, BDNF, tyrosine kinase inhibitor K252a and PI3k inhibitor LY294002.</p><p><b>RESULTS</b>TrkB protein was undetectable in SY5Y cells before ATRA treatment. After the treatment of 1, 10 and 100 nM/L ATRA for five days, TrkB protein was expressed in SY5Y cells and the TrkB protein level increased with the increasing ATRA concentration. P-TrkB protein was not expressed in SY5Y cells treated only with 10 nM/L ATRA, but it was detectable after the treatment of ATRA along with BDNF. VEGF concentrations in the group treated with ATRA+BDNF were significantly higher than those in the untreated control and the ATRA alone treatment groups (P<0.01). VEGF concentrations in the K252a pretreated ATRA+BDNF group were significantly lower than those in the group treated with ATRA+BDNF (P<0.05). VEGF concentrations in the LY294002 treatment group (ATRA+LY294002+BDNF group) were also significantly lower than those in the group treated with ATRA+BDNF (P<0.01).</p><p><b>CONCLUSIONS</b>Activation of TrkB-BDNF signal pathway may increase the synthesis and secretion of VEGF in human NB cells. The synthesis and secretion of VEGF can be inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway PI3K/Akt with LY294002.</p>
Subject(s)
Humans , Brain-Derived Neurotrophic Factor , Physiology , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Neuroblastoma , Metabolism , Pathology , Phosphatidylinositol 3-Kinases , Physiology , Proto-Oncogene Proteins c-akt , Physiology , Receptor, trkB , Physiology , Signal Transduction , Physiology , Tretinoin , Pharmacology , Vascular Endothelial Growth Factor AABSTRACT
In order to investigate the expression and the relationship of ubiquitin associated protein 1 (ubap1) gene and tumor-suppressor gene p16 in acute leukemia, 68 cases of acute leukemia and 22 control cases were selected in this experiment, FQ-PCR technique was used to detect the mRNA expression level of ubap1 gene and p16 gene in their bone marrow cells. The results showed that as compared with the control group, the ubap1 gene in acute leukemia group highly expressed (p<0.01), while the p16 gene lowly expressed (p<0.01). But grouping of patients according to FAB revealed that as compared with the control group, the ubap1 gene expression displayed statistical difference only in M4 and M5 of adult AML (p<0.05), while the p16 gene expression in all groups of adult AML showed significant difference (p<0.05) except M1 and M2. In addition to this, the ubap1 gene and p16 gene mRNA expression in AL was not relate with chromosome abnormality (p>0.05). A negative correlation (r=-0.827, p<0.01) was found between the ubap1 gene and p16 gene mRNA expressions in the control group. It is concluded that the upregulation of ubap1 gene expression mainly and the downregulation of p16 gene expression mainly may simultaneously participate in the pathogenesis of acute leukemia. High expression of ubap1 gene influences the M4 and M5 subtypes in AML. This discovery provides important theoretical basis for the further investigation of pathogenesis and targeting therapy of AL.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Bone Marrow Cells , Metabolism , Carrier Proteins , Genetics , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p16 , Genetics , Gene Expression , Leukemia , Genetics , Metabolism , Pathology , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to investigate whether the induction of caspase-8 by γ-interferon (IFNγ) renders neuroblastoma (NB) cells sensitive to tumor necrosis factor related apoptosis inducing ligand(TRAIL).</p><p><b>METHODS</b>Caspase-8 mRNA expression was determined by RT-PCR. The effects of IFNγ, TRAIL, IFNγ +TRAIL and caspase-8 inhibitor+ TRAIL on the growth and apoptosis of NB cells were detected with the methods of reduction rate of Alamar Blue assay and flow cytometry. The relative caspase-8 activity was measured with colorimetric assay.</p><p><b>RESULTS</b>Caspase-8 expression was detectable in CHP212 cells which were sensitive to TRAIL, with an increased expression after treatment with IFNγ. Caspase-8 was undetectable in SH-SY5Y(SY5Y) cells which were resistant to TRAIL, but an increased expression of caspase-8 mRNA was found after treatment with IFNγ. Moreover, TRAIL combined with IFNγ induced apoptosis in SY5Y cells. The relative caspase-8 activity of CHP212 cells increased with the prolonged TRAIL action time. The relative caspase-8 activity of SY5Y cells in the IFNγ+TRAIL group was significantly higher than those of the control, IFNγ, TRAIL and inhibitor groups.</p><p><b>CONCLUSIONS</b>NB cells expressing caspase-8 are sensitive to TRAIL. TRAIL induces apoptosis in NB cells with an increase of relative caspase-8 activity.</p>
Subject(s)
Humans , Apoptosis , Caspase 8 , Physiology , Cell Line, Tumor , Flow Cytometry , Interferon-gamma , Pharmacology , Neuroblastoma , Drug Therapy , Pathology , Reverse Transcriptase Polymerase Chain Reaction , TNF-Related Apoptosis-Inducing Ligand , PharmacologyABSTRACT
This study was aimed to quantitatively detect the levels of beta-catenin and cyclin D1 mRNA in various subgroups of acute myeloid leukemia (AML) and to analyze their potential relationship, so as to provide theoretical basis for exploring the role of Wnt/beta-catenin pathway in the pathogenesis of AML. Real time fluorescent quantitative RT-PCR was used to detect the relative expression levels of beta-catenin and cyclin D1 mRNA, to analyze changes of the two gene expressions and their relationship. The results showed that the beta-catenin mRNA expression level in BMMNC of AML patients was significantly higher than that in benign blood disease patients (p < 0.05), but no statistical difference was found among the various subgroups of AML (p > 0.05). In AML there was overexpression of cyclin D1 mRNA, and its expression level was significantly higher than that in benign blood disease group (p < 0.05), but there was no statistical difference among the subtypes of AML. The expression levels of beta-catenin and cyclin D1 were correlated each other in AML-M(1), M(2) and M(4) (r values were 0.822, 0.627, 0.712 respectively; p values were 0.001, 0.020, 0.002 respectively). It is concluded that the over-expressions of beta-catenin and cyclin D1 exit in AML patients, and the significant correlation appears in part of the subgroups, which means that the Wnt/beta-catenin pathway is aberrantly activated in AML, probably activating the downstream target gene cyclin D1 and participating in the regulation of cell cycle disturbance and abnormal proliferation of leukemic cells.
Subject(s)
Adult , Female , Humans , Male , Young Adult , Cyclin D1 , Metabolism , Leukemia, Myeloid, Acute , Genetics , Metabolism , RNA, Messenger , Metabolism , Signal Transduction , beta Catenin , Genetics , MetabolismABSTRACT
Wnt/beta-catenin is the most important and more understanding pathway in Wnt pathways, which is closely related to pathogenesis and development of many solid tumors. Recently, researches discovered that Wnt/beta-catenin signal pathway may be involved in malignant hematopoiesis, and abnormally activated in many hematological-malignancies. This article reviews the newest studies on relationship between Wnt/beta-catenin signal pathway and hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, acute leukemia and so on) in order to reveal the related pathogenesis of hematological malignancies and provide new opinions for target therapy of these diseases.