Communicable Diseases ; genetics ; immunology ; Epstein-Barr Virus Infections ; genetics ; immunology ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; genetics ; Genotype ; HIV Infections ; genetics ; immunology ; Hepatitis B ; genetics ; immunology ; Hepatitis B virus ; genetics ; Humans ; Malaria ; genetics ; immunology ; Polymorphism, Single Nucleotide ; Toll-Like Receptor 9 ; genetics

OBJECTIVE:To investigate the effects of hydrophilic polymers on the stability of self-microemulsifying drug deliv-ery systems (SMEDDS). METHODS:Taking felodipine (FDP) as model drug,the content of FDP was determined by HPLC method. The effects of pure water,0.5% Kollidon VA64,HPMC E5,HPMC K100LV,HPMC K4M,PVP K30 solution,while 0.1%,0.5% and 1.0% HPMC E5 and Kollidon VA64 on residual content of dissolved FDP were determined in SMEDDS. RE-SULTS:The residual contents of dissolved FDP in SMEDDS placed in Kollidon VA64,HPMC E5,HPMC K100LV,PVP K30, HPMC K4M and pure water for 1 h were 92.7%,63.6%,50.2%,46.2%,36.0%and 24.0%,respectively. The order of maintain-ing the supersaturation state was Kollidon VA64>HPMC E5>HPMC K100LV>PVP K30>HPMC K4M>pure water. The residu-al contents of dissolved FDP in SMEDDS placed in 0.1%,0.5%,1% Kollidon VA64 and HPMC E5 and pure water for 1 h were 93.2%,95.1%,96.0% and 48.4%,62.1%,75.1%. CONCLUSIONS:Kollidon VA64 and HPMC E5 can significantly inhibit drug release in SMEDDS and be used as stabilizer of SMEDDS,wherein Kollidon VA64 was better.

Objective To compare the roles of Toll-like receptor 4 (TLR4)/NF-κB signal pathway in acute lung injury (ALl) induced by blunt chest trauma and by blunt chest trauma-hemorrhagic shock and resuscitation (double hits) in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 240-280 g,were randomly assigned into 3 equal groups (n =10 each) using a random number table:sham operation group (S group),blunt chest trauma group (T group),and blunt chest trauma and hemorrhagic shock and resuscitation group (group THSR).Lung contusion was induced in anesthetized rats by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.At 6 h after the model was established,the arterial blood samples were collected for blood gas analysis and detection of tumor necrosis factor-alpha (TNF-α) concentrations in serum.Oxygenation index (PaO2/FiO2) was calculated.The rats were then sacrificed and pulmonary specimens were obtained for determination of TLR4 expression and NF-κB ac tivity (by immunohistochemistry and Western blot) in lung tissues and for microscopic examination.Results Compared with group S,PaO2 and PaO2/FiO2 were significantly decreased,PaCO2 and TNF-α concentrations in serum were increased,TLR4 expression was up-regulated,and NF-κB activity was enhanced in T and THSR groups (P ＜ 0.05).Compared with group T,PaO2 and PaO2/FiO2 were significantly decreased,PaCO2 and TNF-α concentrations in serum were increased,TLR4 expression was up-regulated,and NF-κcB activity was enhanced in THSR group (P ＜ 0.05).The histopathological damage to lung tissues was aggravated in THSR group as compared with T group.Conclusion The role of TLR-4/NF-κB signal pathway in ALI induced by blunt chest traumahemorrhagic shock and resuscitation (double hits) is significantly stronger than that in ALI induced by blunt chest trauma alone in rats.

OBJECTIVETo study the effects of arsenic trioxide (As2O3) on the proliferation and the migration force of human breast cancer SKBR-3 cell and the expression of Notch1.

METHODSSKBR-3 cells were cultured with different concentrations of As2O3 for 24 h and with the final concentration of 8 micromol/L for 24, 48, and 72 h. The effects of As2O3 on the cell proliferation of SKBR-3 were detected by MTT assay. The effects of the migration force of SKBR-3 cells were detected by Transwell. The expression of Notch1 mRNA was detected using reverse transcription polymerase chain reaction (RT-PCR). The expression of Notch1 protein was detected using Western blot.

RESULTSAs2O3 could significantly inhibit the proliferation of SKBR-3 cells in a concentration- and time-dependent manner (P < 0.05). It also could inhibit the migration force of SKBR-3 cells (P < 0.05). Results of RT-PCR and Western blot showed that Notch1 mRNA and protein levels obviously decreased (P < 0.05).

CONCLUSIONAs2O3 could inhibit the expression of Notch1 and the cell proliferation and the migration force of SKBR-3 cells, which primarily revealed that As2O3 might affect the biological behavior of human breast cancer cells possibly through Notch1 signaling pathway, thus providing theoretical and experimental bases for treating breast cancer by arsenic.

Arsenicals ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Female ; Humans ; Oxides ; pharmacology ; RNA, Messenger ; genetics ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects

Objective To evaluate the mechanism of reduction of protection induced by hypoxic postconditioning (HPO) in diabetic myocardiocytes subjected to hypoxia-reoxygenation (H/R),and the relationship with DJ-1 expression.Methods H9c2 cells cultured in normal culture atmosphere were randomly divided into 6 groups (n=36 each) using a random number table:control group (group C),group H/R,group HPO,plasmid carrying DJ-1 gene transfection group (group D),plasmid carrying DJ-1 gene transfection + H/R group (group DH),and plasmid carrying DJ-1 gene transfection + H/R + HPO group (group DHH).H/R was induced by 4 h of hypoxia followed by 2 h of reoxygenation.H9c2 cells were cultured in high glucose culture medium (30 mmol/L) for 48 h in C,H/R and HPO groups.H/R model was established in H/R and HPO groups.HPO was induced by 3 cycles of 5 min reoxygenation and 5 min hypoxia before the onset of reoxygenation in group HPO.In D,DH and DHH groups,the plasmid carrying DJ-1 gene (pEX-2-EGFP-DJ-1) was transfected into the cells,and then the cells were cultured in high glucose culture medium and subjected to H/R and HPO,respectively.At 2 h of reoxygenation,the cell survival rate was measured using the cell counting kit-8 assay,and the level of lactate dehydrogenase (LDH) in the supernatant was detected by enzyme-linked immunosorbent assay,the autophagosomes were examined with a transmission electron microscope,and the expression of DJ-1 and p62 and ratio of microtubule-associated protein 1 light chain 3 Ⅱ / Ⅰ (LC3 Ⅱ / Ⅰ) in cells were detected by Western blot.Results Compared with group C,the cell survival rate and DJ-1 expression were significantly decreased,and the LDH activity was significantly increased in H/R and HPO groups (P＜0.01).There was no significant difference in the parameters mentioned above between H/R and HPO groups (P＞0.05).Compared with group D,the cell survival rate was significantly decreased,and the LDH activity was significantly increased in group DH (P＜0.01).Compared with group DH,the cell survival rate,the number of autophagosomes and LC3 Ⅱ / Ⅰ ratio were significantly increased,and the LDH activity and p62 expression were significantly decreased in group DHH (P＜0.01).There was no significant difference in the parameters mentioned above between H/R and DH groups (P＞0.05).Conclusion The mechanism of reduction of protection induced by HPO in diabetic myocardiocytes subjected to H/R is related to high glucose-induced inhibition of DJ-1 expression and decrease in autophagy.

Objective To investigate the effects of penehyclidine hydrochloride on activities of nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1) during actue lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation (HSR) in rats.Methods Thirty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly assigned into 3 equal groups (n =10 each) using a random number table:sham operation group (group S),blunt chest trauma-HSR group (group THSR) and penehyclidine hydrochloride group (group PHCD).The model of actue lung injury induced by blunt chest trauma-HSR was induced by dropping a 300 g weight onto a precordium in anesthetized rats.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.In PHCD group,PHCD 2 mg/kg was injected intravenously at 60 min after hemorrhagic shock.At 6 h after the model was established,blood samples were obtained for measurement of concentrations of tumor necrosis factor-alpha (TNF-α) in serum.The lungs were then removed for determination of lung water content,myeloperoxidase (MPO) activaty (by colorimetric assay),NF-κB and AP-1 activaties (using electrophoretic mobility shift assay) in lung tissues,and for microscopic examination of pathologic changes (under light microscope).The left lung was lavaged,and lung permeability index (LPI) was calculated.Results Compared with S group,lung water content,LPI,serum TNF-α level and activites of MPO,NF-κB and AP-1 were significantly increased in THSR and PHCD groups.Compared with THSR group,lung water content,LPI,serum TNF-α concentrations and activites of MPO,NF-κB and AP-1 were significantly decreased in PHCD group.The pathological damage to lung tissues was significantly reduced in PHCD group as compared with THSR group.Conclusion PHCD can inhibit activities of NF-κB and AP-1 in lung tissues,thus mitigating acute lung injury induced by blunt chest trauma-HSR in rats.

Objective To evaluate the relationship between DJ?1 and diabetes mellitus ( DM )?caused influence on cardioprotection induced by ischemic postconditioning in rats. Methods Adult male Sprague?Dawley rats, aged 3 months, weighing 220-250 g, were used in the study. DM was induced by intraperitoneal injection of 1% streptozotocin 60 mg∕kg and confirmed by blood glucose≥16.7 mmol∕L. Forty?eight rats with DM were randomly divided into 3 groups ( n=16 each) using a random number table:sham operation group ( group DM?S ) , myocardial ischemia?reperfusion ( I∕R ) group ( DM?IR ) and ischemic postconditioning group (DM?IPO group). Another 48 normal rats received the equal volume of citrate buffer solution instead and served as control. Those rats were randomly divided into 3 groups ( n=16 each) using a random number table: sham operation group ( S group) , myocardial I∕R group ( IR group) and ischemic postconditioning group (IPO group). At 12 weeks after streptozotocin injection, myocardial I∕R was produced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion. Ischemic postconditioning was induced by 3 cycles of 10 s reperfusion followed by 10 s limb ischemia at the end of 30 min limb ischemia. At 120 min of reperfusion, the animals were sacrificed, and hearts were removed for determination of myocardial infarction size ( using TTC ) , and expression of DJ?1, phosphatase and tensin homologue ( PTEN) protein, and phosphorylated Akt ( p?Akt) in myocardial tissues ( by Western blot) . Results The infarction size was significantly increased in diabetic and nondiabetic rats during myocardial I∕R. The expression of DJ?1, PTEN protein and p?Akt was significantly higher during myocardial I∕R in nondiabetic rats, and the expression of PTEN protein and p?Akt was up?regulated, and no significant change was found in DJ?1 expression during myocardial I∕R in diabetic rats. Ischemic postconditioning reduced infarction size during myocardial I∕R and up?regulated the expression of DJ?1 and p?Akt, and down?regulated the expression of PTEN protein in nondiabetic rats, but not in diabetic rats. Compared with nondiabetic rats, the expression of DJ?1 and p?Akt was down?regulated, and the expression of PTEN protein was up?regulated after ischemic postconditioning in diabetic rats. Conclusion The mechanism by which DM abolishes cardioprotection induced by ischemic postconditioning is associated with down?regulation of DJ?1 expression in rats.

Objective To investigate the expression in the VEGF,TGF-?1 of cervical squamous car- cinoma infected by HPV16,18.Methods Cells exfoliated from cervix(collected by clinician)of 99 women with cervical cancer and 54 women as a control group were analyzed blindly by human papillomavirus type 16 and 18 Fluorescent Polymerase Reaction Diagnositic kit.The expression of VEGF,TGF-?1 of the positive HPV16,18 of 38 women with cervical squamous cancer were studied by immunohistochemical stain.Results The positive expression of HPV16,18 was observed in 53 in the case of cervical cancer with positive rates of 54 %,but the positive rates was 7 % in the control group(P

Objective To investigate the numbers and the expression of MHC-Ⅰpositive cells in hu- man ovarian epithelial carcinoma tissues and provide the experimental data in the futher biological therapy of ovarian carcinoma.Methods Thirty one samples of ovarian epithelial carcinoma were analysed with flow cy- tometry for MHC classⅠexpression.Results The number of MHC classⅠcells(25.22?21.23,4.37?3.63)was fewer in ovarian epithelial carcinoma than that in normal ovarian tissues(43.56?18.47,7.43?5.87),and was related with pathologic grades(P

Objective To analyze if there are membrane estrogen receptors(ER)in endometrial carcinoma and if there is some relationship between membrane ER and nuclear ER.Methods The cell membrane and total cell ER?and ER?expressions of high and moderate differentiation endometrial carcinoma cells(Ishikawa and HEC-1A cells)were analyzed.Intermittent immunofluorescence dyeing and fluorescent microscopy were carried out with the ceils treated with polyformaldehyde and Triton X-100. Intermittent immunofluorescence dyeing and flow cytometry were carried out with the live cells and the cells treated with Triton X-100 respectively.Results There were fluorescences on the membrane of the Ishikawa and HEC-1A cells which were treated with polyformaldehyde.When the cells were treated with Triton X- 100,the fluorescences were also seen inside the cells.The fluorescence intensity of ER?and ER?in Ishikawa cell membrane(1.09?0.21,1.27?0.33)was stronger than the control,but there were no significant differences(P＞0.05).When treated with Triton X-100,the total cell fluorescence intensity of ER?and ER?in Ishikawa cell(4.21?0.34,4.69?1.96)was stronger than the membrane(P＜0.05). The ER?and ER?fluorescence intensity of HEC-1A cell membrane(1.58?0.13,1.49?0.04)were stronger than the control(P＜0.05).The fluorescence intensity of ER?and ER?of the HEC-1A cell (2.34?0.33,2.52?0.15)was stronger than the membrane also(P＜0.05).The membrane ER?fluorescence intensity of Ishikawa was lower than HEC-1A(P=0.028).But the total cell ER?fluorescence intensity of Ishikawa was higher than HEC-1A(P=0.002).Conclusions There are membrane ER on endometrial carcinoma cells Ishikawa and HEC-1A.The membrane ER must have some similarity to the nuclear receptor.There is no direct correlation between the quantity of the membrane ER and nuclear ER.