Adult ; Aged ; Aged, 80 and over ; Female ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Humans ; Keratin-18 ; genetics ; metabolism ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; T-Lymphoma Invasion and Metastasis-inducing Protein 1

OBJECTIVETo observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF).

METHODSTotally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis.

RESULTSAfter chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05).

CONCLUSIONT II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up-regulating NGF activities.

Calcitonin Gene-Related Peptide ; blood ; Diterpenes, Abietane ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Nerve Growth Factor ; blood ; Neural Conduction ; drug effects ; Organoplatinum Compounds ; adverse effects ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Up-Regulation

Objective To explore the effect of chromofungin (CHR), a chromogranin A (CGA) derived peptide CGA47-66, on hyper-permeability of blood brain barrier in septic mice. Methods 120 healthy male C57BL/6 mice were randomly divided into groups, with 12 mice in each group. Seventy-two mice were used for dynamic observation of the contents of water and Evan blue (EB) in brain tissue after being treated with lipopolysaccharide (LPS). Another 48 mice were divided into normal saline control group (NS group), LPS induced sepsis model group (LPS group), low-dose CHR pretreatment group (CL+LPS group), and high-dose CHR pretreatment group (CH+LPS group). The septic model was reproduced by intraperitoneal injection of 10 mg/kg LPS 0.1 mL, and the mice in NS group was given equal volume of normal saline. The mice in CL+LPS group and CH+LPS group were intraperitoneally injected with 15.5 μg/kg and 77.5 μg/kg CHR 10 minutes before LPS injection. Six hours after LPS injection, 4 mL/kg of 2% EB was injected via caudal vein, the contents of water and EB in brain tissue were determined, and EB immune fluorescence in brain tissue was determined to assess the changes in permeability of blood brain barrier. Brain pathology was observed with hematoxylin and eosin (HE) staining. Results With the extension of time after LPS injection, the contents of water and EB in brain tissue were gradually increased, and the time of difference with statistical significance appeared earlier when compared with that of control group in the contents of water than that in EB contents (3 hours and 6 hours, respectively). The contents of water and EB in brain tissue in LPS group were significantly increased as compared with NS group [water content: (79.77±0.62)% vs. (78.28±0.44)%, P < 0.01; EB content (μg/g): 13.87±4.50 vs. 7.13±1.76, P < 0.05]. CHR pretreatment with either of two dosages could reverse the increase in water and EB contents in brain tissue induced by LPS, and the effect was more significant in CH+LPS group [water content: (78.15±0.73)% vs. (79.77±0.62)%, EB (μg/g): 7.09±2.59 vs. 13.87±4.50, both P < 0.05]. It was shown by EB fluorescence observation that the fluorescence signal displayed only in the meninges in NS group, and EB fluorescence was widely distributed in brain parenchyma in LPS group, indicating that the EB leakage in LPS group was more marked than that of NS group. In CHR pretreatment groups, EB fluorescence was decreased in brain parenchyma, indicating that EB leakage was significantly less marked, while it was more obvious in high dose CHR group. It was shown by HE staining that cerebral blood vessel structure was intact in NS group, and the gap around blood vessel was not significant increased. On the other hand, brain structure in LPS group appeared loose, with widening of small perivascular spaces and obvious edema. Brain edema in CHR pretreatment groups was improved as compared with that of the LPS group, and it was more apparent in high dose CHR group. Conclusions LPS induced change in blood brain barrier permeability in mice in a time-dependent manner. Exogenous CGA derived peptides CHR can inhibit LPS induced hyper-permeability of blood brain barrier in septic mice, thus reduces brain edema, protects the brain tissue, and the effect is more obvious with a high dose of CHR (77.5 μg/kg).

Objective To evaluate the efficacy of Qingpeng ointment for the treatment of asteatotic eczema and its effect on skin barrier function.Methods A self-controlled clinical study was performed.Totally,78 patients with asteatotic eczema symmetrically located on both lower extremities were enrolled into this study.The left and right lower extremities of these patients were treated with Qingpeng ointment (Qingpeng group) and hydrocortisone butyrate ointment (hydrocortisone butyrate group) respectively,twice a day for 4 consecutive weeks.At the end of treatment,therapeutic effect and skin barrier function were compared between the 2 groups.Results The response rate was significantly higher in the hydrocortisone butyrate group than in the Qingpeng group after 1-and 2-week treatment (week 1:58.97％ vs.39.74％,x2 =5.77,P ＜ 0.05;week 2:76.92％ vs.60.26％,x2 =5.03,P ＜ 0.05),but insignificantly different between the 2groups after 4-week treatment (80.77％ vs.87.18％,P ＞ 0.05).Compared with the hydrocortisone butyrate group,theQingpeng group showed significantly increased water content of the stratum corneum after 4-week treatment (P ＜ 0.05),and decreased transepidermal water loss after 2-and 4-week treatment (both P ＜ 0.05).Conclusion Qingpeng ointment is safe and effective for the treatment of asteatotic eczema with gradually increasing and stable effects,and also has a favoring effect on the restoration of skin barrier function.

Oncomelania hupensis is the only intermediate host of Schistosoma japonicum. The elimination of Oncomelania snails is the key technique step for schistosomiasis control. This paper summarizes the progress of the techniques of snail control，including the methods of ecology engineering，biology，molluscicides and the study on novel molluscicides，and reviews their features. In addition，this paper explores the appropriate approach to control the snails.

BACKGROUND:Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H2O2-induced apoptosis of H9c2 ventricular cells in rats. But the protective effect and mechanism of activating RXR in cardiomyocytes against hypoxia/reoxygenation (H/R)-induced oxidative iniury are stillunclear. METHODS:The model of H/R injury was established through hypoxia for 2 hours and reoxygenation for 4 hours in H9c2 cardiomyocytes of rats. 9-cis-retinoic acid (9-cis RA) was obtained as an RXR agonist, and HX531 as an RXR antagonist. Cultured cardiomyocytes were randomly divided into four groups:sham group, H/R group, H/R+9-cis RA -pretreated group (100 nmol/L 9-cis RA), and H/R+9-cis RA+HX531-pretreated group (2.5 μmol/L HX531). The cellviability was measured by MTT, apoptosis rate of cardiomyocytes by flow cytometry analysis, and mitochondrial membrane potential (ΔΨm) by JC-1 fluorescent probe, and protein expressions of Bcl-2, Bax and cleaved caspase-9 with Western blotting. Allmeasurement data were expressed as mean±standard deviation, and analyzed using one-way ANOVA and the Dunnett test. Differences were considered significant whenP was <0.05. RESULTS:Pretreatment with RXR agonist enhanced cellviability, reduced apoptosis ratio, and stabled ΔΨm. Dot blotting experiments showed that under H/R stress conditions, Bcl-2 protein level decreased, while Bax and cleaved caspase-9 were increased. 9-cis RA administration before H/R stress prevented these effects, but the protective effects of activating RXR on cardiomyocytes against H/R induced oxidative injury were abolished when pretreated with RXR pan-antagonist HX531. CONCLUSION:The activation of RXR has protective effects against H/R injury in H9c2 cardiomyocytes of rats through attenuating signaling pathway of mitochondria apoptosis.

OBJECTIVETo observe application value of multispectral animal living imaging technology in rats model of osteoarthritis.

METHODSFifteen male SD rats weighed (180 +/- 20) g (3 months old) were received intra-articular injection of iodoacetic acid for establishing osteoarthritis. Articular cavity of left knee of rats were injected into 50 microl iodoacetic acid. The same volume of sterile saline was injected into right knee articular cavity as control. X-ray living imaging and bone mineral density were observed at 2 and 4 weeks after establishment of model. After 4 weeks,rats were sacrificed and their bilateral joints were collected and determined histologically based on Collins classification and Kellgren-Lawrence classification.

RESULTSOsteoarthritis model was successfully established, compared with control group, model group showed typical manifestation of osteoarthritis, including irregular cartilage surface,osteophyte formation,joint deformity and cartilage defect,and combined with significant decrease of bone density (P < 0.01), while the decrease was not obvious in proximal tibia (P < 0.05). After 2 weeks, knee joints in model group was classified as Collins grade 1 and Kellgren-Lawrence grade 2,then classified as Collins grade 4 and Kellgren-Lawrence grade 3 after 4 weeks,control group showed smooth articular surface,normal joint space and intact cartilage surface, knee joints was classified as Collins and Kellgren-Lawrence grade 0, and bone density of distal femur and proximal tibia were normal.

CONCLUSIONMultispectral animal living imaging technology could be used in dynamic observation of living imaging and detection of bone density in the animal model of osteoarthritis, and it is significant for evaluation of osteoarthritis model, and its realted tesearch.

Animals ; Bone Density ; Disease Models, Animal ; Humans ; Knee Joint ; diagnostic imaging ; Male ; Osteoarthritis ; diagnosis ; diagnostic imaging ; physiopathology ; Radiography ; Rats ; Rats, Sprague-Dawley

This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.
Biological Transport ; Caco-2 Cells ; Caveolae ; Chitosan ; chemistry ; Clathrin ; Endocytosis ; Humans ; Integrin alphaVbeta3 ; chemistry ; Nanoparticles ; Particle Size ; Pinocytosis

This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.

OBJECTIVETo research the change of concentration of the amino acid neurotransmitters in the striatum focal cerebral ischemia in rat and the effect of Acorus tatarinowii Schott, one of inducing resuscitation drugs, for 4 of amino acid neurotransmitters.

METHODSTwenty four rats were divided into four groups (n = 6): control group, cerebral ischemia group, sham operation group and Acorns tatarinowii Schott treated group. Rats were established into models of cerebral ischemia by occluding bilateral thread cork method. Formation sampling were performed in a striatum area using microdialysis and the detection of biological sample including aspartic acid, glutamic acid, glycine and gamma-aminobutyric acid by high performance liquid chromatography (HPLC) electrochemical detector system.

RESULTSCompared with the control, the all contents of 4 kinds of the amino acids were significantly increased during cerebral ischemia (P < 0.01). Compared with the cerebral ischemia group, the contents of aspartic acid, glutamic acid that were excitatory amino acids were remarkably decreased in the striatum for Acorus tatarinowii Schott treated group (P < 0.01), It was no significant influence on gamma-aminobutyric acid and glycine that belonged to inhibitory amino acid in a nascent condition but with a elevating in the later period of microdialysis.

CONCLUSIONAcorus tatarinowii Schott can enter the cerebral parenchyma through blood brain barrier and cut down glutamic acid,aspartic acid increased during cerebral ischemia. As a result, the neurotoxicity attributed to the excitatory amino acid has been released in excessive amounts declined so as to avoid the secondary impairment of neurons caused by excitatory amino acids pernicious effects after ischemia. It may be one of the protective mechanism of drugs for inducing resuscitation resembling EAA receptor antagonists to ischemi brain.

Acorus ; chemistry ; Animals ; Brain Ischemia ; metabolism ; Corpus Striatum ; metabolism ; Disease Models, Animal ; Excitatory Amino Acids ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley