Objective The purpose of the present study was to understand the genotoxicity of aristolochic acid(AA).Methods The mouse lymphoma assay(MLA)was employed to detect the genotoxicity of AA.The cells(L5178Y TK)were treated with AA by adding it into the culture medium at the concentrations of 15,30,60and 120 ?g/ml and then the mutant frequency(MF)was calculated.Results At the dose of 30,60 and 120 ?g/ml,MF increased significantly compared with the control(P

Intrauterine growth retardation (IUGR) is one of the most commonly encountered developmental toxicity, which could lead to perinatal morbidity and mortality, be also extended from the fetus to adulthood, and seriously affect the quality of the population. Caffeine widely exists in a variety of daily beverages and some drugs. Its consumption is increasing year by year. Caffeine intake during pregnancy is one of the risk factors for IUGR. However, its mechanism of adverse outcome based on embryonic research is still unclear. In this paper, the possible mechanisms of caffeine-induced IUGR focusing on 3 important factors-the mother, placenta and fetus were explored. Caffeine's impact on the mother is the chronic activation of renin-angiotensin system; on the placenta, caffeine induces cell damage or the failure of the cell proliferation/apoptosis balance, leading to blockage of blood supply to the placenta; caffeine is also capable of directly affecting fetal development through interfering its neuroendocrine.

Objective To investigate the effects of sex hormone-binding globulin (SHBG)gene in the apoptosis of human trophoblastic cells.Methods The siRNA specific-targeting SHBG gene was transfected into human trophoblastic cells and they were divided into six groups:trophoblasts without transfection in normal control groups(group Ⅰ);transfect liposome in blank control groups(group Ⅱ);transfect nonspecific siRNA in negative control groups(group Ⅲ);transfect SHBG siRNA-Ⅰ,SHBG siRNA-Ⅱ,SHBG siRNA-Ⅲ respectively in trans-fection group(group Ⅳ,Ⅴ,Ⅵ).Hoechst 33258 dying method was used to detect cell apoptosis.SHBG and Caspase-3 mRNA profiling and the level of SHBG and caspase-3 protein were detected by real-time PCR and Western blot.Results There was no statistical significant difference in the gene expression and protein level of SHBG and caspase-3 in group Ⅰ,Ⅱ and Ⅲ (P >0.05).In Ⅳ,Ⅴ and Ⅵ group,there was no statistical significant difference in the expression level of SHBG and caspase 3 (P >0.05).Compared with group Ⅰ,Ⅱ and Ⅲ,the a-mount of SHBG gene expression decreased obviously,the caspase-3 mRNA and protein level increased obviously and the trophoblast cell ap-optosis increased markedly (P <0.05).Conclusion Through siRNA interference technology can reduce SHBG gene expression in human trophoblastic cells,and it can lead to excessive apoptosis of human trophoblasts cells.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and a risk of transformation into acute leukemia. Approximately 30% of patients with MDS will progress and develop into acute myeloid leukemia (AML), especially in the patients with high-risk MDS, which can be named as secondary acute myeloid leukemia (sAML or MDS/AML). Generally, chemotherapy for sAML hardly has any efficacy. The only way to cure the patients with sAML is allogeneic hematopoietic stem cell transplantation, but unfortunately, only few patients are appropriate for transplantation. So it is important to study the mechanisms of progression of MDS to AML and to explore the potent drug for clinical use. This review summarizes the mechanism of MDS transformation into AML from chromosomal abnormality, aberrant DNA methylation and gene mutation, such as AML1/RUNX1 mutations, FLT3 mutations and PI-PLCβ1 mono-allelic deletion.
Chromosome Aberrations ; DNA Methylation ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Myelodysplastic Syndromes ; genetics ; pathology

Deferasirox is a new oral iron chelator. It is the first oral iron chelator approved in USA by FDA for transfusion-dependent patients above 2 years suffering from severe chronic iron overload. It is also recommended as the initial therapy for patients over the age of 6 years who are suffering from beta-thalassaemia. The clinical study is developing in China. This review focuses the related studies and the latest progression about deferasirox. The phase II and III clinical trials and pharmacokinetics indicated that deferasirox is a safety and effective oral iron chelator, can significantly decrease the myocardial and hepatic iron load, also is easy to accept for patients. The common adverse reactions are gastrointestinal symptom and rash. But it was recently reported that deferasirox has some rare adverse events to which we must attach importance, especially for the special people. Besides the patients with chronic iron overload resulting from blood transfusions (transfusional hemosiderosis), the drug is also used for the patients who has accepted auto-SCT or suffered from reversible renal inadequacy caused by Fanconi syndrome. The standard dosage is not useful to every patient. The clinician should adjust dosage based on the patient's condition and related indexes. The serum ferritin is not one and reliable index to monitoring the effect and adjust the dosage. Otherwise, this review recommends some new characters of deferasirox, e.g. anti-fungus, anti-cell proliferation and so on.
Benzoates ; administration & dosage ; Clinical Trials as Topic ; Humans ; Iron Chelating Agents ; administration & dosage ; Triazoles ; administration & dosage

OBJECTIVETo study the anticancer activity of the Clematis manshrica saponins in vivo.

METHODAnticancer activities were tested in mice with experimental tumor (S180, HepA and P388) in vivo.

RESULTThe Clematis manshrica saponins showed a significant anticancer activities on Sarcoma-180, HepA and P388 implanted in mice. In S180 sarcoma, the average tumor inhibition rates were 42.78%, 52.06% and 58.25% (P < 0.05-0.01) respectively; The mean inhibition rates were 37.44%, 52.05% and 59.36% (P < 0.05-0.001) in Hep A tumor separately; while in P388 tumor, the mean inhibition rates were 34.50%, 46.78% and 54.39% (P < 0.05-0.01), respectively.

CONCLUSIONThe results indicate that Clematis manshrica has obvious antitumor effects against various transplanted tumor in mice.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Clematis ; chemistry ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Leukemia P388 ; pathology ; Liver Neoplasms ; pathology ; Male ; Mice ; Neoplasm Transplantation ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Saponins ; administration & dosage ; isolation & purification ; pharmacology ; Sarcoma 180 ; pathology

The study was aimed to investigate the effective therapeutic method for patients with multiple myeloma accompanied with amyloidosis. A 58-year-old patient diagnosed as multiple myeloma accompanied with amyloidosis in four limbs was enrolled in this study. The various clinical and laboratorial examinations were performed, including bone marrow smear, immunologic test, radiography and so on. Patient received chemotherapeutic drugs and then autologous hematopoietic stem cell transplantation (auto-HSCT). The result showed that hematopoietic reconstitution was achieved at 23 days after auto-HSCT. Immunofixation electrophoresis was normal. There was only 0.6% plasma cells in the bone marrow. In conclusion, the auto-HSCT may be an effective treatment for multiple myeloma accompanied with amyloidosis in four limbs.
Amyloidosis ; complications ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; complications ; surgery ; Transplantation, Autologous

OBJECTIVETo explore the relationship of clinical features, therapeutic measures, laboratory findings, the origin of tumor cells as well as prognosis in Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSOne hundred and six patients with DLBCL were retrospectively assayed and followed up, the international prognostic index (IPI) score, Ann Arbor staging, ECOG score, the origin of tumor cells and different therapeutic methods were analyzed.

RESULTSAccording to the IPI, there were 61 cases (57.5%) with low-intermediate risk and 45 (42.5%) with intermediate-high risk. According to Ann Arbor staging, there were 8 phase I cases (7.5%), 16 phase II (15.0%), 54 phase III (51.0%) and 28 phase IV (26.5%). Twenty-five cases (23.6%) were accompanied with bone marrow invasion, 16 of them were diagnosed as lymphosarcoma cell leukemia; 38 cases with ECOG score ≥ 2; 67 cases (63.2%) had an increased LDH level; 59 cases (55.7%) had B symptom. The response rate (RR) for the whole group was 71.7%, the complete remission (CR) rate was 59.4% (63 cases), the partial remission (PR) rate was 12.3% (13 cases), the stable disease rate was 2.8% (3 cases) and the death rate was 27.4% (29 cases). The 4-year survival rate was 72.6%. Univariate analysis indicated that eight factors were related with prognosis (P < 0.05), including IPI score, Ann Arbor staging, ECOG score, the origin of tumor cells, LDH level, bone marrow invasion, different therapeutic methods and whether or not CR. Multivariate analysis showed that the origin of non-germinal center (HR = 4.24, P = 0.001), bone marrow invasion (HR = 2.08, P = 0.012), whether or not CR (HR = 2.72, P = 0.006) and therapy modality (HR = 2.58, P = 0.009) were significant factors for prognosis.

CONCLUSIONThe bone marrow invasion and the origin of tumor cells are independent risk factors for prognosis. The rituximab combined with chemotherapy can significantly improve the therapeutic effect of the DLBCL, and hematopoietic stem cell transplantation is the best choice for treating patients with DLBCL.

Adult ; Aged ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome ; Young Adult

As an essential metal for sustaining life, iron is involved in a number of metabolic processes, including DNA synthesis, electron transport, oxygen delivery, and so on. Iron metabolism involves the absorption, transport, and use of iron and is strictly regulated. Numerous studies have found a positive correlation between iron storage and the risk of tumors, such as colorectal carcinoma, hepatic cancer, renal carcinoma, lung cancer, and gastric cancer. In tumor cells, iron metabolism changes by several mechanisms, such as regulating the growth of tumor cells by transferrin, accelerating the uptake of iron by the overexpressions of transferrin receptors 1 and 2 (TfR1 and TfR2), synthesizing or secreting ferritin by some malignant tumor cells, and upregulating the level of hepcidin in patients with cancer. Some advances on diagnosis and treatment based on iron metabolism have been achieved, such as increasing the transfection and target efficiency of transferrin-polyethylenimine (PEI), inducing cell apoptosis by beta-guttiferin through interacting with TfR1.
Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antigens, CD ; genetics ; metabolism ; Antimicrobial Cationic Peptides ; biosynthesis ; genetics ; Apoptosis ; Cell Proliferation ; Doxorubicin ; pharmacology ; Ferritins ; metabolism ; physiology ; Hepcidins ; Humans ; Interleukin-18 ; pharmacology ; Iron ; metabolism ; physiology ; Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Receptors, Transferrin ; genetics ; metabolism ; Transferrin ; metabolism ; physiology ; Tumor Suppressor Protein p53 ; pharmacology

BACKGROUND:Nucleus pulposus cell apoptosis is the main pathological basis for intervertebral disc degeneration,and inflammation and peroxidation are important factors leading to apoptosis in the nucleus pulposus.Studies have shown that matrine has antioxidant,senescent,inflammatory and apoptotic effects,and may be a potential drug for the treatment of disc degeneration. OBJECTIVE:To investigate the effect of matrine on apoptosis of nucleus pulposus cells in rats with intervertebral disc degeneration by regulating the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway. METHODS:(1)Nucleus pulposus cells of rats at a logarithmic phase were randomly separated into a control group,a model group,a low-dose matrine group,a high-dose matrine group,an empty group,and a high-dose matrine+cGAS overexpression group.Except for the control group,cell models of intervertebral disc degeneration were established in the other groups through oxygen-glucose deprivation.At the same time of modeling,the low-dose and high-dose groups were treated with 0.4 and 0.8 mmol/L matrine,respectively,and the empty group was transfected with the empty plasmid,while the high-dose+cGAS overexpression group was treated with 0.8 mmol/L matrine with the transfection of the cGAS overexpression plasmid.After 24 hours of treatment,cell activity and apoptosis,intracellular levels of reactive oxygen species,superoxide dismutase,tumor necrosis factor α and interleukin 1β,and intracellular expression of apoptotic proteins and cGAS-STING pathway proteins were detected.(2)Sixty Sprague-Dawley rats were randomized into six groups(n=10 per group):control group,model group,low-dose matrine group,high-dose matrine group,empty group,and high-dose+cGAS overexpression group.After 12 weeks of modeling,60 and 120 mg/kg matrine were given by gavage in the low-dose and high-dose matrine groups,respectively(once a day),and the empty plasmid was injected into the tail vein in the empty group(2 times/week),while the high-dose+cGAS overexpression group was given 120 mg/kg matrine by gavage and injected with cGAS overexpression plasmid to the tail vein.Treatment in each group was given consecutively for 3 weeks.Samples were taken after drug administration and assayed for apoptosis,levels of reactive oxygen species,superoxide dismutase,tumor necrosis factor α and interleukin 1β,as well as apoptotic protein and cGAS-STING pathway protein expression. RESULTS AND CONCLUSION:Compared with the control group,in the model group,cell activity and superoxide dismutase levels were decreased(P<0.05),and apoptosis rate,levels of reactive oxygen species,tumor necrosis factor α and interleukin 1β,and the expression of cGAS,STING,cleaved caspase-3 and Bax proteins were elevated(P<0.05).Matrine dose-dependently ameliorated the above changes in each index due to cellular modeling(P<0.05),whereas cGAS overexpression partially antagonized the ameliorative effect of high-dose matrine.Similar results to the in vitro cellular experiments were obtained in animal experiments.These results indicate that matrine could inhibit inflammation and oxidative stress by blocking the cGAS-STING signaling,which in turn attenuates apoptosis and elevates the activity of nucleus pulposus cells in rats with intervertebral disc degeneration.