Calcium Channel Blockers ; pharmacology ; Cell Survival ; drug effects ; Drug Antagonism ; Humans ; Kidney ; cytology ; drug effects ; Lead ; toxicity

Animals ; Benchmarking ; methods ; statistics & numerical data ; Dose-Response Relationship, Drug ; Humans ; Models, Statistical ; No-Observed-Adverse-Effect Level ; Risk Assessment ; methods ; statistics & numerical data ; Toxicology ; methods

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

Objective: In order to improve the stability of grape polyphenols and strengthen slow-release effect, the study on micro- capisulazed grape polyphenols was carried out through the complex coacervation method using porous cornstarch as core material carrier. Methods: With the embedding rate as main index, the effect of all factors on the microencapsulation of grape polyphenols was investigated through the single factor test and orthogonal test, and its preparation technology was also optimized. Results: The best preparation technology was as follows: The experiment materials were 10 mL grape polyphenols solution of 25 mg/mL, 1.5 g porous cornstarch, 30 mL sodium alginate solution of 0.03 g/mL, 50 mL chitosan solution of 0.01 g/mL, and 50 mL calcium chloride solution of 0.05 g/mL, at pH value of 3.5. The microcapsules' appearance was superior with size distribution of the main in 600-850 μm, the embedding rate was 83.2%, and they had very good releasing property in simulated gastric and simulated intestinal environment. Conclusion: The product appearance and embedding rate of grape polyphenols microcapsules which used porous cornstarch as core material carrier and sodium alginate-chitosan as wall materials are better than those only used sodium alginate and chitosan as wall materials. Furthermore, the inclusion complex is proved to be successfully prepared by its structural characterization which is gotten from FTIR and scanning electron microscope (SEM).

ObjectiveTo detect specific antigens of neural cells in amniotic epithelial cells(AECs) in rats. MethodsAECs were dissociated and purified from the amnion of pregnancy 12—14 d rats. The expression of specific markers of neural stem cells (Nestin, Musashi) and differentiated cells (MAP-2,NSE,GFAP) and ChAT, NT-3 in the AECs were detected by immunocytochemistry. ResultsThe cultured AECs displayed positive immunoreactivity to MAP-2, NSE, GFAP, Nestin and Musashi. In addition, the cells also demonstrated immunoreactivity to ChAT and NT-3. ConclusionAECs are similar with neural cells and it may be useful as a sustained source to improve outcome of neural stem cells transplantation.

Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
Animals ; Curcumin ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Neuropathies ; drug therapy ; Ganglia, Spinal ; cytology ; drug effects ; metabolism ; Neuralgia ; drug therapy ; Neurons ; drug effects ; metabolism ; Rats ; Sodium ; Voltage-Gated Sodium Channels ; physiology

Objective:This study aimed to investigate the effect of human lymphatic endothelial cells (HLECs) on proteins secreted by epithelial ovarian cancer (EOC) cells SKOV3-pm4 with highly directional lymphatic metastasis. Methods:The supernatants of the four groups of cultured cells (A, SKOV3;B, SKOV3+HLEC;C, SKOV3-PM4;and D, SKOV3-PM4+HLEC) were collected. The proteins of these cells were detected by antibody arrays and iTRAQ-2D-LC-MALDI-TOF/TOF/MS. The screened significantly differential proteins were further analyzed by bioinformatics and validated in the human serum and cell culture medium by ELISA. Results:Progranulin (GRN) and vascular endothelial growth factor A (VEGF-A) were upregulated between groups C and A. In addition, insulin-like growth factor binding protein-7 (IGFBP-7) and secreted protein acid rich in cysteine (SPARC) were downregulated between groups D and C. Comprehensive bioinformatics analysis revealed that IGFBP7 interacted with VEGFA. VEGF exhibited the highest expression in ovarian cancer and IGFBP7 exhibited the lowest expression compared with the serum of the normal control group. Statistically significant differences were observed between the two substances. Conclusion:The HLEC microenvironment is closely associated with directional metastasis in lymph nodes with differential proteins, including matricellular proteins and adhesion factors. In particular, the upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 were closely associated with the directional metastasis of EOC cells in lymph nodes.

OBJECTIVETo compare the difference in the clinical efficacy on posterior circulation ischemia between acupuncture at stellate ganglion and conventional acupuncture as well as the impacts on blood pressure.

METHODSEighty cases of posterior circulation ischemia were randomized into an observation group (40 cases) and a control group (40 cases). In the observation group, acupuncture was applied to the bilateral stellate ganglions on the neck, stimulated with reinforcing technique by rotating the needles. In the control group, the acupuncture of reducing technique was applied to Fengchi (GB 20), Baihui (GV 20), Neiguan (PC 6) and Taichong (LR 3) in the excess syndrome. The even needling or reinforcing technique was applied to Fengchi (GB 20), Baihui (GV 20), Ganshu (BL 18), Shenshu (BL 23) and Zusanli (ST 36) for the deficiency syndrome. The treatment was given once every 3 days and 4 treatments were required totally in the two groups. The changes in total syndrome score, peak Systolic blood flow velocity (Vp) of vertebral artery and basilar artery, systolic and diastolic blood pressures were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups.

RESULTSThe total syndrome score was reduced apparently after treatment compared with that before treatment in the two groups (P < 0.01), and the reducing was more obvious in the observation group as compared with that in the control group (P < 0.01). The total effective rate was 87.5% (35/40) in the observation group, higher than 67.5% (27/40, P < 0.05) in the control group. After treatment, the reduced Vp of vertebral artery was not improved apparently as compared with that before treatment in the control group, Vp in blood velocity abnormality (including vascular spasm, stenosis or reduced velocity) of vertebral artery and basilar artery was all improved as compared with that before treatment in the two groups (P < 0.01), and the improvements in the observation group were more obvious than those in the control group (P < 0.01). After treatment, the systolic and diastolic pressures were reduced as compared with those before treatment in the two groups, and the reduced systolic and diastolic pressures in the observation group were more apparent than those in the control group (P < 0.01).

CONCLUSIONAcupuncture at stellate ganglion achieves the satisfactory efficacy in the treatment of posterior circulation ischemia and the significant efficacy of reducing blood pressure, more advanced than the conventional acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Blood Pressure ; Brain Infarction ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Stellate Ganglion ; physiopathology ; Treatment Outcome

Chronic osteomyelitis is one of the most common disorder in clinic. In recent years due to diabetes, peripheral vascular disease and trauma induced disease increased, the prevalence rate increased. With the development of magnetic resonance imaging and CT imaging technology, it greatly improved the accuracy of clinical diagnosis of chronic osteomyclitis and ability to describe the infection characteristics, and provide a reliable basis for clinical treatment. The current research on chronic osteomyelitis mainly concentrated on the aspects of imaging applications and ways of using antibiotic optimization control inflammation, defect restoration and reconstruction of blood supply and treatment. But the best time to the antibiotic therapy and the use of program is still uncertain, for after debridement, bone grafting time and defect repair function of fast recovery still need further research.
Anti-Bacterial Agents ; therapeutic use ; Chronic Disease ; Humans ; Osteomyelitis ; diagnosis ; therapy

Objective To explore the correlation of bone metabolism levels and risk of coronary heart disease in elder women patients .Methods A total of 163 elder women patients were divided into three group:CON group ,CAD group ,and CHD group .We explored related atherosclerosis risk factors and factors related to bone metabolism .Results Compared with CON group ,there was no statistical significance in CAD group in factors related to bone metabolism(P>0 .05) .In CHD group ,serum 25‐OH‐Vitamin D significantly decreased and β‐C‐terminal telopeptide of type Ⅰ collagen significantly increased compared with CON group(P<0 .05) .Compared with CAD group ,the serum 25‐OH‐Vitamin C also significantly decreased andβ‐C‐terminal telopeptide of type Ⅰcollagen significantly increased(P< 0 .05) .Spearman correlation analysis showed that BMI ,HDL‐C ,triglycerides ,LDL‐C ,blood glucose and 25‐OH‐Vitamin D were correlated with coronary heart disease .With coronary heart disease as the dependent variable , the results showed lower LDL‐C ,25‐OH‐Vitamin D had independent predictive value for the risk coronary heart disease .Conclusion Lower 25‐OH‐Vitamin D levels in elder patients were positively correlated with coronary heart disease ,and it might also be an in‐dependent predictor .