Colon ; pathology ; Colonic Polyps ; pathology ; Diagnosis, Differential ; Female ; Humans ; Intestinal Mucosa ; pathology ; Male ; Middle Aged

Objective To observe the clinical efficacy of electroacupuncture plus moxibustion in treating infantile cerebral palsy. Method Eighty eligible patients with infantile cerebral palsy were randomized into a treatment group of 42 cases and a control group of 38 cases. The control group was intervened by physiotherapy (PT), while the treatment group was given electroacupuncture at scalp acupoints, body acupuncture, and moxibustion along the Governor Vessel in addition to the treatment given to the control group. The two groups were treated once a day, 6 months in total. The comprehensive ability and the Gross Motor Function Measure (GMFM) were evaluated before and after the interventions in the two groups, and the clinical efficacies were compared.Result After 6-month treatment, the total effective rate was 92.9% in the treatment group versus 78.9% in the control group, and the total effective rate of the treatment group was superior to that of the control group (P<0.05). The motor function and activities of daily living were significantly improved in both groups after the interventions (P<0.05,P<0.01); after the treatment, there were significant differences in comparing the motor function and activities of daily living between the two groups (P<0.05). The GMFM scores of each domain were significantly changed after the treatment in both groups (P<0.05); after the treatment, there were significant differences in comparing the GMFM scores of each domain between the two groups (P<0.05).Conclusion Compared with being used alone, conventional PT can more significantly benefit the improvement of motor function of cerebral palsy patients when electroacupuncture and moxibustion were added.

BACKGROUND:Bone marrow mesenchymal stem cel transplantation is considered as a promising therapy for spinal cord injury. How to more effectively promote the survival of bone marrow mesenchymal stem cel s in the area of spinal cord injury and to accelerate the recovery of motor function after spinal cord injury is a current study focus. Previous studies have found that low-frequency electromagnetic fields can promote bone marrow mesenchymal stem cel proliferation and differentiation, but whether the low-frequency electromagnetic fields can be applied to bone marrow mesenchymal stem cel transplantation for treatment of spinal cord injury requires further studies. OBJECTIVE:To discuss the effects of low-frequency electromagnetic fields on motor function of spinal cord injury rats after transplantation of bone mesenchymal stem cel s. METHODS:Sixty-four rat models of incomplete spinal cord injury at T 10 were established by compression method and then randomized into control group, transplantation group (bone mesenchymal stem cel transplantation), electromagnetic field group and combination group (electromagnetic field+bone mesenchymal stem cel transplantation). After successful modeling, bone mesenchymal stem cel s labeled with 5-bromo-2'-deoxyuridine were injected into the original injured site in the transplantation group and combination group, which were isolated and purified with the fast adherence method;while alpha-minimum essential medium was injected into the electromagnetic field group and control group for instead. At 24 hours post-operation, the electromagnetic field group and combination group were explored to low-frequency electromagnetic fields (frequency 50 Hz, magnetic indaction intensity 5 mT) for 60 minutes per day. RESULTS AND CONCLUSION:After cel transplantation for 21 days, the Basso, Beattie, and Bresnahan scores in the combination group was higher than the other groups (P<0.05). 5-Bromo-2'-deoxyuridine positive cel s grew wel , and integrated into the normal spine;syringomyelia was reduced, and the number of spinal neural cel s was increased in the combination group. In addition, glial fibril ary acidic protein expression was decreased in the combination group, while matrix metal oproteinase 2 expression was increased. It indicates that low-frequency electromagnetic fields could promote recovery of motor function in the spinal cord injury rats transplanted with bone mesenchymal stem cel s, which could be associated that low-frequency electromagnetic fields facilitate the survival of transplanted bone mesenchymal stem cel s, up-regulate the expression of matrix metal oproteinase 2, and reduce glial scar formation in the spinal cord injured site.

Aim To test the skin healing and repairing efficacy and the mechanism of Hibiscus rosa-sinensis L bud extract by using the animal models. Methods KM mice were randomly divided into three groups:the model group, the positive control group, and the n-bu-tyl alcohol extract ( HrBN) group. Using the boils and carbuncles model, the healing condition of all the animals were observed. KM mice were kept in the SPF condition room and divided into five groups: the model group, the positive control group, and the low, middle, high dose groups. Using the full-thickness loss model, the repairing results of all the mice were ob-served. Through the antimicrobial test, the results of MIC and inhibition zone were obtained. The carbon clearance test was used to collect the blood at the time 5min and 15min, and get the liver and spleen, and the results of K andαwere obtained. Results In vivo ex-periments showed there was significant difference be-tween groups;the HrBN extract had the outstanding ef-ficacy in healing and repairing skin boils and full-thickness loss models. It had higher recovery rate than other ethanol extract, such as ethyl acetate extract and chloroform extract. In vitro experiments showed that the HrBN extract, ethyl acetate extract ( HrBE) ,AB-8 macroporous resin 30% alcohol part and 60% alcohol part had obvious antimicrobial efficacy. The carbon clearance test showed HrBN had a good effect in im-proving immune function, and it can increase the K and α. Conclusion HrBN in animal models exerts good skin healing and repairing efficacy, which might be related to its antibacterial activity and immunologic enhancement function.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

BACKGROUND:The repair and management of ful-thickness skin defects resulting from burns and chronic wounds remain a significant unmet clinical chal enge. Using epidermal stem cel s and keratinocyte growth factor for ful-thickness wound repair is a promising approach. Low-frequency electromagnetic fields which are a non-invasive physical stimulation therapy have been recognized as a good method to enhance wound healing. OBJECTIVE:To develop a new strategy to accelerate wound healing by transplanting transfected epidermal stem cel s and keratinocyte growth factor and treating with low-frequency electromagnetic fields in a mouse model. METHODS:Epidermal stem cel s from Sprague-Dawley neonatal rats were isolated and cultured in vitro, then the cel s were labeled with 5-bromo-2-deoxyuridine and transfected by Ad-KGF, a recombinant adenovirus carrying the keratinocyte growth factor. Mice were given to create ful thickness skin wound on the dorsum and randomly assigned to four groups:control group, transplantation of epidermal stem cel s group, transplantation of keratinocyte growth factor gene modified epidermal stem cel s group, and transplantation of keratinocyte growth factor gene modified epidermal stem cel s plus low-frequency electromagnetic field exposure group. RESULTS AND CONCLUSION:The best healing pattern was observed in the keratinocyte growth factor gene modified epidermal stem cel s plus low-frequency electromagnetic field exposure group (P<0.05) at days 9 and 16. 5-Bromo-2-deoxyuridine labeled cel s existed in the wound in the treated groups at day 9. A significantly increased expression of endogenous keratinocyte growth factor was detected in the transplantation of Keratinocyte Growth Factor gene modified epidermal stem cel s group, and transplantation of keratinocyte growth factor gene modified epidermal stem cel s plus low-frequency electromagnetic field exposure group at day 16. A wel-advanced epithelialization was observed in transplantation of keratinocyte growth factor gene modified epidermal stem cel s plus low-frequency electromagnetic field exposure group at days 16 and 30. These results suggest that low-frequency electromagnetic fields enhanced wound healing fol owing the transplantation of keratinocyte growth factor gene modified epidermal stem cel s.

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Background Drug resistance is the main cause of failure after chemotherapy of retinoblastoma (RB),and how to improve the sensitivity of RB cells to chemotherapic drug become an urgent issue.All trans retinoic acid (ATRA) can inhibit the growth of tumor cells.However,whether ATRA increases the sensitivity of RB cells to chemotherapic drug is unclear.Objective This study aimed to investigate the inhibitory effect of ATRA with vincristine on the proliferation of SO-RB50 cells.Methods SO-RB50 cells were cultured routinely.Different concentrations of ATRA or vincristine were added into the medium for 48 hours for the determination of IC50 by cell counting kit-8 (CCK-8) method.Cultured cells were divided into normal control group,ATRA group,vincristine group and combined drug group.The cells were treated by ATRA or vincristine with the dose of IC50,and the proliferation of the cells was detected every day at the 24-hour interval for 6 consecutive days.The percentage of the cells in different cell cycles was analyzed 72 hours after treatment using flow cytometry.Cell apoptosis rate was detected and calculated 48 hours after treatment by annexin V/propidium iodide (PI) method.Results The IC50 of ATRA was approximately 12.84 μ mol/L,and that of vincristine was 0.11 μg/ml.The growth curve of SO-RB50 cells was gradually raised as the lapse of time,but the curves were relatively low in the ATRA group,vincristine group and combined drug group,with the lowest curve in the combined drug group.The proliferation values of the cells (A450)were 1.078±0.022,0.611 ±0.038,0.596 ±0.031 and 0.483 ±0.030 in 48 hours after treatment,and those in 72 hours were 1.380± 0.021,0.799 ± 0.016,0.668 ± 0.041 and 0.532 ± 0.033 in normal control group,ATRA group,vincristine group and combined drug group,showing significant differences among the groups and various time points (Fgroup =1115.207,P =0.000;Ftime =257.781,P =0.000).The A450 values of the ATRA group,vincristine group and combined drug group were significantly lower than those of normal control group (all at P＜0.05).The percentage of the cells in different cell cycles was changed after 72 hours' treatment and the differences were statistically significant (FG0/G1 =130.565,Fs =57.435;FG2/M =114.290,P＜0.05).Compared with the normal control group,the percentage of G0/G1 phase cells was increased and S phase cells was decreased significantly in ATRA group,the percentage of G0/G1 phase cells was decreased and G2/M phase cells was increased significantly in vincristine group(P＜0.05).The apoptotic rate of the cells was (7.17±0.18) ％,(27.34±1.36) ％,(27.49±2.45) ％ and (34.50±1.84) ％ in normal control group,ATRA group,vincristine group and combined drug group,with a significant difference among the groups (F=147.555,P＜0.05),and the apoptotic rate in the combined drug group was remarkedly lower than that of normal control group,ATRA group and vincristine group (all at P=0.000).Conclusions ATRA can improve the sensitivity of SO-RB50 cells to chemotherapeutic drug.The combined application of ATRA and vincristine enhance the inhibitory effect on the cells probably by regulating cell cycle and inducing apoptosis.