OBJECTIVE: To investigate the brain pharmacokinetics of co-modified liposomes of α-cobrotoxin in rats after intranasal administration. METHODS: DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were synthesized by Michael addition reaction. And their structures were verified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and infrared spectroscopy (FTIR). Pep2(Pep1)-αCT-LP was prepared by the method of thin-film hydration and post-inserting, then its morphology, particle size, and Zeta potential were investigated. The encapsulation efficiency of liposomes was determined by ultrafiltration centrifugal method. The concentrations of αCT-LP, Pep1-αCT-LP, Pep2-αCT-LP, and Pep2(Pep1)-αCT-LP in periaqueductal gray (PAG) after intranasal administration were measured by microdialysis and the pharmacokinetical parameters were analyzed by PKSolver software. RESULTS: The structures of DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were proved by 1H-NMR and FTIR. The prepared Pep2(Pep1)-αCT-LP was nearly spherical with uniform size, the mean particle size was (115.8±1.86) nm, and the Zeta potential was (-13.77±0.75) mV. Besides, the encapsulation efficiency was (32.75±1.12)%. The RESULTS ofin vivo test demonstrated that the αCT concentrations in PAG after intranasal administration of Pep2(Pep1)-αCT-LP were significantly increased compared with the groups of αCT-LP, Pep1-αCT-LP and Pep2-αCT-LP(P<0.05). Theρmax, tmax, and AUC0→∞ were (244.72±3.15) ng·mL-1, (88.01±4.19) min, (89 199.02±1 922.99) ng·min·mL-1, respectively. CONCLUSION: Pep2(Pep1)-αCT-LP can significantly increase the concentrations of αCT in periaqueductal gray, which provides a promising method for development of polypeptide agents for brain-targeting.

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cervical Intraepithelial Neoplasia ; drug therapy ; metabolism ; pathology ; surgery ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; metabolism ; pathology ; surgery ; virology ; Neoplasm Staging ; Neprilysin ; metabolism ; Papillomavirus Infections ; Prednisone ; therapeutic use ; Receptors, Complement 3d ; metabolism ; Rituximab ; Uterine Cervical Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; virology ; Vincristine ; therapeutic use

Purpose To investigate the expression level of MED27 in lung cancer tissue samples and lung cancer cell lines and to further study the biological function of MED27 in lung cancer cells.Methods Immunohistochemistry and Western blot were used to detect MED27 expression in 70 lung cancer tissues and 5 different lung cancer cell lines,and the correlation between MED27 expression and gender,age as well as PTNM was also analyzed.The silence sequence of MED27 was designed by the siRNA technique.Western blot was used to detect the silence efficiency of MED27.The proliferation,migration and invasion ability of cells were assessed by CCK-8 assay,Scratch assay and Transwell assay after the MED27 was knocked down.Western blot was used to detect the expression of protein involved in the cell proliferation,migration and invasion.Results The results of immunohistochemistry and Western blot showed that MED27 expression was higher in lung cancer tissues and cells (P ＜ 0.05).The expression of MED27 was positively correlated with lymph node metastasis (x2 =9.438,P =0.002,P ＜ 0.05).However,it was not related with gender,age,tumor size and distant metastasis (P ＞ 0.05).The knockdown of MED27 by MED27 specific siRNA could inhibit the proliferation,migration and invasion of H460 cells (P ＜ 0.05).The expression of MMP-2 and MMP-9 involved in the cell migration that were significantly inhibited in H460 cells transfected by MED27 siRNA,and the expression of E-cadherin,related with cell invasion was also decreased,while E-cadherin negative regulatory protein Snail was increased.Conclusion MED27 is highly expressed in lung cancer tissues and cells and high expression of MED27 predicts poor prognosis in lung cancer patients.The knockdown of MED27 inhibits the proliferation,migration and invasion ability of lung cancer cells.All of the above results suggest that MED27 is expected to be a candidate target of lung cancer gene therapy.

Stress cardiomyopathy is an atypical myocardial disease induced by emotional or physical stress, with the characteristic of left ventricular systolic dysfunction, transient imaging and electrocardiogram (ECG) changes. Sudden cardiac death can occur in severe cases. Clinical symptoms are likely to appear on acute myocardial infarction, but the exact pathological mechanism is unclear. In the present study, we perform a systematic review of the literature on the clinical manifestations, epidemiological characteristics, ECG, imaging and laboratory tests of stress cardiomyopathy, in order to provide the values for forensic pathology diagnosis.
Death, Sudden, Cardiac ; Diagnostic Imaging ; Electrocardiography ; Humans ; Myocardial Infarction ; Stress, Psychological ; Takotsubo Cardiomyopathy/physiopathology*

OBJECTIVETo investigate the role of autophagy inhibitor chloroquine (CQ) in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in hypoxia conditions.

METHODSThe following groups in this study were set up: control group, hypoxia group, 50 micromol/L CQ + hypoxia group, 50 micromol/L CQ group. The viability of PASMCs in every group was detected by MTT assay. Autophagic vacuoles in the cells were observed by MDC staining. Protein expression of microtubule associated protein light chain 3 (LC3) was measured by Western blot. Migration of PASMCs was detected by wound healing assay.

RESULTSCompared with control group, no effect on the viability of PASMCs was observed treated by CQ alone. In 1% hypoxia group, cell viability increased significantly compared with that in control group. The number of autophagic vacuoles and the rate of cell migration and also protein expression of LC3-II were also markedly increased. Compared with hypoxia group, addition of CQ increased the number of autophagic vacuoles and the levels of LC3-II protein, but decreased the proliferation and migration of PASMCs.

CONCLUSIONHypoxia could activates autophagy and contributes to proliferation and migration of PASMCs, and autophagy inhibitor CQ could decrease the effect of hypoxia on PASMCs through inhibiting autophagy process.

Autophagy ; drug effects ; Cell Hypoxia ; Cell Movement ; Cell Survival ; Cells, Cultured ; Chloroquine ; pharmacology ; Humans ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; Pulmonary Artery ; cytology

Macrophages have two major roles in regulating the dynamic equilibrium in erythropoiesis, promoting the differentiation and maturation of nucleated red blood cells into reticulocytes and removing old red blood cells. A recent mouse study has demonstrated that the phenotype of macrophages in erythroblastic islands is CD169+ VCAM-1+ ER-HR3+ CD11b+ F4/80+ Ly-6G+. Molecular connections between erythroid progenitor cells and central macrophages help to maintain the function and integrity of erythroblastic islands. New research advances in Kruppel-like factor 1 (KLF1) provide new evidence for the important role of macrophages in erythroblastic islands. Macrophages play an important role in erythropoiesis both in sickness and in health, and provide a potential targeted therapy for diseases such as polycythemia vera and beta-thalassemia in the future.
Animals ; Erythropoiesis ; Humans ; Integrin alpha4beta1 ; physiology ; Kruppel-Like Transcription Factors ; physiology ; Macrophages ; physiology ; Mice ; Phenotype ; Vascular Cell Adhesion Molecule-1 ; physiology

To study relevant risk factors of Shenmai injection induced adverse reactions by using Logistic model and ROC curve, and made the prediction for the occurrence of relevant adverse reactions/events. Case data of patients treated with Shenmai injection were collected by using the prospective, multi-center, large-sample, nested-case control method, in order to analyze the risk factors of Shenmai injection-induced adverse reactions/events, establish the logistic model and draw the receiver operating characteristic (ROC) curve for risk factors. During the study, 7632 patients (including 3 477 males and 4 155 females) were included, and eight of them suffered adverse reactions/events. Based on a multi-factor Logistic model analysis, the age (> or = 50 years) (OR = 5.061, 95% CI: 2.197-7.924; P = 0.001), the total number of medication days (OR = -1.020, 95% CI: -l.652 - 0.388; P = 0.002) and the single dose (OR = 0.245, 95% CI: 0.127-0.364; P = 0.000) were significant independent risk factors for Shenmai injection-induced adverse reactions/events. According to the results, ROC curves were drawn with age (> or = 50 years), the total number of days of inedication and single dose; The area under ROC curves the joint predictor (0.9753, 95% CI: 0.9443-1.000, P < 0.005) was larger than that of the other three single indexes, with a higher risk prediction value. The independent risk factors for Shenmai injection-induced adverse reactions/events included the age (> or = 50 years), the total number of days of medication and single dose. In clinical practice, the age (> or = 50 years), the total number of days of medication and the medication dose can be substituted in the joint predictor calculation formula (P = 1 / [1 + e(-(-21.58 + 5.061 x Xage - 1.020 x Xd + 0.245 x X(mL)] to predict the potential adverse reactions of patients and adjust the dosage regimen.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Humans ; Infant ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; ROC Curve ; Risk Factors ; Young Adult

OBJECTIVETo determine the expressions of HO-2 and eNOS in the corpus cavernosum of castrated rats and investigate the correlation of HO-2 and eNOS with erectile dysfunction.

METHODSForty SD rats of 10 weeks were equally divided into 3 castrated groups (4, 8 and 12 weeks respectively after removal of bilateral testes) and a sham operation control group. All the rats were detected for serum testosterone (T), intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) 2, 8 and 12 weeks after the surgery, the content of HO-2 analyzed by Western blot and the expressions of eNOS and HO-2 determined by immunohistochemistry.

RESULTSTestosterone level and ICP/MAP ratio were markedly decreased after the castration (P < 0.05). The HO-2 expression was detected in the corpus cavernosum of all but the 12-week castrated rats, and the area under the curve was (341.50 +/- 99.70) in the 4-week castrated group, significantly less than in the 8-week (705.00 +/- 152. 74) and the control group (876 +/- 443. 36) (P < 0. 05), with no obvious difference between the latter two. eNOS was found mainly in the vascular endothelial cells of the corpus cavernosum, significantly less in the castrated (123.94 +/- 30. 23) than in the control group (421.21 +/- 125. 12).

CONCLUSIONAndrogens might mediate the penile erectile function through HO-2 and eNOS in the corpus cavernosum of rats.

Animals ; Blood Pressure ; Blotting, Western ; Erectile Dysfunction ; blood ; enzymology ; physiopathology ; Heme Oxygenase (Decyclizing) ; metabolism ; Immunohistochemistry ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Orchiectomy ; Penis ; metabolism ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

OBJECTIVETo investigate the expression of Rho-kinase and heme oxygenase and the interaction among NOS/NO, HO/CO and RhoA/Rho-kinase in the corpus cavernosum of spontaneous hypertensive rats (SHRs).

METHODSA series of electric stimuli were applied to the corpus cavernosum nerves of 7 SHRs, the changes of ICP/MAP observed continuously and the expressions of ROCK2, HO-2 and eNOS analyzed by Western blot and immunohistochemistry. Another 7 WKY rats were taken as controls.

RESULTSCompared with the controls, ICP/MAP did not rise obviously (P < 0.05), HO-2 dropped sharply (P = 0.006) and the expression of the ROCK2 protein was elevated markedly (P = 0.017) in the SHRs. Immunohistochemistry showed HO-2 to be distributed in the smooth muscle cells and nervous cells of the corpus cavernosum, and eNOS mainly in the vascular endothelial cells. The expressions of HO-2 and eNOS were obviously reduced in the SHRs.

CONCLUSIONNOS/NO, HO/CO and RhoA/Rho-kinase are related with erectile dysfunction in SHRs and may interact on one another.

Animals ; Blotting, Western ; Erectile Dysfunction ; enzymology ; physiopathology ; Heme Oxygenase (Decyclizing) ; metabolism ; Hypertension ; enzymology ; physiopathology ; Immunohistochemistry ; Male ; Penis ; enzymology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; rho-Associated Kinases ; metabolism

OBJECTIVETo investigate the profile and significance of changes in thyroid function and cortisol in critically ill patients.

METHODSChemiluminescent microparticle immunoassay (CMIA) was used to measure the serum thyroid hormone, thyroid stimulating hormone and cortisol levels in 51 patients at the first day and in the 45 patients still alive at the third day after hospitalized in ICU. In the 45 patients, 17 cases were complicated with multiple organ dysfunction syndrome (MODS) and 28 cases were not. The age, blood glucose levels and APACHE II scores were also recorded at the first day.

RESULTSIn the 45 patients, serum FT(3) decreased in 41 patients (91%), cortisol increased in 33 patients (73%), especially in the first 24 hours. Compared with non-MODS group, serum FT(3), FT(4) and cortisol levels changed significantly in MODS group. Serum FT(4) reduced apparently in 6 dead patients. Serum FT(3) level was negatively correlated with APACHE II, and cortisol level was positively correlated with APACHE II.

CONCLUSIONSThyroid hormone and cortisol were apparently abnormal and correlated with APACHE II score, especially in patients with MODS. Serum FT(4) might serve as an index to judge the prognosis of the patients.

APACHE ; Adult ; Aged ; Aged, 80 and over ; Critical Illness ; Female ; Humans ; Hydrocortisone ; blood ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Thyroid Hormones ; blood ; Time Factors