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

cDNA for Insulin-like growth factor binding protein 3 was cloned and constructed a prokaryotic expression vector--pET-DsBA-IGFBP3. The construct was transformed into E. coli BL21 (DE3)plysS. The induced fusion protein (D-IGFBP3) was expressed successfully in soluble form. We obtained D-IGFBP3 the purify of which is over 95% after purification by His affinity chromatography. The product was identified by Western-blot. The cell assay showed that the obtained fusion protein can inhibit the growth of MCF-7 and bind with IGF-I in vitro.
Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, Affinity ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Gene Expression ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; Protein Binding ; Recombinant Proteins ; isolation & purification ; metabolism ; pharmacology ; Solubility

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, is characterized by allodynia, hyperalgesia and spontaneous pain. Chinese epidemiological studies have shown that at least 25% diabetic patients suffered from painful DPN, which compromises patients' daily functioning and becomes a major health care problem. Although the pathogenesis of painful DPN is not fully understood and current treatment options are very limited, research in the field has advanced our understanding on the mechanism of painful DPN in the past Decade of Pain Research and Control. This review will mainly focus on evaluation of current diabetic animal models, possible molecular pathways and available therapies, with an emphasis on roles of purinergic receptor and its signaling transduction pathways. Common therapies address one or two DPN symptoms, while others offer wider symptom control, presumably by targeting pathophysiological mechanisms of DPN. Purinergic receptor signaling transduction pathways might become potential targets for treatment for painful DPN.
Animals ; Diabetes Mellitus ; physiopathology ; Diabetic Neuropathies ; physiopathology ; Humans ; Hyperalgesia ; physiopathology ; Pain ; physiopathology ; Receptors, Purinergic P2X ; physiology

Adolescent ; Adult ; Antigens, Nuclear ; metabolism ; Brain Diseases ; complications ; diagnosis ; pathology ; surgery ; Brain Neoplasms ; pathology ; Child ; Child, Preschool ; Diagnosis, Differential ; Epilepsy ; etiology ; Female ; Ganglioglioma ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Malformations of Cortical Development ; classification ; complications ; diagnosis ; pathology ; surgery ; Malformations of Cortical Development, Group I ; Microtubule-Associated Proteins ; metabolism ; Neoplasms, Neuroepithelial ; pathology ; Nerve Tissue Proteins ; metabolism ; Neurofilament Proteins ; metabolism ; Retrospective Studies ; Vimentin ; metabolism ; Young Adult

OBJECTIVETo explore the protective mechanism of Nervilia fordii (NF) by observing the effect of its pretreatment on lung aquaporin 1 and 5 (AQP-1, AQP-5) expression in rats with endotoxin-induced acute lung injury (ALI).

METHODSTwenty-four SD rats were randomly divided into 3 groups, the normal group (A), the NF pre-intervention group (B) and the endotoxin model group (C). Rats in Group B and C were made into ALI by endotoxin (5 mg/kg) injection via sublingual vein, and NF pretreatment was applied to Group B. Animals were sacrificed at the 8 h after modeling, their lung were taken for observing the water permeability change by wet/dry weight ratio (W/D) measuring, pathological feature by HE staining, and the expression of AQP-1, AQP-5 was detected by immunohistochemistry and RT-PCR.

RESULTSThe W/D ratio of lung was higher in model rats than in normal rats, but as compared with Group C, it was significantly lower (P < 0.05) in Group B. The pulmonary edematous change was significantly mild and the AQP-1 and AQP-5 protein expressions were significantly higher in Group B than in Group C (P < 0.05).

CONCLUSIONNF pretreatment can promote lung AQP-1 and AQP-5 expression up-regulation, increase lung water clearance and transportation to improve the water balance and eliminate pulmonary edema, so as to effectively protect lung from acute injury.

Acute Lung Injury ; chemically induced ; drug therapy ; prevention & control ; Animals ; Aquaporin 1 ; metabolism ; Aquaporin 5 ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Endotoxins ; Female ; Lung ; metabolism ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Up-Regulation

Glutathione is a tripeptide comprised by L-glutamate, L-cysteine, and glycine, that serves antioxygenation and deintoxication functions within the cell. Recent study has found that glutathione is the main driving force for bile salt-independent bile flow, impaired biliary excretion of glutathione can lead to cholestasis. This review focuses on hepatobiliary transport of glutathione and its role in cholestasis. Based on the evidence of choleretic effect of glutathione, enhancement of biliary excretion of glutathione may be a good strategy for prevention and treatment of cholestasis.
Animals ; Biological Transport ; Cholestasis ; chemically induced ; metabolism ; prevention & control ; Estrogens ; adverse effects ; Glutathione ; metabolism ; Humans ; Jaundice, Chronic Idiopathic ; genetics ; Liver ; metabolism ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Mutation ; Phalloidine ; adverse effects ; Ursodeoxycholic Acid ; therapeutic use

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.
Abdominal Pain ; Action Potentials ; Adult ; Animals ; Architectural Accessibility ; Blotting, Western ; Citric Acid ; Colon* ; Diagnosis-Related Groups ; Female ; Ganglia, Spinal ; Humans ; Hypersensitivity* ; Injections, Intraperitoneal ; Membrane Potentials ; Neurons ; Rats* ; Sensory Receptor Cells* ; Sodium ; Sodium Channels ; Streptozocin ; Up-Regulation ; Voltage-Gated Sodium Channels*

Acetabulum/surgery* ; Arthroplasty, Replacement, Hip/adverse effects* ; Femur Head Necrosis/surgery* ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Hip Fractures/surgery* ; Humans ; Ossification, Heterotopic/surgery* ; Treatment Outcome

Objective To investigate the clinical effect of total hip replacement(THA)in the treatment of traumatic arthritis secondary to acetabular fracture.Methods From October 2019 to June 2022,15 patients with secondary traumatic arthritis of acetabulum fracture were treated with THA.There were 8 males and 7 females,aged from 40 to 76 years old with an average of(59.20±9.46)years old.Prosthesis loosening,dislocation of hip joint,range of motion of hip joint,nerve injury and other conditions were recorded before and after surgery.Harris score,visual analogue scale(VAS)and imaging were used to e-valuate hip joint function and surgical effect.Results Follow-up time ranged 6 to 39 months with an average of(18.33±9.27)months.All the 15 patients successfully completed the operation,no nerve and blood vessel injury during the operation,post-operative wound healing was stage Ⅰ,no infection,one case of acetabular side prosthesis loosening at half a year after opera-tion,and recovered well after revision surgery,one case of hip dislocation was cured after open reduction treatment,no adverse consequences.Harris score at the last postoperative follow-up was(88.60±4.01)points,compared with the preoperative(47.20±1 1.77)points,the difference was statistically significant(P＜0.05),and VAS at the lateat postoperative follow-up was 1(1)points,compared with the preoperative 8(2)points,the difference was statistically significant(P＜0.05).At the last follow-up,the pain symptoms were relieved or disappeared,and the joint function was satisfactory.The imaging data of the latest fol-low-up showed joint was well pseudoradiated,no abnormal ossification occurred,and the prosthesis was not loose.Conclusion THA is effective in the treatment of traumatic arthritis secondary to acetabular fracture and can effectively improve the quality of life of patients.Preoperative comprehensive evaluation and bone defect evaluation of patients,and intraoperative manage-ment of acetabulum,femur,internal fixation and bone defect are key factors for the success of surgery.