Administration, Oral ; Adult ; Drug-Related Side Effects and Adverse Reactions ; nursing ; Female ; Humans ; Potassium Permanganate ; administration & dosage ; poisoning ; Powders

Autophagy is an active research area in the biomedical field as its role has been identified in many physiological and pathological processes. Accordingly, there is a growing demand to identify, quantify and manipulate the process accurately. Meanwhile, there is great interest in identifying compounds that modulate autophagy because they may have applications in the treatment of a variety of autophagy-related diseases. In this review, we summarize the current status of autophagy screening systems to facilitate identification of autophagy modulators.
Autophagy ; Humans

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Due to its effect of systems regulation and promotion on body, Ginseng is always referred to be long-term used as a dietary supplement. But it was still unclear about its target of the tonic effects and also the side-effects long-term use may bring. Urine metabolomic method is suitable for long-term studies of pharmaco-dynamics, pharmacology and toxicology of traditional Chinese medicine because of its characteristics of non-invasive and monitoring the whole-body metabolism. This study was designed to detect the dynamic variation of rat urine metabolome along with a long-term administration of total ginsenosides using GC-TOF based metabolomic technology. Our result showed that either short-term or chronic administration of ginsenosides did not impact the rat urine metabolome significantly (as the PCA subgroup was not successful). By comparison, the short-term (1-3 w) dose of ginsenosides had the biggest metabolic influence including TCA cycle, catecholamines and neurotransmitter amino acids. Medium-term (6-10 w) dose had a gradually lower effect and long-term (27 w) dose almost had no effect. Our study indicates that both short and long-term administration of ginsenosides showed almost no obvious side-effect on the experimental animals.
Animals ; Drugs, Chinese Herbal ; metabolism ; Ginsenosides ; metabolism ; urine ; Male ; Metabolomics ; Panax ; metabolism ; Rats ; Rats, Wistar ; Time Factors

Benzene ; analysis ; Chemical Industry ; Chromatography, Gas ; methods ; Humans ; Occupational Exposure ; analysis ; Toluene ; analysis ; Trichloroethylene ; analysis ; Xylenes ; analysis

Objective: To compare the efficacy difference between moxibustion at sensitized-acupoints and non-sensitized- acupoints using the same group of acupoints. Methods: A total of 139 patients with chronic superficial gastritis were divided into a sensitized acupoint group (102 cases) and a non-sensitized acupoint group (37 cases) based on whether acupoint sensitization occurred. The SPSS version 19.0 statistical software propensity score matching function was used to balance the baseline data between the groups. Finally, 29 pairs of matched patients were included, namely 29 cases in the sensitized acupoint group and 29 cases in the non-sensitized acupoint group. Both groups were treated with moxibustion therapy. The treatment lasted for 30 min per time, and was performed every other day for 8 weeks. Changes in the traditional Chinese medicine (TCM) symptom score and the short-form 36-item health survey (SF-36) score in both groups were observed before and after treatment, as well as the clinical efficacy. Results: The covariates of age, course of disease, TCM symptom score and SF-36 score in the two groups were balanced after matching (all P>0.05). After treatment, the total effective rate was 100.0％ in the sensitized acupoint group and 79.3％ in the non-sensitized acupoint group. The difference in the total effective rate between the two groups was statistically significant (P<0.01). After treatment and at the 4-week follow-up, the TCM symptom scores in the sensitized acupoint group were significantly lower than those in the non-sensitized acupoint group (all P<0.01); the SF-36 scores in the sensitized acupoint group were significantly higher than those in the non-sensitized acupoint group (all P<0.01). Conclusion: With the same group of acupoints, the sensitized acupoints have a better therapeutic effect and long-term efficacy than the non-sensitized acupoints in the treatment of chronic superficial gastritis.

We investigated the development of an injectable, biodegradable hydrogel composite of poly(trimethylene carbonate)-F127-poly(trimethylene carbonate)(PTMC11-F127-PTMC11 )loaded with bone morphogenetic protein-2 (BMP-2) derived peptide P24 for ectopic bone formation in vivo and evaluated its release kinetics in vitro. Then we evaluated P24 peptide release kinetics from different concentration of PTMC11-F127-PTMC11 hydrogel in vitro using bicinchoninic acid (BCA)assay. P24/ PTMC11-F127-PTMC11 hydrogel was implanted into each rat's erector muscle of spine and ectopic bone formation of the implanted gel in vivo was detected by hematoxylin and eosin stain (HE). PTMC11-F127-PTMC11 hydrogel with concentration more than 20 percent showed sustained slow release for one month after the initial burst release. Bone trabeculae surround the P24/ PTMC11-F127-PTMC11 hydrogel was shown at the end of six weeks by hematoxylin and eosin stain. These results indicated that encapsulated bone morphogenetic protein (BMP-2) derived peptide P24 remained viable in vivo, thus suggesting the potential of PTMC11-F127-PT- MC11 composite hydrogels as part of a novel strategy for localized delivery of bioactive molecules.
Animals ; Biocompatible Materials ; chemistry ; Bone Morphogenetic Proteins ; pharmacology ; Bone and Bones ; drug effects ; Dioxanes ; chemistry ; Drug Delivery Systems ; Hydrogels ; chemistry ; Osteogenesis ; drug effects ; Peptides ; Prostheses and Implants ; Rats

OBJECTIVETo investigate the estrogenic activity of icariin and genistein with estrogen-dependent human breast cancer (MCF-7) cells.

METHODMCF-7 cells were incubated with media containing 5% charcoal dextran-treated FBS in phenol red-free media for 48 h. CCK-8 kit was used to study the impact of defferent concentration of icariin and genistein on MCF-7 proliferation in vitro. Optimal concentration icariin and genistein were added into medium and total RNA was isolated after 12, 24, 36, 48 h. The gene expression of ERalpha, ERbeta, PS2, and PR were investigated by Real-time RT-PCR Total protein was also isolated and secretion of ERalpha, ERbeta, PS2, and PR were examined by Western blot.

RESULT10 micromol x L(-1) icariin and genistein could promote the proliferation of MCF-7 evidently. However, the ability of genistein to promote the proliferation was better than icariin. With the concentration of 10 micromol x L(-1), genistein group had a stronger expression of ERa, PS2 and PR mRNA levels than icariin while ERbetaexpression had no significant difference in two group. The same effects were detected by western blotting.

CONCLUSIONBoth genistein and icariin have a strong estrogen-like effect, but the estrogenic activity of genistein is stronger than icariin. It showed that the activity of icariin is stron-ger than genistein to promote ROB maturation. So it must be that icariin promotes the maturation of osteoblasts in vitro by a estogen-independent mechanism.

Cell Proliferation ; drug effects ; Estrogen Receptor alpha ; genetics ; metabolism ; Estrogen Receptor beta ; genetics ; metabolism ; Estrogens ; pharmacology ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Genistein ; pharmacology ; Humans ; MCF-7 Cells ; Osteoblasts ; cytology ; drug effects ; metabolism ; Presenilin-2 ; metabolism

Objective To investigate the efficacy of double-“ U” embedding and pursestring suture and binding pancreaticojejunostomy for the prevention of pancreatic fistula.Methods The retrospective cohort study was adopted.The clinical data of 208 patients who underwent pancreaticojejunostomy at the Hunan Provincial People's Hospital from March 2011 to March 2015 were collected.Of 208 patients,106 patients undergoing double-“ U” embedding and pursestring suture and binding pancreaticojejunostomy were allocated into the double-“ U” group and 102 patients undergoing Child pancreaticojejunostomy were allocated into the Child group.Observation indicators included (1) surgical effects:anastomosis time,postoperative pancreatic leakage,duration of hospital stay,(2) follow-up situations.The follow-up using telephone interview and outpatient examination was performed to detect postoperative long-term complications and recovery of patients by abdominal ultrasound or computed tomography (CT) at every 6 months postoperatively up to September 2015.Measurement data with normal distribution were represented as x ± s and comparison between groups was analyzed by t test.Count data were analyzed using the chi-square test.Results (1) Surgical effects:208 patients underwent successful surgery without occurrence of death.The anastomosis time was (13.0 ± 1.5) minutes in the double-“ U” group and (20.0 ± 1.6) minutes in the Child group,with a statistically significant difference between the 2 groups (t =4.713,P ＜ 0.05).Two patients in the double-“ U” group were complicated with grade A of pancreatic leakage,including 1 of 36 patients with normal pancreatic remnant and 1 of 70 patients with fibrotic pancreatic remnant.Nine patients in the Child group were complicated with pancreatic leakage,including 6 in grade A,1 in grade B and 2 in grade C,and there were 6 of 33 patients (4 in grade A,1 in grade B,1 in grade C) with normal pancreatic remnant and 3 of 69 patients (2 in grade A,1 in grade C) with fibrotic pancreatic remnant.There were statistically significant differences in the pancreatic leakage between the 2 groups and among the patients with normal pancreatic remnant in the 2 groups (x2 =2.951,4.994,P ＜ 0.05).The duration of postoperative hospital stay was (13.5 ± 1.2)days in the double-“U” group and (15.7 ± 2.6)days in the Child group,with a statistically significant difference (t =1.011,P ＜ 0.05).No readmission in the 2 groups occurred.(2) Followup situations:91 of 106 patients in the double-“U” group were followed up for 6-54 months with a median time of 30 months.During the follow-up,8 patients were dead,12 patients didn't undergo reoperation due to multiple metastases in the liver,lung and greater omentum,4 and 4 patients were respectively complicated with relapsing pancreatitis and refluxing cholangitis,and other patients had good conditions without the occurrence of diabetes,diarrhea,indigestion and hypopancreatism.Eighty-eight of 102 patients in the Child group were followed up for 6-54 months with a median time of 25 months.During the follow-up,10 patients were dead,11 patients didn't undergo reoperation due to multiple metastases in the liver,lung and greater omentum,6 and 6 patients were respectively complicated with relapsing pancreatitis and refluxing cholangitis,and other patients had good conditions without the occurrence of diabetes,diarrhea,indigestion and hypopancreatism.Conclusion Double“U” embedding and pursestring suture and binding pancreaticojejunostomy for the prevention of pancreatic fistula can reduce the suture time,incidence of pancreatic leakage and duration of postoperative hospital stay,and it is especially suitable for the patients with normal pancreatic remnant.

BACKGROUND: Classic isolation method of bone marrow mesenchymal stem cells (BMSCs) is Percoll density gradient centrifugation. Blood cell component was removed. However, this method is complicated. Preparation density was needed when isolating dog bone marrow. Moreover, centrifugation was frequent, which had a great damage to cells. OBJECTIVE: To establish methods of the isolation, proliferation, culture and osteoinduction of canine BMSCs, and observe the in vitro proliferation and ability to osteoinduction differentiation. METHODS: 10 mL bone marrow was extracted from dog posterior superior iliac spine, heparin anticoagulation, diluted using Hanks juice, treated with 1.077 g/mL Ficoll solution 3 mL, and centrifuged at 2 000 r/min for 20 minutes. Karyocytes were absorbed to form white cloudlike layering interface, and then centrifuged twice using DMEM supplemented with fetal bovine serum, incubated at 12×10~4/cm~2 at 37 ℃ in a 5% CO_2 incubator. Following subculture, cells were incubated in DMEM containing dexamethasone, β-sodium phosphoglycerol and ascorbic acid 2-phosphate. Immunocytochemical staining and immunofluorescence staining were utilized to detect osteocalcin, osteopontin and type Ⅰ collagen expression in osteoblasts. Alkaline phosphatase staining and alizarin red staining were performed. RESULTS AND CONCLUSION: 1.077 g/mL Ficoll density gradient centrifugation was used to isolate karyocytes that were significant compared with Percoll solution. Obtained BMSCs had high purity, good growth and the mean doubling time was 24 hours. Following in vitro osteogenic incubation of dog BMSCs, osteocalcin, osteopontin and type Ⅰ collagen showed positive expression. Alkaline phosphatase staining demonstrated bluish-green cytoplasm. Alizarin red staining showed red nodes in extracellular matrix, and could differentiate into osteoblasts in vitro.