Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

ObjectiveTo observe the effects of bone marrow stromal cells (BMSCs) on vessel endothelial cells proliferation and microvessel formation in vitro.MethodsBMSCs and brain vessel endothelial cells were separated from adult and divided into co-culture group of BMSCs and endothelial cells, medium group of BMSCs, comparison group. Endothelial cells proliferation and microvessel formation were observed. ResultsEndothelial cells were promoted to proliferate and formate the microvessel in medium group and co-culture group. And the effect was prominence in co-culture group.ConclusionBMSCs can promote the proliferation and microvessel formation of endothelial cells.

Objective To examine the expression of recombinant cytolethal distending toxin(CDT)produced by Actinobacillus actinomycetemcomitans(Aa).Methods CDT encoding gene cdtABC was amplified by PCR.Through TA clone and restriction endonuclease digestion,gene cdtABC and vector pQE60 were ligated to form pQE60-cdtABC expression system which transformed into competent cells.Protein expression was induced by IPTG and examined by SDS-PAGE and Western-blotting.Results Random colony PCR of pQE60-cdtABC transformed cells demonstrated that all strains contained cdtABC gene.The DNA sequence was blast with cdtABC gene from GenBank and 99%homology was obtained.SDS-PAGE and Western-blotting confirmed that recombinant CDT was obtained.Conclusions CDT protein expression system was reconstructed and recombinant protein was obtained.

OBJECTIVETo explore the role of Xuebijing Injection (XBJI) in inhibiting inflammatory factors associated with anoxia/reoxygenation myocardial inflammatory response of rats.

METHODSTotally 36 healthy male Sprague-Dawley rats, 280 ± 30 g were randomly divided into six groups, i.e., the normal control group (N group), the balanced perfusion group (BP group),the model group (M group),the low dose XBJI group (XBJI(L) group), the middle dose XBJI group (XBJI(M) group),and the high dose XBJI group (XBJI(H) group), 6 in each group. The myocardial anoxia/reoxygenation rat model was established by Langendorff isolated heart perfusion. The concentration of TNF-α in the myocardial tissue was detected by ELISA. The expression of nuclear factor kappa B p65 (NF-κB p65) protein and Toll like receptor 4 (TLR4) protein were detected using Western blot. The expression of NF-κB p65 mRNA and TLR4 mRNA was detected by RT-PCR. Ultrastructural changes of anoxia-reoxygenation rats' heart muscle were observed under transmission electron microscope.

RESULTSCompared with the M group,the TNF-α concentration, expression levels of NF-κB p65 protein and mRNA, TLR4 protein and mRNA decreased to various degrees in the XBJI(L) group, the XBJI(M) group, and the XBJI(H) group. The TNF-α expression level decreased most significantly in the XBJI(L), group (P < 0.01), while other indices decreased most obviously in the XBJI(M) group (P < 0.01, P < 0.05). Expression levels of NF-κB p65 and TLR4 protein were obviously lower in the XBJI(M) group than in the XBJI(L) group (P < 0.05). There was no statistical difference in other indices among the three XBJI groups (P > 0.05). Myocardial fibers were loose and broken with disappearance of transverse striation, and mitochondrial cristae was dissolved and severely damaged in the M group. The aforesaid condition was improved after treated by XBJI, with the most obvious effect obtained in the XBJI(M) group.

CONCLUSIONSDifferent doses of XBJI could attenuate inflammatory reactions after myocardial anoxia/reoxygenation rats' heart muscle through inhibiting TLR4-NF-κB-TNF-α signal transduction pathway. The best effect could be obtained by 4 mL/100 mL XBJI.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Hypoxia ; Male ; Myocardium ; metabolism ; Myocytes, Cardiac ; NF-kappa B ; metabolism ; Oxygen ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha ; metabolism

Objective To evaluate the possible interactions among different impact factors possibly affecting the treatment efficacy of 131I in Graves′ disease (GD). Methods Six hundred and thirty two GD patients that had been treated by 131I, with or without antithyroid drugs (ATD), were included in this study. The impact factors were pre-defined as age (x1), sex (x2), mass of thyroid (x3), course of disease (x4), initial symptom (x5), condition of disease (x6), ATD treatment duration (x7), effective half life time (x8), maximum 131I uptake rate (x9), total dose of 131I (x10), dose of 131I per gram of thyroid (x11), TRAb (x12), TSI (x13), TgAb (x14), and thyroid microsomal antibody(TMAb) level(x15). Interactions among different impact factors were studied by t-test, χ2 test and multi-variant logistic regression. Results Age, mass of thyroid, ATD treatment duration, maximum 131I uptake rate, dose of 131I per gram of thyroid tissue and TSI level were identified as independent impact factors affecting the 131I treatment efficacy on GD (χ2=6.908, t=-4.063, χ2=13.558, t=-2.553, t=4.528, χ2=9.716, all P<0.05) by uni-variant and multi-variate analyses. Loglinear and general linear model analyses showed that there existed multiple multiplicative and additive interactions among the factors of age, mass of thyroid, ATD treatment duration and maximum 131I uptake rate (likelihood χ2=8.176, P>0.05; F=2.928, 1.992, 2.629, 2.215, all P<0.05), which indicated that the treatment efficacy with co-existing multiple factors was not equal to simple summation of single factors. Conclusions The interactions among multiple factors can cause indi-rect effect on 131I treatment, which might guide the prescription of 131I dosage for GD treatment.

OBJECTIVEThe ability of oral bacteria to adhere to tooth surface is associated with their pathogenicity. The objective of this study was to compare the ability of 4 strains of periodontal pathogens attaching to collagen-treated hydroxyapatite (C-HA) beads in order to evaluate the ability of the main periodontal pathogens to form the biofilm on root surface.

METHODSThe binding amount and binding percentage of 4 strains to C-HA were measured and compared by 3H-labeled binding assay. 4 strains of periodontal pathogens were Fusobacterium nucleatum (F. nucleatum) ATCC 10953, Porphyrin gingivalis (P. gingivalis) ATCC 33277, Prevotella intermedia (P. intermedia) ATCC 25611 and Hemophilic actinomycetemcomitans (H. actinomycetemcomitans) ATCC 29523.

RESULTSThe differences of the percentage of relative adherence between F. nucleatum ATCC 10953 and P. gingivalis ATCC 33277, as well as between H. actinomycetemcomitans ATCC 29523 and P. intermedia ATCC 25611 could not be observed. However, the percentage of relative adherence of F. nucleatum ATCC 10953 and P. gingivalis ATCC 33277 was higher than that of P. intermedia ATCC 25611 and H. actinomycetemcomitans ATCC 29523 (P<0.001), no matter cultured 24 h or 48 h. No significant difference of the percentage of the relative adherence of each stain between 24 h and 48 h cultured time could be found.

CONCLUSIONF. nucleatum and P. gingivalis exhibited strong binding ability to C-HA. Their adherence to root surface may play an important role in their local aggregation, biofilm formation during the development and recurrence of the periodontitis.

Aggregatibacter actinomycetemcomitans ; Bacteria ; Collagen ; Durapatite ; Fusobacterium nucleatum ; Humans ; Periodontitis ; Porphyromonas gingivalis ; Prevotella intermedia

OBJECTIVETo observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence.

METHODSTwenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment.

RESULTSThe body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05).

CONCLUSIONMoxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.

Adolescent ; Body Height ; Child ; Estradiol ; metabolism ; Exercise Therapy ; Female ; Growth Disorders ; metabolism ; physiopathology ; therapy ; Human Growth Hormone ; metabolism ; Humans ; Kidney ; physiopathology ; Male ; Moxibustion ; Testosterone ; metabolism ; Treatment Outcome

OBJECTIVETo investigate the relationship between plasma levels of fibrinogen, the-beta455 G/A fibrinogen gene polymorphism and the severity of periodontal inflammation and to explore the possible role of fibrinogen in the association of periodontitis with coronary heart disease (CHD).

METHODSA total of 121 patients with moderate to severe periodontitis and periodontally healthy and gingivitis controls were enrolled in the study. Peripheral blood samples were collected and the plasma fibrinogen levels were determined by the clotting method of Clauss. Polymerase chain reaction and restriction fragment length polymorphism analysis with Hae III were used to examine the -beta455 G/A fibrinogen gene polymorphism.

RESULTSFibrinogen levels were significantly higher in moderately or severely chronic periodontitis patients [(3.45 +/- 0.68) g/L] than periodontally healthy and gingivitis controls [(2.47 +/- 0.42) g/L, P < 0.001]. The carrier status of the A allele at position -455 in the beta fibrinogen gene was associated with elevated fibrinogen levels and the frequency of the-A455 allele in the beta fibrinogen gene in the patient group was significantly higher than in the control group (P = 0.032). Carriers of the -A455 allele were about 3-fold more likely to have moderate or severe periodontitis as compare to individuals without the -A455 allele( OR = 3. =135, P= 0.008).

CONCLUSIONSFg-beta455 G/A polymorphism may contribute to the elevated plasma fibrinogen levels and put individuals at higher risk of having severe periodontitis. As the independent risk factor of CHD, fibrinogen levels and Fg-beta455 G/A polymorphism may play a role in the pathogenesis of periodontitis.

Adult ; Alleles ; Case-Control Studies ; Chronic Periodontitis ; genetics ; Coronary Disease ; genetics ; Female ; Fibrinogen ; analysis ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.

METHODSOut-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.

RESULTSAfter the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.

CONCLUSIONShort-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.

Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Male ; Metformin ; therapeutic use ; Sulfonylurea Compounds ; therapeutic use ; Treatment Outcome

OBJECTIVEPorphyromonas gingivalis (P. gingivalis) is considered to be major putative periodontal pathogens. The purpose of the study was to evaluate P. gingivalis and clinical effects of scaling and root planning (SRP) in 20 subjects after 3 months.

METHODSTwenty periodontitis patients were selected. The mean age was (44.33 +/- 13.86) years old. Clinical assessments of probing depth (PD), clinical attachment loss (CAL) and bleeding on probing (BOP) were made prior to SRP and at 3 months post-therapy. Subgingival plaque samples were taken at each visit and analyzed using TaqMan real-time polymerase chain reaction for the presence and levels of P. gingivalis. The quantification for P. gingivalis was also performed with the help of the species-specific primers/probes and the serial dilution of the plasmid standards.

RESULTSMean probing depth, mean clinical attachment loss and bleeding on probing showed significant reduction at 3 months (P<0.001). The prevalence and level of P. gingivalis were significantly reduced after SRP (P<0.001). A positive correlation was found between the numbers of P. gingivalis and PD at baseline (P<0.001). There were no correlation between the initial level of P. gingivalis at baseline and the clinical improvement after therapy. But the number of P. gingivalis at responding sites was more decreased than non-responding sites after SRP (P<0.05).

CONCLUSIONSRP produced a good clinical improvement. The prevalence and level of P. gingivalis were significantly reduced after SRP. The effect of SRP may be determined by the degree of P. gingivalis is decreased. The real-time polymerase chain reaction can be used to evaluate the effect of periodontal therapy.

Adult ; Dental Plaque ; Dental Plaque Index ; Dental Scaling ; Female ; Humans ; Male ; Middle Aged ; Periodontal Attachment Loss ; Periodontal Pocket ; Periodontitis ; Porphyromonas gingivalis ; Root Planing