Baculoviral IAP(inhibitor of apoptosis protein) gene was identified firstly in IAP gene family.The structurcal feature of baculoviral IAP genes are characterized BIR and RING domain;Despite similar to P35 in antiapoptotic function,baculovrial IAP and P35 differ in structure and mechnism of action.Phylogenetic analysis of IAP genes and lots of evidence sppport the origin of this viral gene by capture of a host gene early in the evolution of Lepidoptera.

In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.
Animals ; Brain Ischemia ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; Humans ; Inflammation ; drug therapy ; Medicine, Chinese Traditional ; Nervous System Diseases ; drug therapy

Objective To summarize the clinical features,diagnosis and treatment of autologous urologic neoplasms in renal transplant recipients.Methods A retrospective analysis on the clinical data of 25 renal transplant recipients was done in our center.The onset time of new neoplasms was between 29 to 72 months after transplantation,with an average of 48.2 months.Intermittent hematuria was the first symptom in 23 patients,and the rest two cases were diagnosed through routine examination. The pathological diagnoses of thee cases were renal carcinoma,which were treated by transperitoneal laparoscopic radical nephrectomy.Eight cases were diagnosed as having renal pelvic tumor,which was treated by radical resection for the renal pelvic carcinoma.Fourteen cases were diagnosed as having bladder cancer,which was treated by transurethral resection of bladder tumor (13 cases) or radical cystectomy (one case).All patients were subjected to surgical treatment.The dosage of MMF,CSA/Tacrolimus was decreased to 1/2-2/3 of their original dosage. Sirolimus was used in place of calcineurin inhibitors in four patients.Immunosuppressive regimes and adjuvant therapy were given after surgery treatment.Results Twenty-five patients were followed up for 12-84 months.Contralateral renal carcinoma combined with lung and chest multiple metastases occurred in one case after radical nephrectomy,who died after targeted therapy 6 months later.Two patients with lymph node metastasis died 14 months and 20 months after surgery respectively.The rest 22 patients were closely followed up,whose creatinine remained 98-163μmol/L.Conclusion More attention should be paid to patients with hematuria after renal transplantation to screen the autologous urinary neoplasms.Patients should be treated with surgical procedures,and immunosuppressive regimens should be adjusted postoperatively.

Objective To investigate the influence of chemotherapy combined with autophagy inhibitor on apoptosis and calreticulin (CRT) expression on colonic cancer cells. Methods The colon cancer cells HCT116 were taken as the target in the present study. The inhibition rates (IC50) of chemotherapeutics oxaliplatin, 5-Fu and SN-38 were assessed by MTT assay. The changes in CRT expression on the membrane of HCT116 and apoptosis were determined with flow cytometry before and after treatment with chemotherapeutics. CRT location in HCT116 was detected by fluorescent immunoassay before and after treatment with chemotherapeutic agents. The influence on HCT116 autophagy was determined by Western blotting after treatment with these chemotherapeutic agents. The changes in CRT expression on HCT116 membrane and apoptosis were determined with flow cytometry before and after treatment with the chemotherapeutics combined with autophagy inhibitor chloroquine (CQ). Results The ratio of apoptosis and membrane expression of CRT were elevated 12 hours after treatment with Oxaliplatin, 5-Fu and SN- 38, but without statistical significance. Fluorescent immunoassay showed a transposition of CRT from cytoplasm to the membrane after oxaliplatin treatment. Western blotting revealed that oxaliplatin, 5Fu and SN38 induced autophagy of HCT116 cells, and the autophagy was inhibited by the addition of CQ. Flow cytometric analysis indicated that the percentages of annexin V+ cells and membrane expression of CRT were higher after treatment with the chemotherapy agents combined with CQ. The upregulation of CRT expression on membrane was obviously higher after treatment with oxaliplatin combined with CQ than that before the treatment with these agents (P=0.027). Conclusion Oxaliplatin combined with CQmay increase the apoptosis rate of HCT116 cells and upregulate CRT expression in the membrane.

OBJECTIVETo study the effects of drug plasma of musk and olibanum (DP-M&O) on the release of inflammatory cytokines from monocytes and the expressions of the proteins associated with inflammation of prostatic or endothelial cells induced by prostate antigen (PAg) stimulation.

METHODSWe prepared DP-M&O using SD rats and monocytes and PAgs using BALB/c mice. We pre-treated the monocytes with DP-M&O at the gradient concentrations of 0, 2.5, 5, 10, and 20% for 1 hour, activated them with PAgs, and then cultured them for 96 hours, followed by detection of the release of inflammatory cytokines. We co-cultured the prostate RWPE-1 cells with the endothelial EA. hy926 cells, pre-treated them with the same gradient concentrations of DP-M&O as above for 1 hour, activated with PAgs, and cultured for 96 hours. Then we determined the expression levels of the proteins associated with inflammation of RWPE-1 and EA. hy926 cells by Western blot.

RESULTSDP-M&O decreased the levels of TNF-alpha, IL-1beta, IL-6, and IL-8 and increased that of IL-10 in a concentration-dependent manner. Significant differences were found between the 20% P-M&O and PAg groups in the release of the inflammatory cytokines TNF-alpha (70.8 +/- 22.3 vs. 277.1 +/- 65.5, P < 0.01) , IL-113 (277.5 +/- 22.6 vs. 630.4 +/- 89.7, P <0.01), IL-6 (232.7 +/- 62.7 vs. 994.2 vs. 182.3, P < 0.01), IL-8 (227.3 +/- 79.2 vs. 769.3 +/- 284.1, P < 0.01), and IL-10 (640.2 +/- 201.2 vs. 271.1 +/- 55.8, P < 0.01). Compared with the PAg group, the 10 and 20% P-M&O groups showed remarkable decreases in the protein expression of MCP-1/CCL2 in the RWPE-1 cells (1.12 +/- 0.34 vs. 0.56 +/- 0.11 and 0.34 +/- 0.08) and that of VCAM-1 in the EA. hy926 cells (0.94 +/- 0.22 vs. 0.52 +/- 0.17 and 0.38 +/- 0.12) (P < 0.05 or 0.01).

CONCLUSIONThe compatibility of musk and olibanum can decrease the expression of MCP-1/CCL2 in prostate cells and VCAM-1 in vascular endothelial cells, blocking the adhesion of leucocytes and suppressing inflammatory response.

Animals ; Blotting, Western ; Cytokines ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Fatty Acids, Monounsaturated ; pharmacology ; Frankincense ; pharmacology ; Inflammation ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; Male ; Mice ; Mice, Inbred BALB C ; Monocytes ; drug effects ; metabolism ; Prostate ; cytology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Objective: To compare clinical characteristics and prognosis between patients with primary (PTL) and secondary thyroid lymphoma (STL) . Methods: A retrospective analysis was performed on 46 patients with thyroid lymphoma (PTL 19, STL 27) from January 2002 to October 2018. Results: ①PTL group included 4 males and 15 females, with a median age of 57 years. The STL group included 10 males and 17 females, with a median age of 61 years. Diffuse large B-cell lymphoma (DLBCL) was the main pathological subtype in both PTL and STL groups, with 14 cases (73.7%) and 20 cases (74.1%) respectively. In terms of clinical manifestations, goiter was the most common symptom in PTL patients 100.0% (19/19) , while 29.6% (8/27) STL had goiter (P<0.001) . The incidences of increased thyroglobulin antibody (TRAb) /thyroid peroxidase antibody (TPO) were 81.3% (13/16) in PTL group and 43.8% (7/16) in STL group (P=0.028) respectively. Concerning the clinical features of patients, only two PTL patients (10.5%) with advanced Ann Arbor stage (Ⅲ/Ⅳ) , while 21 (77.8%) STL experienced advanced Ann Arbor stage (P<0.001) . Elevated serum β(2)-MG were appeared in 1 (7.1%) PTL and 9 (47.4%) STL patients (P=0.013) , and advanced IPI score (3-5) was more common in STL than PTL (59.3% vs 5.3%, P<0.001) . ②Among the 17 PTL patients who received treatments, 15 (88.2%) achieved remission; as for STL patients received treatments, 23/25 (92.0%) were in remission. The 5-year overall survival (OS) rates of PTL (n=17) and STL groups (n=25) were (87.4±8.4) % and (70.0±13.1) % (P=0.433) respectively. ③The 5-year OS rate in 41 patients with B-cell thyroid lymphoma was (81.1±7.5) %. Univariate analysis showed that IPI score of 3-5 (P=0.040) and high level of serum IL-8 (P=0.022) were significantly associated with poor outcome. Conclusion: DLBCL was the most common subtype in both PTL and STL, and goiter was the major symptom in PTL. IPI score of 3-5 and high level of serum IL-8 were unfavorable prognostic factors for patients with B-cell thyroid lymphoma.
Autoantibodies/blood* ; Female ; Goiter/etiology* ; Humans ; Interleukin-8/blood* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Thyroid Gland/pathology* ; Thyroid Neoplasms/secondary*

Aim To investigate the protective effect of berberine(BBR)on mice with unilateral ureteral obstr-uction(UUO)and explore its mechanism.Methods C57BL/6 mice were randomly divided into the sham group,UUO group,and BBR treatment groups(50,100 and 200 mg·kg-1),with eight mice in each group.Except the sham group,the other groups were subjected to left ureteral ligation to establish the UUO model.Af-ter modeling,the mice in the sham and UUO groups were fed normal saline,and the mice in the BBR treat-ment groups were fed(50,100,200)mg·kg-1 BBR by gavage for 14 days,respectively.Biochemical analy-zer was employed to detect the levels of serum creati-nine(Scr)and blood urea nitrogen(BUN).HE,Mas-son,TUNEL and immunohistochemical staining were used to observe the pathological changes of renal tis-sue.ELISA was employed to detect the expression of pro-inflammatory cytokines in renal tissue homogenate.Western blot was used to detect the protein levels of NF-κB p65,TGF-β1 and CTGF in mouse kidney.Re-sults Compared with the UUO group,the levels of Scr and BUN in the BBR group were significantly reduced.Renal injury and interstitial fibrosis were alleviated.The expression of pro-inflammatory cytokines decreased in kidney.The expression of NF-κB p65,TGF-β1 and CTGF decreased.All results showed some degree of dose dependence.Conclusion Berberine has a sig-nificant protective effect on unilateral ureteral obstruc-tion mice,and the mechanism may be that BBR has the potential to inhibit NF-κB p65/TGF-β1/CTGF signa-ling pathway,thus reducing renal inflammation and fi-brosis.

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.
Administration, Oral ; Animals ; Biological Availability ; Biomedical Research ; methods ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Temperature

OBJECTIVETo investigate the effects of the combination of musk and olibanum on the tight junction protein expressions in prostatic epithelial cells of normal and chronic prostatitis (CP) rats.

METHODSEighty male SD rats were randomly divided into 8 groups of equal number: normal control, normal musk, normal olibanum, normal musk + olibanum, CP model control, CP model musk, CP model olibanum, and CP model musk + olibanum. At 60 days after modeling, the rats in the control, musk, olibanum, and musk + olibanum groups were treated intragastrically with normal saline, musk (0.021 g per kg body weight per day), olibanum (1.05 g per kg body weight per day), or musk + olibanum respectively, all for 3 days. Then, all the rats were sacrificed and their prostate tissues harvested for detection of the expressions of the tight junction proteins Claudin-1, Claudin-3, Occludin, and ZO-1 in the prostatic epithelial cells by immunohistochemical staining.

RESULTSIn the CP models, only the expression of Claudin-1 was significantly increased. In the normal rats, the expression of Claudin-1 was remarkably upregulated after treated with musk (824.6 ± 393.3, P < 0.05), olibanum (982.0 ± 334.0, P < 0.05), and musk + olibanum (1088.1 ± 640.2, P < 0.01); that of Claudin-3 was elevated markedly by olibanum (1 009.5 ± 243.6, P < 0.05) and insignificantly by musk (597.5 ± 80.7), but the increasing effect of olibanum was reduced by musk + olibanum (678.4 ± 255.1). No statistically significant differences were found in the expression of Occludin among the rats treated with musk (693.0 ± 424.8), olibanum (732.1 ± 302.0), and musk + olibanum (560.2 ± 202.3), or in that of ZO-1 in the animals treated with musk (290.0 ± 166.8) and olibanum (419.7 ± 108.1), but the latter was markedly decreased in the musk + olibanum group (197.7 ± 98.2, P < 0.05). In the CP rat models, both the expressions of Claudin-1 (823.0 ± 100.1, P < 0.01) and Occludin (1160.0 ± 32.2, P < 0.05) were significantly increased. The expression of Claudin-1 was remarkably down-regulated by musk (764.9 ± 179.0), olibanum (468.4 ± 220.4), and musk + olibanum (335.1 ± 204.0) (all P < 0.05), but that of Claudin-3 up-regulated by musk (744.6 ± 94.5) and olibanum (700.1 ± 223.7) (both P < 0.05). The expression of Occludin was reduced by musk (615.0 ± 221.0), olibanum (749.6 ± 321.7), and musk + olibanum (505.8 ± 523.7), while that of ZO-1 increased by olibaum (443.2 ± 44.9) and decreased by musk + olibanum (213.5 ± 24.9, P < 0.05).

CONCLUSIONIn physiological and pathological conditions, the combination of musk and olibanum acts on the expressions of tight junction proteins in prostate epithelial cells in a selective and dual-targeting manner, promoting their permeability by down-regulating the expression of ZO-1 and maintaining their structural stability by regulating the expressions of Claudin-1, Claudin-3, and Occludin.

Animals ; Claudins ; metabolism ; Down-Regulation ; Epithelial Cells ; drug effects ; Fatty Acids, Monounsaturated ; chemistry ; Frankincense ; chemistry ; Male ; Occludin ; metabolism ; Prostate ; cytology ; Prostatitis ; Rats ; Rats, Sprague-Dawley ; Tight Junction Proteins ; metabolism ; Up-Regulation

OBJECTIVETo evaluate the relationship of hypoxia-inducible factor (HIF)-1alpha expression with chemotherapy response in gastric cancer and its clinical outcome.

METHODSLeucovorin (CF) and 5-fluorouracil (5-FU) in combination with oxaliplatin (L-OHP) were used in 52 patients with gastric carcinoma (GC) at advanced stage. CF 200 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. 5-FU 1500 mg/m(2) was continuously intravenous drop for 46 h at day 1 and day 14. L-OHP 85 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. Four-week was one cycle. All the patients received 4 cycles of chemotherapy at least. Chemotherapy response and clinical outcome were evaluated. Immunohistochemistry was used to examine the protein expressions of HIF-1alpha, P-gp and MRP4 by tissue microarray in GC. Twenty-seven normal gastric tissue samples were used as control group.

RESULTSThe positive expression rates of HIF-lalpha, P-gp and MRP4 in tumor samples were 53.9%, 51.9% and 57.7% respectively, which were significantly higher than those in normal gastric tissues (0, 18.5% and 14.8% respectively) (P<0.05). In cases with positive expression of HIF-lalpha, the response rate was 14.3%; whereas in cases with negative expression of HIF-1alpha, the response rate was 50.0%. There was significant difference between two groups (P<0.05). In patients of HIF-1alpha positive expression,the median progression-free survival time was 4.7 months,the median survival time was 8.8 months, and 1-year, 2-year survival rates were 37.5% and 21.5% respectively. In patients of HIF-1alpha negative expression, the median progression-free survival time was 8.4 months, the median survival time was l2.6 months, and 1-year, 2-year survival rates were 51.2% and 33.5% respectively. There were significant differences between two groups (P<0.05).

CONCLUSIONHIF-1alpha expression may be a useful indicator to predict the chemotherapy response and clinical outcome in gastric carcinoma.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Middle Aged ; Prognosis ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; Survival Rate