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

OBJECTIVETo evaluate the clinical effects of iliolumbar fixation for the sacrum fractures of Denis type II.

METHODSThe clinical data of 86 patients with sacrum fracture of Denis type II treated by iliolumbar fixation from January 2008 to January 2012 were retrospectively analyzed. There were 55 males and 31 females, aged from 17 to 55 years old with an average of 39.1 years. Among them, 73 cases complicated with pelvis fracture and 13 cases with acetabular fracture; 37 cases with sacral neurological symptoms and 49 cases without sacral neurological symptoms. Fracture healing time, nerve function, clinical function and complications were observed in the patients.

RESULTSIn 86 cases, 6 cases were out of followed-up and 80 cases were followed up from 24 to 71 months with an average of 36 months. The mean fracture healing time was 13 weeks (ranged, 10 to 38 weeks). According to Gibbons scoring to evaluate the neurological function, preoperative nerve rehabilitation, lower limbs feeling, lower limbs activity,bladder and rectum function,total score respectively were 0.62 +/- 0.04, 1.54 +/- 0.35, 1.12 +/- 0.18, 0.23 +/- 0.01, 3.46 +/- 0.47 and postoperative respectively were 0.82 +/- 0.12, 0.36 +/- 0.04, 0.05 +/- 0.01, 0.03 +/- 0.01, 1.25 +/- 0.22, there were statistically significant differences between preoperative and postoperative (P < 0.05). According to Majeed scoring to evaluate the clinical function, postoperative pain, standing, sitting, sexual life, work ability, total score respectively were 22.54 +/- 4.02, 27.93 +/- 5.46, 8.47 +/- 3.61, 2.54 +/- 1.33, 16.46 +/- 4.34, 81.32 +/- 8.73, 60 cases got excellent results, 17 good, 3 fair. The main complications including fracture nonunion of 5 cases,deep incision infection of 1 case, and screw prominence resulting uncomfortable of 8 cases.

CONCLUSIONIliolumbar fixation has the advantages of stable fixation, satisfactory functional rehabilitation, less complications, and is a good method in treating sacrum fracture of Denis type II.

Adolescent ; Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sacrum ; injuries ; surgery ; Spinal Fractures ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the effect of total flavonoids of Herba Epimedium (FHE) on BMP-2/RunX2/OSX signaling pathway in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

METHODSPassage 3 BMSCs were randomly divided into the control group, the experimental group, and the inhibitor group. BMSCs in the control group were cultured in 0.2% dimethyl sulfoxide + Osteogenuxic Supplement (OS) fluid + DMEM/F12 culture media. BMSCs in the experimental group were intervened by 20 microg/mL FHE. BMSCs in the inhibitor group were intervened by 20 microg/mL FHE and 1 microg/mL NOGGIN recombinant protein. At day 9 alkaline phosphatase (ALP) activity was measured. Calcium nodules were stained by alizarin red staining and the density was observed. The transcription expression of osteogenic differentiation-related proteins (type I collagen, osteocalcin, and osteopontin) and related factors of BMP-2/RunX2/OSX signaling pathway was assayed by RT-PCR.

RESULTSCompared with the control group, ALP activities were enhanced and the density of calcium nodules significantly increased; type I collagen, osteocalcin, and osteopontin expression levels were increased in the experimental group. The expression of osteogenesis-related transcription factor was also increased in the experimental group. Noggin recombinant protein inhibited FHE promoting BMSCs osteogenesis in the inhibitor group. Compared with the experimental group, ALP activity decreased (P < 0.05), the density of calcium nodules was lowered, expression levels of type I collagen, osteocalcin, osteopontin significantly decreased (P < 0.05) in the inhibitor group.

CONCLUSION20 microg/mL FHE promoted osteogenic differentiation process of BMSCs by BMP-2/RunX2/OSX signaling pathway.

Bone Morphogenetic Protein 2 ; metabolism ; Cell Differentiation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Flavonoids ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Osteocalcin ; metabolism ; Osteogenesis ; drug effects ; Osteopontin ; metabolism ; Signal Transduction ; Sp7 Transcription Factor ; Transcription Factors ; metabolism

The endophytic microorganisms found widely in many kinds of plants mediate various effects to theirs hosts. In this study, seven different dominant endophytes (SDE01 to 07) isolated from a Hy-peraccumulator-Solanum nigrum L. were resistant to Cd2+, and the strain SDE06 survived even in the medium containing 80 mg/L of Cd2+. Bacteria strain SDE06 was identified as Bacillus sp.. The removal of Cd2+ of SDE06 in different conditions were studied. Under the optimal conditions, the incubating time was 36 h, the solution pH 6.0, the temperature was 37?C and the Cd2+ concentration of medium was 20 mg/L, the highest removal rate was up to 80.2% at this condition.

To study the anti-tumor metastatic constituents in Rhodiola wallichiana (HK) S H Fu var Cholaensis (Praeg) S H Fu, chemical constituents were isolated and purified by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the activities of the isolated compounds. Ten compounds (1-10) were isolated and their structures were identified by comparison of their spectral data with literature as follows: syringic acid (1), salidroside (2), tyrosol (3), scaphopetalone (4), berchemol (5), 2,6-dimethoxyacetophenone (6), rhobupcyanoside A (7), miyaginin (8), chavicol-4-O-β-D-apiofuranosyl-(1 --> 6)-O-β-D-glucopyranoside (9), eugenyol-O-β-D-apiofuranosyl-(1 --> 6)-O-β-D-glucopyranoside (10). Compounds 4-6 and 8-10, were isolated from this genus for the first time, while compound 7 was isolated from this plant for the first time. Compounds 2, 6-8 showed positive anti-tumor metastatic activities, and compounds 2 and 8 showed significant anti-tumor metastatic activities.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Humans ; Neoplasm Metastasis ; prevention & control ; Rhodiola ; chemistry

BACKGROUND: In the treatment of unicompartmental knee osteoarthritis, unicompartmental knee arthroplasty has the advantages of less blood loss, less trauma, quick recovery, maximum retention of bone mass, low cost, fewer complications and higher patient satisfaction. However, for the mobile bearing and the fixed bearing, the choice of single condylar prosthesis is till controversial.OBJECTIVE: To investigate the difference of LINK fixed-bearing and Oxford mobile-bearing unicompartment arthroplasty in relieving knee joint pain, reconstruction of the knee joint function, correct the knee joint deformity for medial unicompartment knee osteoarthritis, thus providing the basis for selecting a better prosthesis.METHODS: Ninety patients with medial unicompartment knee osteoarthritis undergoing unicompartmental knee arthroplasty in the Department of Joint Surgery, Guangdong Provincial Hospital of TCM from December 2014 to June 2016 were analyzed retrospectively, followed by allotted into Oxford mobile-bearing and LINK fixed-bearing groups (n=45 per group). The preoperative and postoperative pain level, range of motion of the knee, complications, and limb alignment were assessed. The range of motion and function of the knee were evaluated by Knee Society Score system.RESULTS AND CONCLUSION: (1) The two kinds of prosthesises both could obtain good clinical effectiveness. (2)There was no significant difference in the Knee Society Score, Visual Analogue Scale scores, or the range of motion of the knee between two groups (P > 0.05). (3) No complications such as deep vein thrombosis, prosthesis loosening and joint revision were found in both groups. (4) The correction of limb alignment showed significant difference between two groups (P < 0.05). The corrective femorotibial angle in the Oxford mobile-bearing group was larger than that in the LINK fixed-bearing group. (5) These findings manifest that under the precondition of strictly mastering the indications, both fixed-bearing and Oxford mobile-bearing unicompartment arthroplasties can effectively relieve the pain and improve the function of knee joint in the treatment of unicompartmental knee osteoarthritis. Oxford mobile-bearing prosthesis exhibits advantage in restoring the limb alignment; the movable platform lower limb alignment correction angle is often bigger than fixed platform correction angle, but may accelerate the lateral cartilage wear.

AIMTo explore the relationship between the effects of curcumin on cerebral ischemic/reperfusion injury and immediately genic expressions of Fos, Jun and NF-kappaB in hippocampal CA1 area.

METHODSGerbils were randomly divided into sham group (SH), ischemia/reperfusion group (I/R), curcumin group (CU) and solvent control group (SC). Forebrain ischemia was induced by occlusion of bilateral common carotid arteries. Observations were carried out in each group 15 min, 1 h, 2 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia: open field test was used to examine the behavioral change, the apoptosis neurons in hippocampal CA1 region was counted, the expression of Fos, Jun and NF-kappaB in hippocampal CA1 was detected by SABC immunocytochemical technique.

RESULTSThe behavioral mark and the number of apoptosis neurons in hippocampal (CA1 region was much less in CU group than in I/R group (P < 0.01) The expression of Fos was more and the expression of Jun and NF-kappaB was less in CA1 area in CU group than in I/R group (P < 0.01).

CONCLUSIONCurcumin can significantly protect neurons against cerebral ischemia, increasing the expression Fos and decreasing the expression of Jun and NF-kappaB may be the protective mechanisms.

Animals ; Apoptosis ; Brain Ischemia ; metabolism ; pathology ; Curcumin ; pharmacology ; Gerbillinae ; Hippocampus ; drug effects ; metabolism ; Male ; NF-kappa B ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Reperfusion Injury ; metabolism ; pathology

OBJECTIVETo investigate the potential effect of bifidobacterial supplement on intestinal mucosal immunity associated with severe burns.

METHODSWistar rats were randomly divided into burn control group (BC group, n = 30), treatment group (BT group, n = 30), and sham-burn group (NC group, n = 10). Rats in BT group were fed bifidobacterial preparation (5 x 10(9) CFU/ml) after 30% total body surface area full-thickness burns, 1.5 ml, twice daily. Rats in BC group and NC group were fed normal saline, 1.5 ml, twice daily. Samples were taken on post-burn 1-, 3-, and 5-day. The incidence of bacterial translocation and bifidobacteria counts in the cecum mucosa were determined with standard methods. The sIgA levels in the mucus of the small intestine were measured by RIA. The positive sIgA expression in the lamina propria was detected by immunohistochemical staining.

RESULTSThe incidence of bacterial translocation was 42% and 16% in BC and BT groups on post-burn day 3 (P = 0.004), 30% and 8% on day 5 (P = 0.002), respectively. Plasma endotoxin levels were markedly higher in BC and BT groups than in NC group at the early stage post-burn. There was a significant decrease between BT group and BC group on post-burn day 1 (P = 0.0412). Bifidobacteria counts in cecum mucosa were reduced by 10- to 60-fold after thermal injury, but there was a remarkable increase in bifidobacteria counts in animals fed with bifidobacteria. sIgA levels in the intestinal mucus were significantly decreased in group BC, but they returned to normal range in BT group on post-burn day 5. Similarly, sIgA expression in the lamina propria was also weakened after burns, and had a tendency to recover after prescription of a 5-day bifidobacteria-supplemented formula. A strong positive correlation was observed between the counts of bifidobacteria in the cecal mucosa and the levels of sIgA in the intestinal mucus (r = 0.7534, P = 0.0000).

CONCLUSIONSThe expression and excretion of sIgA in the intestine appear to be markedly inhibited following a severe thermal injury. The supplement of exogenous bifidobacteria could improve sIgA formation in the small intestine, thereby reducing the incidence of bacterial/endotoxin translocation secondary to major burns.

Animals ; Bacterial Translocation ; Bifidobacterium ; physiology ; Burns ; immunology ; microbiology ; Disease Models, Animal ; Female ; Immunoglobulin A, Secretory ; biosynthesis ; Intestinal Mucosa ; immunology ; microbiology ; Male ; Probiotics ; Random Allocation ; Rats ; Rats, Wistar

AIMTo determine whether serotonin, a major neurotransmitter in brain, can modulate the production of secretory beta-amyloid protein precursor (sAPP) by activation of serotonin 5-HT2C receptor.

METHODSThe hippocampal slices of rats were incubated with various concentrations of serotonin, M-110, or L-107. sAPP released into the incubation medium were assayed by Western blot analysis assay with monoclonal antibody 22C11 for 2 h.

RESULTSVarious concentrations of serotonin (1.0 x 10(-2) - 1.0 x 10(3) micromol x L(-1)), M-110, a serotonin 5-HT2C agonist (1.5 x 10(-6) - 1.5 x 10(3) micromol x L(-1)), showed positive effect on the production of sAPP while L-107, a serotonin 5-HT2C antagonist (1.0 x 10(-9) - 1.0 x 10(3) micromol x L(-1)), showed negative effect on the production of sAPP over controls.

CONCLUSIONSerotonin modulates production of secretory amyloid beta-protein precursor through serotonin 5-HT2C receptor in incubated rat hippocampal slices.

Amyloid beta-Protein Precursor ; secretion ; Animals ; Hippocampus ; metabolism ; In Vitro Techniques ; Male ; Peptide Fragments ; secretion ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2C ; Serotonin ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists

OBJECTIVETo evaluate in vivo gene delivery of Bio-Oss coated with adeno-associated virus-mediated human bone morphogenetic protein 7 (rAAV-BMP7/Bio-Oss) for bone regeneration around dental implants.

METHODSIn vitro rAAV-BMP7 were constructed and compounded with Bio-Oss. In 6 male New Zealand rabbits, two hydroxyapatite (HA) coated titanium dental implants were placed respectively to each animal in the bilateral tibia metaphysis. Before implantation, a standardized gap (8 mm in width, 4 mm in depth) was created between the implant surface and the surrounding bone walls. Rabbits were randomly divided into three groups (group A, B, C). Gaps of group A were filled with rAAV-BMP7/Bio-Oss (n = 4), gaps of group B were filled with Bio-Oss alone (n = 4), and gaps of group C were filled with nothing (n = 4). The rabbits were sacrificed at 4 and 8 weeks respectively, and the sclerous tissue slices obtained, then histology and histomorphometric analysis were conducted.

RESULTSHistological and histomorphometric analysis revealed an enlarged bone-forming area in the bone defects of group A and B at 4 and 8 weeks after implantation. Greater bone-implant contact was achieved with rAAV-BMP7/Bio-Oss than with Bio-Oss alone and this difference was statistically significant (P < 0.05).

CONCLUSIONrAAV-BMP7/Bio-Oss can induce a stronger peri-implant bone reaction and larger new bone formation than Bio-Oss alone in the treatment of bone defects adjacent to titanium dental implants.

Animals ; Bone Morphogenetic Protein 7 ; Bone Regeneration ; Bone Substitutes ; Bone and Bones ; Dental Implantation, Endosseous ; Dental Implants ; Durapatite ; Humans ; Male ; Minerals ; Rabbits ; Titanium