Objective: Developed the core-matched nanoemulsions (CMNEs) to co-delivery paclitaxel-oleic acid (PTX-OA) prodrug and Brucea javanica oil (BJO) for increasing the antitumor effect. Methods: Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology (CMT) were evaluated in vitro and in vivo. Results: The PTX-OA/BJO CMNEs were of nanoscale particle size (108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline (P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPO Ⅱ. Conclusion: Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.

Objective To definite the status of tone of autonomic nervous system during water immersion process by analyzing the nonlinear characteristic of ECG signals;To explore the relation of approximate entropy(ApEn),scaling exponent(?) changes and modulation function status of autonomic nervous system.Methods The ECG signals of rats during the process of restraint stress(RS),water-immersion restraint stress(WRS) and Vagotomy and Water-immersion restraint stress(vagotomy-WRS) were recorded.The ApEn and ? of RR intervals were calculated.Results After the stress,the differences of the value of ApEn and ? of RR intervals between RS and vagotomy-WRS groups and between different periods in vagotomy-WRS group were not significant.The value of ApEn increased in WRS group and decreased in RS group significantly.Compared with pre-stress,? showed decreased trend,all of the values smaller than 0.5 in WRS group and increased obviously,most values larger than 0.5 in RS group.Conclusion The increased ApEn and decreased ? indicates a higher intensity of parasympathetic activity.The parasympathetic activity is the predominant response of autonomic nervous system during water immersion process.

Background and purpose:Chemotherapy plays an important role in the treatment of breast carcinoma by inhibiting the tumor growth and inducing the apoptosis.MAPK transduction pathway is closely related to proliferation and apoptosis of varieties of tumor cells,inhibition of MAPK pathway may increase the efficiency and decrease the toxicity of chemotherapy.Our study was to investigate the effect of MEK inhibitor PD98059 in response of breast cancer cell lines to Epirubicin.Methods:Human breast cancer cell lines MCF-7 and MCF-7/ADR were used as cell models.Epirubicin(EADM),PD98059(inhibitor of MAPK Kinase-MEK),or EADM+PD98059 was added into the culture medium,the expression of MEK2 and p-ERK were measured by Western blot,the growth of the two cell lines were measured by MTT.Results:ERK activity was elevated in MCF-7 after the treatment of EADM,the cells were more sensitive to EADM if combined with PD98059,while in MCF-7/ADR,ERK activity kept unchanged after EADM treatment,and PD98059 has no effect on the sensitivity of cells to EADM.Conclusion:MAPK signal transduction may be activated in some cells treated by EADM,adding inhibitor of MAPK signal transduction could improve the sensitivity of the cells to EADM.

Abstract: Objective　To compare the mosquito trapping effect of BG-trap mosquito trap using carbon dioxide versus BG-lure attractant under filed conditions. Methods　In August and September 2020, two areas were set with a distance of 100 m. Two sites were set at each area, and one mosquito trap BG trap was set with a distance of 5 m. Each site was set with different flow of CO2 and different amount of BG-lure attractants. The BG-trap mosquito traps on the same area would exchange positions every other day. The mosquitoes captured by each mosquito trap was collected and classified. and the species, sex and number of mosquitoes captured were recorded and counted. Results　The densities of Aedes albopictus captured by BG+/CO2-and BG-/CO2+were 14 and 31, and that of Culex pipiens pallens were 2 and 16, respectively. The differences were statistically significant (Aedes albopictus, t=-2.675, P<0.05; Culex pipiens pallens, t=-4.873, P<0.05). With BG-lure attractant, the females of Aedes albopictus and Culex pipiens pallens in the CO2+group were 2.6 (25/9.5) and 12.0 (12 /1) times higher than those in the CO2-group, and the differences were statistically significant (female Aedes albopictus, t=-4.119, P<0.01; female Culex pipiens pallens, t=-4.592, P<0.01), suggesting that the most important attractant to female mosquitoes is CO2. With BG-lure attractant, the male Aedes albopictus in the CO2+ group was 3.0 (12/4) times higher than that in the CO2-group, and the difference was statistically significant (male Aedes albopictus, t=-3.284, P<0.01). Without BG-lure attractant, female Aedes albopictus and female Culex pipiens pallens in the CO2 + group were 1.8 (18 / 10) and 15.5 (15.5/1.0) times higher than those in the CO2-group, and the difference was statistically significant (female Aedes albopictus, t=-2.868, P<0.05; female Culex pipiens pallens, t=-5.259, P<0.05). Without BG-lure attractant, the male Aedes albopictus in the CO2+group was 2.0 (9.0/4.5) times higher than that in the CO2-group, with a statistically significant difference (t=-2.508, P<0.05). With CO2, Aedes albopictus and Culex pipiens pallens in the BG + attractant group were 1.4 (43.5/31) and 0.78 (12.5/16.0) times higher than those in the BG-attractant group, and the differences were not statistically significant (Aedes albopictus, t=-0.943, P>0.05 ; Culex pipiens pallens, t=0.709, P>0.05). Without CO2, Aedes albopictus and Culex pipiens pallens in the BG + attractant group were 1.0 (14/14) and 2.0 (2.0/1.0) times higher than those in the BG + attractant group, and the differences were not statistically significant (Aedes albopictus, t=-0.500, P>0.05; Culex pipiens pallens, t=-1.000, P>0.05). Without BG-lure attractant, the densities of female Aedes albopictus captured by adding 0, 1 and 2 parts of dry ice were 10, 17.5 and 18 respectively, and the difference was statistically significant among the three groups (F=3.942, P<0.05). The densities of female Culex pipiens pallens captured were 1, 13 and 18 respectively, and the difference was statistically significant among the three groups (F=13.881, P<0.05). However, there was no significant difference between the capture of female Aedes albopictus and female Culex pipiens pallens by adding 1 part of dry ice and 2 parts of dry ice (female Aedes albopictus, t=0.112, P>0.05; female Culex pipiens pallens, t=-0.540, P>0.05). Without CO2, 10, 10, 9.5 and 1, 1 and 1.5 female Aedes albopictus and Culex pipiens pallens were captured by adding 0, 1 and 2 portions of BG-lure attractants, respectively. There were no significant differences between the three groups (female Aedes albopictus, F=0.120, P>0.05; female Culex pipiens pallens, F=0.477, P>0.05). Conclusions　In the monitoring of BG-trap mosquito trap, the mosquito trapping effect of CO2 is better than that of BG-lure attractant. When the same monitoring effect is obtained, the use of CO2 (100 mL/min) can save the use cost.

Acute Disease ; Adult ; Combined Modality Therapy ; Fatty Liver ; therapy ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; therapy ; Treatment Outcome ; Young Adult

Thyroid cancer is the one of the most common endocrine tumors. The biological behaviors and prognoses of the thyroid cancer of different histological types remarkably differ. The highly invasive thyroid cancer responds poorly to traditional therapies. Recent research advances in the molecular mechanisms of the pathogenesis of thyroid cancer have revealed the roles of many genetic and epigenetic variations such as gene mutation, abnormal gene amplification, and abnormal gene methylation in the development of thyroid cancer, which provides new insights in the molecular diagnosis, prognosis, and target therapy of the thyroid cancer.
Carcinoma ; genetics ; Humans ; Mutation ; Signal Transduction ; Thyroid Neoplasms ; genetics

OBJECTIVETo investigate the expression of epidermal growth factor receptor (EGFR) during the mineralization of human periodontal ligament cells (hPDLC) in vitro.

METHODSStudies using specific antibodies to immunolocalize EGFR in the mineral differentiating hPDLC were undertaken to investigate the different expression during the inducing process. In situ hybridization and RT-PCR technique were used to investigate the transcripts encoding the protein of EGFR.

RESULTSThe results showed that immunocytochemical labeling gradually decreased following the elong of the induce time, downing to nearly negative at the 4th week and the signal of EGFR transcripts was weaker in the induced hPDLC than that in uninduced.

CONCLUSIONEGFR has a negative regulation function during the mineralization of hPDLC.

Cells, Cultured ; Humans ; In Situ Hybridization ; In Vitro Techniques ; Periodontal Ligament ; Receptor, Epidermal Growth Factor

OBJECTIVETo study the inhibitory effect of paeoniflorin (PAE) on TNF-α-induced TNF receptor type I (TNFR1)-mediated signaling pathway in mouse renal arterial endothelial cells (AECs) and to explore its underlying molecular mechanisms.

METHODSMouse AECs were cultured in vitro and then they were treated by different concentrations PAE or TNF-α for various time periods. Expression levels of intercellular cell adhesion molecule-1 (ICAM-1) were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 6-h TNF-α 30 ng/mL), the low dose PAE group (cultured by 2-h PAE 0.8 μmo/L plus 6-h TNF-α 30 ng/mL), the middle dose PAE group (cultured by 2-h PAE 8 μmol/L plus 6-h TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 6-h TNF-α 30 ng/mL) with Western blot analysis. Nuclear translocation of transcription factor NF-κB (NE-κB) was detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 45-mm TNF-α 30 ng/mL), and the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 45-min TNF-α 30 ng/mL) by immunofluorescent staining. Expression levels of the phosphorylation of extracellular signal-regulated (protein) kinase (ph-ERK) and p38 (ph- p38) were detected in the normal group (cultured by serum-free culture media) and the high dose PAE group (2-h PAE 80 μmol/L culture) by Western blot. NF-κB inhibitor-α (IκBα) protein expressions were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 30-min TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 30-min TNF-α 30 ng/mL), the p38 inhibitor group (SB group, pretreatment with SB238025 25 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min), the ERK inhibitor group (PD group, treated by PD98059 50 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min) by Western blot.

RESULTSCompared with the normal group, ICAM-1 protein expression levels obviously increased (P < 0.01). Compared with the TNFα group, ICAM-1 protein expression levels were obviously inhibited in the high dose PAE group (P < 0.05). Protein expression levels of ph-p38 and ph-ERK were obviously higher in the hIgh dose PAE group (P < 0.05). Compared with the normal group, IκBα protein expression levels obviously decreased in the TNF-α group (P < 0.01). Compared with the TNFα group, TNF-α-induced IκBα degradation could be significantly inhibited in the high dose PAE group (P < 0.01); the inhibition of PAE on IκBα degradation could be significantly inhibited in the SB group (P < 0.05). NF-κB/p65 signal was mainly located in cytoplasm in the normal group. NF-κB/p65 was translocated from cytoplasm to nucleus after stimulated by 45 min TNF-α in the TNF-α group, while it could be significantly inhibited in the high dose PAE group.

CONCLUSIONSPAE inhibited TNF-α-induced expression of lCAM-1. Its action might be associated with inhibiting TNFR1/NF-κB signaling pathway. p38 participated and mediated these actions.

Animals ; Cells, Cultured ; Endothelial Cells ; cytology ; drug effects ; Glucosides ; pharmacology ; Intercellular Adhesion Molecule-1 ; metabolism ; Mice ; Monoterpenes ; pharmacology ; NF-kappa B ; metabolism ; Receptors, Tumor Necrosis Factor ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with diabetes.

METHODSStearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats in NC group were injected with 0.05 mmol/L citrate buffer as control. One week later, dorsal skin of rats in AI and MI groups were respectively treated with 10 g/L aminoguanidine cream and matrix cream by external use for 4 weeks. AGE content was determined with fluorescence detection from skin collagen extract. KC cell cycle was detected by flow cytometry. Skin tissue specimens were obtained for determination of levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), and total antioxidant capacity. Data were processed with t test.

RESULTSTransdermal effect of aminoguanidine cream with dose of 10 g/L was better than that with 5 g/L or 5 g/L + 10 g/L azone cream. One rat was not induced successfully in MI group. Four weeks after model reproduction, 4 rats died in D group and 1 rat died in AI group. The AGE content in D group was obviously higher than that in NC group [(36.8 +/- 2.6), (24.6 +/- 2.7) U per milligram hydroxyproline, respectively, t = 7.2, P < 0.01], and that in AI group [(28.6 +/- 3.7) U per milligram hydroxyproline] was also lower as compared with that in D group (t = -3.9, P < 0.05). There was no significant difference in AGE content between MI [(32.2 +/- 5.2) U per milligram hydroxyproline] and D groups (t = 1.6, P > 0.05). The percentage of KC in S phase was obviously lower in D group than in NC group [(5.3 +/- 0.6)%, (7.6 +/- 0.9)%, respectively, t = 4.50, P < 0.01], while that in MI group [(9.2 +/- 1.5)%] was higher as compared with that in D group ( t = 4.90, P < 0.01). It was more higher in AI group than in D group on KC percentage in S and G2/M phase (with t value respectively 6.80, 3.17, P values all below 0.01). The oxidative stress indexes of skin tissue in D group were all higher than those in NC group, in which levels of MPO and SOD showed statistical difference (with t value respectively 4.4, 3.7, P values all below 0.05). The oxidative stress indexes were all lower in AI group than in D group, especially in SOD level (t = -1.4, P < 0.05). Levels of MAD, MPO in MI group were significantly lower than those in D group (with t value respectively 2.6, 2.9, P values all below 0.05).

CONCLUSIONSAminoguanidine cream can promote KC proliferation and appropriately reduce oxidative stress through inhibiting AGE formation to a certain extent in skin tissue of rats with diabetes. Signal use of matrix cream can also reduce oxidative stress in skin tissue of rats with diabetes.

Administration, Cutaneous ; Animals ; Cell Proliferation ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Glycation End Products, Advanced ; metabolism ; Guanidines ; administration & dosage ; pharmacology ; Keratinocytes ; drug effects ; Male ; Ointments ; administration & dosage ; pharmacology ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; pathology

OBJECTIVETo separate and identify the chemical constituents of Blumea riparia.

METHODThe compounds were separated and purified by repeated silica gel, Sephadex LH -20 column chromatographiy. The structures of these compounds isolated were identified by analysis of their spectral data, physical and chemical properties.

RESULTSix flavonoids were isolated from B. riparia. and their structures were identified as eriodictyol-7, 4'-dimethyl ether (1), eriodictyol-7, 3'-dimethyl ether (2), eriodictyol-7-methyl ether (3), quercetin-7, 3', 4'-trimethyl ether (4), tamarixetin (5), rhamnocitrin (6).

CONCLUSIONCompound 1-6 were obtained from B. riparia for the first time.

Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Flavonoids ; analysis ; isolation & purification ; Magnetic Resonance Spectroscopy