Hair follicle (HF), one of the skin appendages, has received a lot of attention to be a new target and pathway for drug delivery. The development of hair follicle targeted drug delivery system (HFTDDS) through percutaneous permeation is particularly important for skin diseases derived from HF such as acne, hair loss, and folliculitis for their on-site action. This review describes the structure and physiological function of HF, the microenvironment of HF, and factors affecting HF permeation. Multiple nanoformulations used to improve the HF permeation and technologies to characterize the HF permeation were introduced. The latest advance of HFTDDS based on nanoformulations were systematically summarized and analyzed in the treatment of acne and hair loss. Finally, the challenges of formulating HFTDDS were discussed. The review is expected to provide some ideas and references for developing delivery systems for treating skin diseases derived from HF.

astaxanthin is an effective antioxidant and natural pigment which has wide application. Phaffia rhodozyma is a good source of astaxantin, but wild strain has limited use in industry because of low production level of astaxanthin. Several mutants of Phaffia rhodozyma were obtained by exerting mutagen N-methyl-N-nitro-N -nitrosoguanidine. The growth curve suggested that pigments were mainly produced in the middle and latter periods of log phase. The pigments were extracted from Phaffia rhodozyma and analysed by esterification, thin layer chromatography and absorption spectrometry. It was proved that astaxanthin, astaxanthin diester and ?-carotene were the major components of the pigments produced by Phaffia rhodozyma. We also studied the pigments producing phase of Phaffia rhodozyma. and founded that astaxanthin was stable to light under butylated hydroxytoluene coexistance.

OBJECTIVE: To analyze the cases of anaphylactic death cases and explore the standards of judicial expertise of anaphylactic death for providing evidence for judicial expertise. METHODS: Fifty-nine cases death due to allergic reaction in Shanghai were collected. And details of medical history, clinical manifestation of anaphylactic reaction and postmortem examination findings were reviewed for all cases. RESULTS: In the 59 cases, there were 58 cases died from drug allergy, including 77.6% of them were antibiotics. The rates of treating in standard hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic symptoms were dyspnea and facial cyanosis. The time from contacting allergens to death ranged from 1 min to 3 d. The concentration of total serum IgE ranged from 50 to 576.92 IU/mL. The results of clinical manifestation and pathological anatomy had obviously changes. CONCLUSION Based on the exclusion of all other cause of death and synthetically analysis of details of cases, medical history, clinical manifestation and anatomy, the conclusion of anaphylactic death can reached. The details of cases including clinical history, exposure to allergens, and clinical manifestation play an important role in diagnosis of anaphylactic death.
Anaphylaxis/mortality* ; Anti-Bacterial Agents/adverse effects* ; Autopsy ; China ; Drug Hypersensitivity/mortality* ; Forensic Sciences ; Humans

To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.
Calorimetry, Differential Scanning ; Curcumin ; chemistry ; Drug Liberation ; Lactic Acid ; Microscopy, Electron, Scanning ; Microspheres ; Polyglycolic Acid ; X-Ray Diffraction

This study was purposed to investigate the angiogenesis-promoting activities of human mesenchymal stem cells (hMSCs) modified by hepatocyte growth factor (HGF) and the underlying mechanisms. The hMSCs were transfected by recombinant adenoviral vector carrying human HGF gene and seeded onto the chicken chorioallantoic membrane. Three days later, the number of blood vessels was counted and their angiogenic response was compared with those of hMSCs of same generation, recombinant basic fibroblast growth factor (bFGF) and alpha-MEM as control. The expression levels of bFGF, VEGF, angiopoietin-1 and angiopoietin-2 were evaluated by RT-PCR assay. The results showed that gene-modified hMSCs exhibited greatest activity to promote angiogenesis while the angiogenic response was nearly same between groups treated by hMSCs and bFGF, all of which were significantly higher than that observed in control (p < 0.01). RT-PCR analysis revealed that hMSCs constitutively expressed multiple angiogenesis-associated growth factors and their levels seemed up-regulated by HGF gene transfer. It is concluded that HGF gene-modified hMSCs show a potent angiogenesis-promoting function and may be useful in the treatment of ischemic disorders.
Animals ; Cells, Cultured ; Chick Embryo ; Chickens ; Hepatocyte Growth Factor ; genetics ; Humans ; Mesenchymal Stromal Cells ; Neovascularization, Physiologic ; genetics ; Transfection

Objective To detect the expression of metallothionein-3 (MT-3)mRNA in human esophageal squamous cell carcinoma. Methods Five cell lines of human esophageal cancer,TE-1,TE-13,TTN,ECA-109 (cell lines of esophageal squamous cell carcinoma) and OE33 (cell lines of esophageal adenocarcinoma),were used in this study. RT-PCR was employed to detect the expression of MT-3 mRNA. Peripheral blood monouclear cells from normal subjects were served as controls. Results Sequencing of RT-PCR product certified the gene of MT-3 mRNA. It was revealed by gel electrophoresis that there was expression of MT-3 mRNA in each cell line. The relative expression of MT-3 mRNA was 0.230?0.023,0.516?0.020,0.140?0.009,0.176?0.015 and 0.085?0.011 in cell lines of TE-1,TE-13,TTN,ECA-109 and OE33,respectively,significantly lower than that in controls (0.762?0.026) (P

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.