[Signaling Pathways in the Pathogenesis of Acne Vulgaris].

Acne vulgaris is an inflammatory disease of hair follicle sebaceous gland units,with an incidence of up to 85% in adolescents.The pathogenesis is closely related to androgen,sebum secretion,lipophilic microbial infection,and immune-inflammatory reaction.This article reviews the signaling pathways related to acne from the aspects of inflammatory signaling pathways and sebum secretion pathways.

[Insulin Resistance and Skin Diseases].

Insulin resistance refers to a pathological condition in which cells fail to respond sufficiently to insulin,leading to impaired glucose uptake and utilization. In recent years,some skin diseases have been found to be associated with metabolic syndrome,and insulin resistance is considered to be the most important pathophysiological feature of the metabolic syndrome. Recent literatures have described the role of insulin resistance in the pathogenesis of these skin diseases. This article elucidates the mechanisms of insulin resistance involved in skin diseases.

[Insulin-like Growth Factors and Dermatosis].

Insulin-like growth factors(IGFs)are polypeptides structurally homologous to insulin.By binding to membrane tyrosine receptors,they regulate the proliferation,differentiation,apoptosis,growth,and development of body cells and are involved in the pathogenesis of tumors and other diseases.In recent years,more research on IGFs of dermatosis increased.This article reviews recent research advances in IGFs and its relationship with dermatosis.

Notoginsenoside R1 Promotes the Growth of Neonatal Rat Cortical Neurons via the Wnt/ß-catenin Signaling Pathway.

BACKGROUND & OBJECTIVE: Notoginsenoside R1 (NGR1) is one of the main effective components of Panax notoginseng. METHOD: Primary cortical neurons were harvested from neonatal rats and cultured to analyze the role of NGR1 in neuronal growth and the effects of NGR1 on the Wnt/ß-catenin signaling pathway. Following treatment with NGR1, immunocytochemistry was used to detect expression of Tuj1 and MAP2, and RT-qPCR was used to measure mRNA levels of key factors in the Wnt signaling pathway. RESULTS: Results showed that NGR1 promotes growth of cultured neurons and significantly upregulates mRNA levels of ß-catenin, Dishevelled, and Frizzled. To further confirm whether NGR1 promoted cortical neuron growth via the Wnt/ß-catenin signaling pathway, we knocked down ß- catenin mRNA by siRNA interference; following NGR1 treatment of ß-catenin-knockdown neurons, ß-catenin mRNA levels increased significantly. CONCLUSION: In conclusion, these results demonstrate that NGR1 promotes growth of cultured cortical neurons from the neonatal rat, possibly via the Wnt/ß-catenin signaling pathway.

[Value of CD, MPO, Ki-67 and C-MYC Positive Rate in the Pathological Tissues and C-MYC Gene of Patients with T-LBL/ALL for Predicting Prognosis].

OBJECTIVE: To explore the value of of CD, MPO, Ki-67, C-MYC positive rates in the pathological tissues and C-MYC gene of patients with T-LBL/ALL for predicting Prognosis. METHODS: Ninty cases of T-LBL/ALL patients in our hospital were selected and included in the T-LBL/ALL group, and 30 cases of lymphnode reactive hyperplasia were selected as control group. Immunohistochemical staining was used to detect the changes of CD, MPO, Ki-67 and C-MYC positive rate in 2 groups, and the changes of C-MYC gene were detected by fluorescence in situ hybridization. RESULTS: In 90 patients with T-LBL/ALL, there were CD1a+ 34 cases (37.8%), CD3+ 67 cases (74.4%), epsilon CD3+ 47 cases (52.2%), CD7+ 85 cases (94.4%), CD10+ 33 cases (36.7%), CD34+ 22 cases (24.4%), CD43+ 48 cases (53.3%), CD45RO+ 46 cases (51.1%), CD99+ 88 cases (97.8%), TDT+ 85 cases (94.4%); and CD23, CD20, and MPO all were negative; Ki-67>80% 47 cases (52.2% cases), Ki-67≤80%, 43 cases (47.8%). In 90 T-LBL/ALL patients, the positive rate of C-MYC (66.7%) was significantly higher than the control group (positive rate 0.0%) (P< 0.05); the Ki-67 index, mediastinal widening of T-LBL/ALL patients and the positive rate of C-MYC positively were correlated (P< 0.05). The overall survival rate (44.0%) of C-MYC negative patients was significantly higher than that of C-MYC positive patients (0.0%). The overall survival rate of C-MYC negative patients was significantly higher than that of C-MYC positive patients (P< 0.05).Ann Arbor staging, LDH, bone marrow involvement, mediastinal widening, Ki-67 positive index, and C-MYC protein expression of patients with T-LBL/ALL did not correlated with increased C-MYC gene breakage and copy number (P> 0.05). CONCLUSION: The overall survival rate of C-MYC positive patients decreases, which positively correlates with Ki-67 positive index and mediastinal width, suggesting that the prognosis of the patients with C-MYC protein expression is poorer.

[Comparison of different administration routes of saikosaponin in plasma pharmacokinetics and brain pharmacokinetics].

To evaluate the optimum administration routes of saikosaponin in the treatment of epilepsy by comparing the plasma pharmacokinetics and the brain pharmacokinetics after different administration routes of saikosaponin. After receiving saikosaponin in different administration routes, the mice were sacrificed to collect the blood and brain tissues. The acetonitrile and methanol (9∶1) were used to precipitate the plasma protein. The concentration of the SSa in mice plasma and brain was determined by UPLC-MS/MS, and the pharmacokinetic parameters, bioavailability, the brain targeting coefficient (Re) and the brain drug targeting index (DTI) were calculated with Kinetica software. The relative brain Re was 142.17% by intranasal administration, with DTI of 3.06, significantly higher than those by the injections; in addition, the brain DTI was 1.25 by gavage administration. The brain drug targeting of saikosaponin by intranasal administration was higher than that by injection and gavage administration, indicating the advantages of the intranasal administration on medicine absorption into the brain.

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer.

Caudatin, a C-21 steroidal glyco-side isolated from Chinese herbs, has a long history of use for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of caudatin in human uterine cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which caudatin inhibits cell growth in human cervical carcinoma cell line (HeLa) and endometrial carcinoma cell line (HEC-1A). Treatment with caudatin promoted cell morphology change, inhibited cell proliferation, colony formation, migration and spheroid formation, and induced cell apoptosis. Our results showed that the expression of tumor necrosis factor; α-induced protein 1 (TNFAIP1) was downregulated in uterine cancer cells and tissues compared to paired adjacent non-tumor uterine tissues. Further molecular mechanism study showed that caudatin can directly regulate TNFAIP1 expression in a concentration-dependent manner and also associated with the downregulation of NF-κB and upregulation of BAX/BcL-2 ratio and caspase-3. Moreover, we found that overexpression of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in uterine cancer cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer. We found that caudatin inhibited tumorigenicity and upregulated TNFAIP1 in vivo. Taken together, caudatin impacts on cell proliferation, migration and apoptosis of uterine cancer cells by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of TNFAIP1/NF-κB signaling. Our findings provide new insights into understanding the anticancer mechanisms of caudatin in human uterine cancer therapy.

[Pharmacokinetics of bullatine A in Aconitum brachypodum total alkaloids gel in transdermal delivery].

In this study, the changes of bullatine A in plasma and skin of mice with time in microemulsion gel and ordinary gel of Aconitum brachypodum total alkaloids were compared through UPLC-MS/MS, and their pharmacokinetic parameters were also compared and analyzed, to investigate the feasibility of microemulsion agent in the transdermal drug delivery. UPLC-MS/MS method for simultaneous determination of bullatine A in plasma and skin had high sensitivity and was in line with the pharmacokinetic study requirements for transdermal drug delivery. The main pharmacokinetic parameters for microemulsion gel in the plasma were as follows: Cmax=(37.62±14.31) µg•L⁻¹, Tmax=(3.40±1.34) h, AUC0-∞=(1 027.7±260) µg•L⁻¹â€¢h⁻¹, MRT=(34.80±12.31) h, MRTlast=(10.68±0.57) h, t1/2=(23.11±9.20) h; main pharmacokinetic parameters for ordinary gel in the blood: Cmax=(52.23±15.90) µg•L⁻¹, Tmax=(4.00±0.00) h, AUC0-∞=(728.60±280.80) µg•L⁻¹â€¢h⁻¹, MRT=(20.69±3.98) h, MRTlast=(9.34±0.42) h, t1/2=(14.69±3.15) h. The results showed that the microemulsion gel had more stable transdermal absorption, longer duration of action and higher bioavailability than ordinary gel, indicating that the microemulsion gel had a good and stable transdermal effect. There was no significant difference in bioavailability of bullatine A in skin between microemulsion gel and ordinary gel.

[In vitro recovery rate of bullatine A microdialysis probe].

To establish UPLC-MS/MS method for determination of the recovery rate of bullatine A microdialysis probe. The concentration difference method(incremental method, decrement method) was used to measure in vitro recoveries, and the effects of perfusate pH value, flow rate, concentration, and temperature on the recovery rate were investigated to explore the feasibility of microdialysis for the pharmacokinetic study of bullatine A. The method of UPLC-MS/MS showed good linear relationship within the required range; the specificity, recovery rate and precision of chromatography met the requirements of microdialysis samples. There was no significant difference in the measured recovery rate between incremental method and decrement method. Under the same conditions, in vitro recovery rate of the probe was decreased with the increase of flow rate, and was significantly increased with the increase of temperature, but was independent of bullatine A concentrations around the probe. The results showed that, microdialysis technology can be used for the pharmacokinetic study of bullatine A, and retrodialysis method (decrement method) can be used for the determination of the in vivo recovery rate of bullatine A microdialysis.

[Anolyte enhanced electrokinetic remediation of fluorine-contaminated soils].

An experimental study was carried out in order to determine the characteristics of migration and its influencing factor of soil fluorine in the electrokinetic process under different applied voltage and concentration of anolyte. The feasibility of anolyte enhanced on electrokinetic remediation of fluorine-contaminated soil was analyzed. The results show that when deionized water is used as anolyte with the 1.0 V/cm voltage gradient, the cumulative mass of fluorine in catholyte and anolyte are 8.2 mg and 47.7 mg respectively and the removal rate of fluorine is only 8.8%. Anolyte enhanced electrokinetic process can promote effectively the migration of fluoride in soil. When 0.02 mol/L NaOH solutionis employed as the anolyte, the removal rates are 25.9%, 31.2% and 47.3% with 1.0, 1.5 and 2.0 V/cm voltage gradient respectively. As the concentration of anolyte increased to 0.1 mol/L, the removal rates are 55.4%, 61.1% and 73.0%. The electromigration is the main transport mechanism and the electroosmotic flow has an effect on the migration of fluorine in soil. The voltage gradient and the concentration of anolyte are the main factors influencing the removal rate of fluorine in soil. Appropriate anolyte enhanced electrokinetic method can be applied to remediate fluorine from contaminated soil.