Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.

Piperis Fructus is the dried nearly ripe or ripe fruit of Piperaceae, which is an important spice material and a traditional Chinese medicine (TCM), it is widely used in the world. It is recorded to possess the efficacy of warming spleen and stomach for dispelling cold, depressing Qi and dissolving phlegm. Piperis Fructus mainly contains amide alkaloids with piperine as the main ingredient and volatile oil dominated by monoterpenoids and sesquiterpenoids, which have a wide range of biological activities, such as anti-cancer, anti-oxidation, anti-inflammatory, etc. By referring to relevant papers at home and abroad, the researches on chemical compositions from different parts and pharmacological effects of Piperis Fructus in recent 5 years were summarized and analyzed. It was found that Piperis Fructus has great potential for drug development as a TCM with homology of medicine and food, which can provide a reference for further research and comprehensive utilization of Piperis Fructus.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients’ baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.
Blood Component Removal* ; China* ; Colitis, Ulcerative* ; Cytokines ; Granulocytes* ; Humans ; Inflammation ; Leukocytes ; Monocytes* ; ROC Curve ; Sensitivity and Specificity ; Treatment Outcome ; Ulcer*

Scorpion toxin BmK AngM1 has been reported to have a strong analgesic effect. However, its anti-inflammatory activity was unknown. In this study, the recombinant BmK AngM1 (rBmK AngM1) was expressed in Escherichia coli BL21 trxB (DE3). The purified rBmK AngM1 was obtained efficiently through the IMPACT^TM-TWIN system. The anti-inflammatory activity of the recombinant protein was investigated. In order to improve the anti-inflammatory activity of rBmK AngM1, the potential active sites (Y5, Y42, R58) were substituted with different amino acids. The results showed that rBmK AngM1 and its mutants all have significant anti-inflammatory activity. The activities were significantly increased in the single mutant R58N and mutants Y5F/R58N, Y42F/R58N over the wild type protein. The data suggest that position 58 in BmK AngM1 plays a functional role in the anti-inflammatory activity. This study lays a foundation for the protein engineering design of BmK AngM1 to improve its pharmacological activity.

BACKGROUNDRecent studies have shown that interleukin-3 receptor alpha (CD123) is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis. The expression of CD123 may also be high in patients with myelodysplastic syndrome (MDS). In this study, the expression and clinical significance of CD123 and granulocyte colony stimulating factor (G-CSF) receptor (CD114) on the bone marrow cells of patients with MDS were investigated to explore the molecular marker of the malignant clone of MDS.

METHODSForty-two patients with MDS, who were diagnosed in the Hematological Department of General Hospital of Tianjin Medical University from 2008 to 2009, and twelve normal controls were enrolled in this study. Fluorescence activiated cell sorter (FACS) was used to measure the expression of CD123 on CD34(+)CD38(-) cells and CD114 on CD34(+) cells of the bone marrow of these patients and controls and the clinical significance was analyzed. The expression of CD114 on CD123(+)CD34(+)CD38(-) cells was further measured to explore the molecular marker of the malignant clone in MDS.

RESULTSMDS patients displayed significantly higher proportion of CD34(+)CD38(-)/CD34(+) ((14.03 +/- 5.27)%) than normal controls ((7.70 +/- 4.36)%, P < 0.05). The expression rate of CD123(+)CD34(+)CD38(-)/CD34(+)CD38(-) was significantly higher in MDS patients ((48.39 +/- 28.15)%) than that in normal controls ((8.75 +/- 11.71)%, P < 0.01). The expression level of CD123 was significantly correlated with the proportion of bone marrow blasts (r = 0.457, P < 0.05). The expression rate of CD114(+)CD34(+)/CD34(+) was lower in MDS patients ((33.05 +/- 21.71)%) than that in normal controls ((38.99 +/- 19.07)%) but was not statistically significant (P > 0.05). The expression of CD114 on CD123(+)CD34(+)CD38(-) cells ((34.82 +/- 29.58)%) was significantly lower than that on CD123(-)CD34(+)CD38(-) cells ((53.48 +/- 27.41)%) of MDS patients (P < 0.05).

CONCLUSIONSMDS patients displayed higher proportion of CD34(+)CD38(-)/CD34(+) than normal controls. CD123 was highly expressed in the bone marrow of the patients with MDS, significantly correlated with the proportion of bone marrow blasts, and thus might be the marker of MDS malignant clone. CD123(+)CD34(+)CD38(-) cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responds worse to G-CSF in vitro and in vivo.

ADP-ribosyl Cyclase 1 ; metabolism ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Bone Marrow Cells ; metabolism ; Cells, Cultured ; Female ; Humans ; Interleukin-3 Receptor alpha Subunit ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; Receptors, Granulocyte Colony-Stimulating Factor ; metabolism ; Young Adult

OBJECTIVETo investigate whether low molecular weight heparin (LMWH) may suppress the expression and secretion of vascular endothelial growth factor (VEGF) from tumor cells in vitro and inhibit the VEGF-induced proliferation of human tumor vascular endothelial cells.

METHODSHuman lung cancer cell line A549, human liver cancer cell line HepG2, human colon carcinoma cell lines HCT116 and HCT8 were used in this study. The expression levels of VEGF and TNF-alpha (tumor necrosis factor-alpha) in the tumor cells with or without pretreatment of LMWH/heparin were measured by standard sandwich ELISA technique. The VEGF mRNA level of HepG2 cells cultured with or without LMWH/heparin was determined by RT-PCR and real time PCR. Human umbilical vein endothelial cells (HUVEC) were cultured in tissue culture medium (TCM) with or without LMWH/heparin for 3 days. Then non-radioactive cell proliferation assay (MTS) kit and cell cycle assay by flow cytometry were performed to measure the proliferation of HUVEC.

RESULTSThe VEGF levels in the control, LMWH, and heparin groups of the pulmonary adenocarcinoma cell line A549 were (1045.89 +/- 165.30) pg/ml, (782.45 +/- 67.17) pg/ml and (916.54 +/- 71.25) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups of the colon adenocarcinoma cell line HCT116 were (955.76 +/- 51.14) pg/ml, (822.89 +/- 142.39) pg/ml and (951.77 +/- 188.22) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the colon adenocarcinoma cell line HCT8 were (1290.62 +/- 41.23) pg/ml, (1063.34 +/- 63.82) pg/ml and (1257.14 +/- 11.40) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the liver cancer cell line HepG2 were (1083.00 +/- 134.35) pg/ml, (758.00 +/- 84.85) pg/ml and (874.00 +/- 22.62) pg/ml, respectively. The VEGF expression levels in the above mentioned cell lines cultured in TCM were significantly reduced in the LMWH-treated groups compared with that of the control group (P < 0.05). But the level of TNF-alpha in TCM-cultured cells was unaffected by LMWH. The VEGF mRNA was reduced in the LMWH-treated HepG2 cell line. Moreover, TCM exhibited stimulating effect on proliferation of HUVEC and the effect was significantly impaired by LMWH treatment. Flow cytometric analysis revealed that LMWH treatment arrested HUVECs at the G1 phase of cell cycle.

CONCLUSIONLMWH can suppress the expression and secretion of VEGF by tumor cell lines and therefore have a potential inhibiting effect on angiogenesis induced by VEGF.

Adenocarcinoma ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media, Conditioned ; Endothelial Cells ; cytology ; HCT116 Cells ; Hep G2 Cells ; Heparin ; pharmacology ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; secretion

The aim of this study was to explore the changes in cellular senescence related indexes of bone marrow mesenchymal stem cells (BMMSCs) after total body irradiation (TBI). At different time points after 4 Gy irradiation, BMMSCs were isolated from male C57BL/6 mice and cultured. Morphology, senescence-associated beta-galactosidase (SA-beta-gal) staining and cell cycle analysis were used to evaluate the changes in BMMSCs at cellular level while real-time RT-PCR was used to detect the alterations in senescence related gene expression including p16INK4a, p21Cip1/Waf1, p53 and TGF-beta1. The results showed that within 4 weeks after exposure to 4 Gy TBI, the morphology of BMMSCs and the expression level of SA-beta-gal were not significantly changed, the cellular senescence-related cell cycle arrest was not occurred and the senescence related gene expression level was not increased. It is concluded that at the early stage after 4 Gy TBI, the related molecular level of cellular senescence in BMMSCs is not changed.
Animals ; Bone Marrow Cells ; cytology ; radiation effects ; Cells, Cultured ; Cellular Senescence ; radiation effects ; Male ; Mesenchymal Stromal Cells ; cytology ; radiation effects ; Mice ; Mice, Inbred C57BL ; Whole-Body Irradiation

OBJECTIVETo evaluate the effect and safety of BCG vaccine on initially treated pulmonary tuberculosis and its controlling effect on multidrug-resistant tuberculosis.

METHODSAll 360 volunteers with initially treated pulmonary tuberculosis of positive smear and culture were divided into immunotherapy group (180 cases, also BCG group) and control group (180 cases) at random pair. The patients in BCG group were treated with chemotherapy of a regimen of 2HRZ/2HR and immunotherapy with BCG for 4 months,and the first BCG vaccine was given a month after chemotherapy. Meanwhile, the patients in the control group were treated with chemotherapy of 2HRZ/4HR only.

RESULTS(1) The negative conversion rate of sputum smear in BCG group was 98.3% (177/180), and it was 97.2% (175/180) in control group. There was no significant difference between the two groups both at the ends of 4 and 6 months after treatment (chi2 = 0.1278, P > 0.05). (2) The positive conversion rate of sputum smear in BCG group was 2.3% (4/177), and it was 6.9% (12/175) in control group followed up for 5 years. The successful rate was 96.1% (173/180) in BCG group, and it was significantly higher than that of 90.6% (163/180) in control group (chi2 = 4.4643, P < 0.05). (3) In the 5-year follow up, bacteriologic result was similar to that of X-ray. (4) The occurrence rate of multidrug-resistant tuberculosis was 2.3% (4/177) in BCG group,significantly lower than that of 7.3% (13/178) in the control group (chi2 = 4.9513, P < 0.05).

CONCLUSIONAs an adjunct chemotherapy,immunotherapy with BCG vaccine should be helpful for patients with initially treated pulmonary tuberculosis. It would further strengthen the effects of chemotherapy and reduce the occurrence rate of multidrug-resistant tuberculosis.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Aged ; Antitubercular Agents ; therapeutic use ; BCG Vaccine ; therapeutic use ; Child ; Female ; Follow-Up Studies ; Humans ; Immunotherapy, Active ; Male ; Middle Aged ; Tuberculosis, Multidrug-Resistant ; prevention & control ; Tuberculosis, Pulmonary ; therapy

To investigate the effect of irradiation on the quantity and osteogenesis potential of BMMSCs and to explore the response of them in the irradiation stress and its contribution to long-term effects of radiation-induced bone and hematologic injury, a total body irradiation (TBI) murine model was adopted. The number of CFU-F and cell cycle profile of BMMSCs were analyzed at different time points before and after TBI. Osteogenic differentiation was evaluated by Von Kossa staining, expressions of osteogenesis-related genes and transcriptional coactivator with PDZ-binding motif (TAZ) were detected by real-time RT-PCR. The results showed that the number of CFU-F decreased greatly at day 28 after TBI. At day 3 after TBI, more cells entered cell cycle and the osteogenesis potential was greatly enhanced followed by recovery of cell cycle distribution and significant defect in osteoblast differentiation respectively, meanwhile the expression of TAZ was changed. It is concluded that TBI results in the reduction of bone marrow mesenchymal stem/progenitor cell pool and alters the osteogenesis potential of BMMSCs, which is related to the change of TAZ expression.
Animals ; Bone Marrow Cells ; cytology ; radiation effects ; Colony-Forming Units Assay ; Dose-Response Relationship, Radiation ; Male ; Mesenchymal Stromal Cells ; cytology ; radiation effects ; Mice ; Mice, Inbred C57BL ; Osteogenesis ; radiation effects ; Whole-Body Irradiation