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OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.
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Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.
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Ziziphi Spinosae Semen (ZSS) is a common natural medicine used to treat insomnia, and to show clearly its method of action, we managed and did an in-depth discussion. Network pharmacology research is very suitable for the analysis of multiple components, multiple targets, and multiple pathways of Traditional Chinese Medicine (TCM). According to the relevant theory, we first carefully collected and screened the active ingredients in ZSS and received 11 active ingredients that may work. The targets going along with these active components were also strongly related to insomnia targets, 108 common genes were identified, and drug-compound-gene symbol-disease visualization network and protein-protein interaction network were constructed. Forty-eight core genes were identified by PPI analysis and subjected to GO functional analysis with KEGG pathway analysis. The results of GO analysis pointed that there were 998 gene ontology items for the treatment of insomnia, including terms of 892 biological processes, 47 cellular components, and 59 molecular functions. It mainly shows the coupling effect and transport mode of some proteins in the biological pathways of ZSS in the treatment of insomnia and explains the mechanism of action through the connection between the target and the cell biomembrane. KEGG enrichment analyzed 19 signaling pathways, which were collectively classified into seven categories. We have identified the potential pathways of ZSS against insomnia and obtained the regulatory relationship between core genes and pathways and know that the same target can be regulated by multiple components at the same time. The results of molecular docking also prove this conclusion. We sought to provide a new analytical approach to explore TCM treatments for diseases using network pharmacology analysis tools.
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Diabetes is associated with increased mortality from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq pancreas datasets and performed fluorescence in situ hybridization, Western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.
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Objective To explore and establish a method for quantitative evaluation of facial skin pores based on dermoscopy,and to evaluate the scientificity and practicability of this method.Methods Totally,30 patients with enlarged facial skin pores were enrolled from Department of Dermatology,Peking University Third Hospital between June 2017 and December 2017,and treated with 2 940 nm Er pixel laser.Photographs were taken,and dermoscopic images were collected before and after treatment.According to the standard photographs of facial pores,the improvement of enlarged facial pores was evaluated by comparing the photos before and after the treatment.A dermoscope-based pore detection system was established,and quantified indices for pore area and color difference before and after the treatment were evaluated by using this system.A pre-post self-contrast study was conducted,and statistical analysis was carried out by using paired t test for the comparison of measurement data and paired non-parametric test (Wilcoxon signed-rank test) for the comparison of ranked data.Results After the treatment,the standard photograph method for the assessment of facial pores showed score reduction by 3 grades in 1 of the 30 patients (3.3％),by 2 grades in 7(23.3％),by 1 grade in 21(70％),and no changes of grades in 1 (3.3％).Additionally,the differences between pre-and post-treatment grades were significant (Z =-4.94,P ＜ 0.01).The detection rate of skin pores by using the detection system was (70.59 ± 3)％.After the treatment,the quantified values of pore area and color difference both significantly decreased compared with those before the treatment (pore area:712.95 ± 87.45 vs.831.45 ± 88.92,t =5.70,P ＜ 0.05;color difference:23.82 ± 9.43 vs.28.92 ± 9.91,t =2.76,P ＜ 0.05).Conclusion The dermoscopy-based method for quantitative evaluation of skin pores after the treatment with 2 940 nm Er pixel laser showed highly consistent results with the standard photograph method,which can be further verified and popularized in the evaluation of enlarged skin pores.
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Objective To preliminarily validate the clinical usability of the ameliorated Kawashima Itch Scale(Xie-Kawashima Itch Scale) among adult pruritic patients on maintenance hemodialysis. Methods Xie-Kawashima Itch Scale was developed on the basis of Kawashima Itch Scale. Patients were asked to record their pruritus condition according to Xie-Kawashima Itch Scale or visual analogue scale(VAS) during daytime and night for two weeks. The record at the second week was used for analyzing the correlation between Xie-Kawashima Itch Scale and VAS. Results Totally 134 patients were enrolled in this study,among whom 128 entered the final analysis. Xie-Kawashima Itch Scale was positively correlated with VAS(r=0.832,95% CI=0.810-0.851,P<0.01 for daytime record;and r=0.848,95% CI=0.828-0.865,P<0.01 for night record). Subgroup analysis also showed similar correlations between different age groups and among different gender groups. Conclusion Xie-Kawashima Itch Scale has good correlation with VAS in patients on hemodialysis,without being affected by age or gender. Thus,it can be a useful tool for the assessment of pruritus in clinical practice and research.
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Objective To investigate the diagnostic value of rosette sign under a polarized dermoscope.Methods Lesions with rosette sign were selected from polarized dermoscopic image database of the Department of Dermatology of Peking University Third Hospital between September 2014 and March 2017.Then,histopathologically confirmed lesions were further chosen,and the correlations between the rosette sign and diseases were analyzed.These histopathologically confirmed lesions were divided into actinic keratosis (AK) group and non-AK group,and differences in clinical and dermoscopic features were analyzed between the 2 groups.Statistical analysis was carried out by nonparametric test for comparisons of the number of rosette sign between the AK group and non-AK group,as well as between different body sites.Results A total of 4 956 dermoscopic images of skin lesions were analyzed retrospectively,among which there were 144 (2.91％) skin lesions with rosette signs.Among the 144 skin lesions,74 were histopathologically diagnosed,37 (50.00％) of which were diagnosed as AK.Compared with the non-AK group,the AK group showed significantly higher proportions of lesions on the face (x2 =23.786,P ＜ 0.001) and at sun-exposed sites (x2 =12.921,P ＜ 0.001),and prevalence of superficial scales (x2 =7.056,P =0.008),keratotic plugs (x2 =6.167,P =0.013) and hair follicle openings surrounded by a white halo (x2 =4.893,P =0.027) under a dermoscope.Moreover,the number of rosette sign was significantly higher in facial lesions than in non-facial lesions (Z =-2.581,P =0.010),as well as in lesions at exposed sites than in those at unexposed sites (Z =-2.098,P =0.036).Conclusions The rosette sign is mainly observed in AK lesions.If lesions on the face or at sun-exposed sites are characterized by rosette sign,and superficial scales,keratotic plugs and hair follicle openings surrounded by a white halo can be observed under a dermoscope,these lesions can be diagnosed as AK with a high probability.
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Objective To investigate the value of dermoscopy in differential diagnosis of actinic keratosis (AK).Methods Pathologically confirmed facial AK lesions were selected from the dermoscopic database of Peking University Third Hospital,and served as case group.At the same time,the facial lesions of other diseases were selected and served as control group,which were firstly suspected to be AK,but pathologically confirmed as other diseases.Dermoscopic features were compared between the two groups.Diagnostic test was used to evaluate the diagnostic value of dermoscopy for AK,based on the gold standard pathological examination.Results There were 43 facial AK lesions in the case group and 22 facial lesions of other diseases in the control group.Eight dermoscopic features were observed more frequently in the case group than in the control group (all P ＜ 0.05),including a background erythema and red pseudonetwork (88.37％ [38/43] vs.36.36％ [8/22]),hair follicle openings surrounded by a white halo (90.70％ [39/43] vs.36.36％[8/22]),hair follicle openings filled with yellowish keratotic plugs (95.35％ [41/43] vs.45.45％ [10/22]),white to yellow surface scales or keratin mass (97.67％ [42/43] vs.72.73％[16/22]),rosette sign (60.47％ [26/43] vs.22.73％ [5/22]),large irregular linear vessels surrounding the hair follicles (44.19％ [19/43] vs.18.18％ [4/22]),fine,linear-wavy vessels surrounding the hair follicles (67.44％ [29/43] vs.36.36％ [8/22]) and peripheral pigmentation (32.56％ [14/43] vs.4.55％ [1/22]).Among the above eight dermoscopic features,hair follicle openings surrounded by a white halo,a background erythema and red pseudonetwork,hair follicle openings filled with yellowish keratotic plugs and rosette sign showed higher Youden's indices of 0.54,0.52,0.50 and 0.38 respectively,white to yellow surface scales or keratin mass showed the highest sensitivity of 97.67％,and peripheral pigmentation showed the highest specificity of 95.45％.The combination of 3 features (including a background erythema and red pseudonetwork,hair follicle openings surrounded by a white halo and follicular plugs) showed the highest diagnostic value,and the sensitivity,specificity,positive predictive value,negative predictive value and Youden's index of the combination were 90.70％,81.82％,90.70％,81.82％ and 0.73,respectively,with the coincidence rate between dermoscopy and pathological diagnosis being 80.00％.Conclusion Facial AK shows characteristic dermoscopy patterns,and the combination of the 3 features (a background erythema and red pseudonetwork,hair follicle openings surrounded by a white halo and follicular plugs) shows the highest diagnostic value for AK.
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We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 µM Cr and 0.06 µM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster.
Subject(s)
Arsenates/analysis , Arsenic/analysis , Carcinogens/analysis , Chromium/analysis , Copper/analysis , Wood/chemistry , Arsenates/toxicity , Arsenic/toxicity , Carcinogens/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Chromium/toxicity , Copper/toxicity , Humans , Incineration , Japan , Phosphatidylinositol 3-Kinases/metabolismABSTRACT
Noise stress generated in industry is one of the environmental factors that physically affects the functions of the inner ear. Exposure to noise can cause hearing loss, resulting in serious problems in occupational and daily life. At present, however, there are very limited ways to prevent hearing impairments. The inner ear consists of the organ of Corti, vestibule and semicircular canal. Functional or morphological damage of these tissues in the inner ear caused by genetic factors, aging or environmental factors can result in hearing or balance impairments. In this review, we first introduce a deafness-related molecule found by our clinical research. Our experimental research using genetically engineered mice further demonstrated that impaired activity of the target molecule caused congenital and age-related hearing loss with neurodegeneration of spiral ganglion neurons in the inner ears. We also describe impaired balance in mice caused by exposure to low-frequency noise under experimental conditions with indoor environmental monitoring. We believe that our approaches to pursue both experimental research and fieldwork research complementarily are crucial for the development of a method for prevention of impairments of the inner ear.
Subject(s)
Ear, Inner , Environmental Exposure/adverse effects , Hearing Loss/etiology , Noise/adverse effects , Occupational Exposure/adverse effects , Aging/pathology , Aging/physiology , Animals , Animals, Genetically Modified , Ear, Inner/anatomy & histology , Ear, Inner/innervation , Ear, Inner/pathology , Hearing Loss/prevention & control , Humans , Mice , Nerve Degeneration , Neurons/pathology , Noise, Occupational/adverse effects , Spiral Ganglion/pathologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate safety and immunogenicity of inactivated hepatitis A vaccine in HBsAg carriers and healthy children.</p><p><b>METHODS</b>One hundred and twenty-one healthy children and ten HBsAg carriers, aged 1-10 years HAV susceptible were enrolled in the study. The inactivated hepatitis A vaccine was produced by Tangshan Biogenetic Company. The dosage of the vaccine was 1000 U/Dosage and 500 U/Dosage. The vaccination schedule was six month apart for two injections. The serum anti-HAV level was detected with EIA at one month after first injection and at one and six month after the booster injection, respectively.</p><p><b>RESULTS</b>The anti-HAV appeared in all the children. One month after the booster injection, the serum anti-HAV level in children vaccinated 500 U/Dosage was 4684.9 mIU and 4535.6 mIU, respectively and in the children vaccinated 1000 U/Dosage, 5399.8 mIU and 7347.1 mIU, respectively. The anti-HAV level was not statistically different between the two groups of children. There was no adverse reaction after the vaccination. The anti-HAV level was still high one year after first injection.</p><p><b>CONCLUSIONS</b>The data indicated that the safety and immunogenicity of the domestic inactivated hepatitis A vaccine were excellent in both groups of children.</p>
