OBJECTIVETo observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap).

METHODSPregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA.

RESULTSCompared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P < 0.05, P < 0.01). Compared with the Bap model group, body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P < 0.05, P < 0.01). Ovary index and serum β-HCG increased in middle and high dose SE groups (P < 0.05, P < 0.01). The number of implantation obviously increased in the high dose SE groups (P < 0.01).

CONCLUSIONSE could reduce the embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene.

Animals ; Benzo(a)pyrene ; toxicity ; Chorionic Gonadotropin ; blood ; Embryo Implantation ; drug effects ; Female ; Ovary ; drug effects ; Plant Extracts ; pharmacology ; Pregnancy ; Progesterone ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; drug effects ; Schisandra ; chemistry ; Uterus ; drug effects

Drug resistance,tumor relapse and metastasis remain the main obstacles to the success of cancer treatments. Chemotherapies,targeted therapies and immunotherapies can successfully achieve remissions in cancer patients, but durable responses are rare. Although the mechanisms of diverse therapies vary,plasticity alteration of tumor and immune cells in response to therapy-induced tumor tissue injury and inflammation contributes to the development of drug resistance. This review summarizes research progress in the adaptive phenotypic plasticity of tumor cells and immune cells during tumor progression as well as the successful combination of targeted therapy and immunotherapy in cancer treatment to tackle resistance.

Objective To study the effect of TLR4 activation with LPS on BMP9-induced osteogenic differentiation of immortalized mouse embryonic fibroblasts ( iMEFs).Methods The activation of TLR4/NF-κB signaling path-way was detected by ICC.iMEFs were treated with LPS,BAY11-7082,Adnovirus GFP and BMP9.The early osteo-genic differentiation capability of iMEFs was detected by ALP staining and quantitative assay .The later osteogenic differentiation capability was detected by alizarin red S staining .The expression of later osteogenic differentiation marker gene OCN and OPN were detected by PCR and Western blot .The change of p-Smad1/5/8 was detected by Western blot.The expression of Runx2 and Dlx5 were detected by PCR and Western blot .Results LPS can effec-tively stimulate TLR4/NF-κB signaling pathway .TLR4 activation inhibited BMP 9-induced osteogenic differentiation . BMP9-induced osteogenic differentiation related gene and Smad 1/5/8 signaling activation were inhibited by TLR4 activation .The inhibition effect was partly reversed by BAY 11-7082 ( P<0.05 ) .Conclusions TLR4 activation with LPS can inhibit BMP9-induced osteogenic differentiation of iMEFs cells via NF-κB signaling pathway .

Objective To investigate the changes and clinical significance of serum lactate dehydrogenase (LDH),creatine kinase (CK),glutamate pyruvate transaminase (AST),and cerebrospinal fluid lactate dehydrogenase (CSF LDH) in adult patients with acute central nervous system infection.Methods The levels of myocardial enzymes (AST,LDH,and CK) in serum of 96 adult patients with acute intracranial infection in 7days and 39 healthy people were measured by Beckman automatic biochemical analyzer and enzyme rate assay,and CSF LDH level in 96 patients were measured simultaneously.Results (1) The serum myocardial enzymes (LDH,CK,and AST) of intracranial infection group (47 cases with viral encephalitis,30 cases with tuberculous meningitis,and 19 cases with purulent encephalitis) were significantly higher than those of normal control group (P ＜0.01).(2)The myocardial enzymes (LDH,and AST ) of patients with cerebral functional disorder were significantly higher than those of patients with normal cerebral function (P ＜0.05).(3)The levels of serum AST,LDH,and CK in the virus encephalitis group,serum AST and LDH in the purulent encephalitis group,and serum LDH in the tuberculous meningitis group were significantly higher than those in the control group (P ＜ 0.01).The CSF LDH level in the viral meningitis group was prominently lower than that in the tuberculous encephalitis group and purulent encephalitis group,respectively (P ＜0.01).(4) No correlations were found between CSF LDH and serum myocardial enzymes (P ＞0.05).Conclusions (1)There is significant change in the levels of serum LDH,CK,AST,and CSF LDH of adult patients with acute intracranial infection,especially in infected patients with cerebral functional disorder,and the change of LDH is the most obvious.(2)The levels of serum myocardial enzymes and CSF LDH are helpful to the differential diagnosis of intracranial infection in early stage,and judging the severity of the illness.

Objective: To investigate the effects of point thread embedding on the learning and memory of the vascular dementia(VD) model rats and the possible mechanisms. Methods: VD rat models were established by employing improved method of Pulsinelli's four-vessel occlusion,then the model rats were treated with point thread embedding.Morris maze test was used to evaluate the learning and memory of the rats.In vivo recording of long term potentiation(LTP) was performed in the dentate gyrus of hippocampus and changes in each experimental group were observed and compared after high-frequency stimulation(HFS).Results: Compared with models group,the results from the Morris tests in treated group(thread embedding group)enhanced significantly(P

Objective: To explore the structural domains of the CENP-E protein that interact with Mps1 protein.Methods: Two recombinant vectors named pEGFP-CENPE2(containing 674-1085 amino acids of CENP-E protein) and pEGFP-CENPE 3(containing 1200~2134 amino acids of CENP-E protein) were transfected into human embryo kidney 293(HEK293) cells respectively.The respective energy transfer efficiency(Ef) between either EGFP-CENPE2 and Mps1,or EGFP-CENPE3 and Mps1 were detected by FRET through selective photobleaching of the acceptors.Results: Both recombinant proteins expressed in HEK293 cells transfected by the recombinant plasmids were found to co-localize with the Mps1 protein as confirmed by confocal microscopy.The Ef between EGFP-CENPE3 and Mps1 protein was [(12.63?0.48)%,n=30] and that between EGFP-CENPE3 and Mps1 protein was [(3.17?0.21)%,n=30] as revealed by the results from FRET,the result of FRET was confirmed by co-Immunoprecipitate(CO-IP) method.When compared with that between the control and Mps1,the Ef between EGFP-CENPE3 and Mps1 was significantly higher(p

Objective To approach the clinical significance of Clara cell secretary protein(CCSP) in bronchial asthmatic children. Methods Serum were collected from 50 cases during asthmatic attacks, 22 asthmatic children who were in stable conditions, and 20 healthy children. Serum CCSP concentrations were measured by a human CCSP enzyme- linked immunosorbent assay (ELISA). Results Asthmatic children had significantly lower levels of CCSP in serum during asthmatic attacks(P

Objective To explore the role of Clara cell secretory protein(CCSP) in asthmatic children and compare the levels of CCSP in sera and induced sputum.Methods Thirty-four children with asthma who were in remission and 25 healthy controls were enrolled.Sera and hypertonic saline-induced sputum were obtained in asthmatic children,and sera alone were obtained in control subjects.The le-(vels) of CCSP were measured in sera and induced sputum by enzyme linked immunosorbent assay.Results Asthmatic children,compared with controls,had significantly lower concentration of CCSP in sera(P

Recent work indicates that an Aurora kinase inhibitor MK-0457 (VX-680), a small-molecule inhibitor of Aurora kinases A, B, C and BCR-ABL, FLT-3, JAK-2, can block the progression of cell growth cycle, causing apoptosis in a range of human tumors. MK-0457 has the activity against expressions of wild-type and mutated bcr-abl gene, including the T315I mutant, and can inhibit the activity of FLT-3, JAK-2 and their mutated types as well. Clinical applications suggest that the MK-0457 has therapeutic effect on the highly refractory CML and CML with poor prognosis, Ph(+) ALL with T315I mutant, relapse refractory AML and JAK-2 positive myeloproliferative diseases (MPD). The intensive preclinical studies and the on-going phase II clinical trials will open up a new vista of therapy for some hematological malignancies. This review focuses on the pharmacologic action of MK-0457 and its clinical trial as well as combined application.
Aurora Kinases ; Hematologic Neoplasms ; classification ; drug therapy ; Humans ; Piperazines ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Serine-Threonine Kinases ; antagonists & inhibitors

Acute Disease ; Adult ; Aged ; Angiography ; Female ; Humans ; Male ; Middle Aged ; Phlebography ; Thrombolytic Therapy ; Tomography, X-Ray Computed ; Venous Thrombosis ; diagnostic imaging ; drug therapy