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AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Criança , Humanos , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , China/epidemiologia , Sistema de RegistrosRESUMO
Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Infecções por Papillomavirus , Animais , Camundongos , Proteínas Hedgehog/genética , Carcinoma de Células Escamosas do Esôfago/genética , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Neoplasias Esofágicas/genética , Camundongos NusRESUMO
Grazing is one of the most important management practices for grasslands. To date, most studies on how grazing affects plant diseases have focused on a single plant species, ignoring plant community characteristics and phylogeny. We used data from a 6-year yak grazing experiment (0, 1, 2, and 3 yak(s) ha - 1 treatment) in an alpine meadow ecosystem of Qinghai-Tibetan Plateau, from which we tested grazing effects on foliar fungal diseases at both population and community levels. By measuring plant community variables (including richness, evenness, phylogenetic diversity, and composition) and disease severity, we evaluated the relative importance of plant community-mediated effects of yak grazing on community pathogen load with a multi-model inference approach. We found significant differences in pathogen load among different grazing treatments; we recorded the highest and lowest pathogen loads in the 1 yak ha - 1 treatment and in the 3 yaks ha - 1 treatment, respectively. Pielou's evenness index and community proneness (i.e., an estimate of the capacity of plant communities to support diseases) best explained variation in pathogen load, indicating that plant community-mediated effects (through evenness and proneness) of yak grazing determined pathogen load. Our study provides empirical evidence that grazing influences foliar fungal disease prevalence through plant community evenness and composition, which demonstrates the necessity of incorporating host plant community characteristics into disease load prediction frameworks.
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Herbivoria , Micoses , Doenças das Plantas , Biodiversidade , Ecossistema , Filogenia , PlantasRESUMO
Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.
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Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Metionil Aminopeptidases/genética , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Linhagem Celular Tumoral , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Ovário/patologia , Ovário/cirurgia , Análise Serial de Tecidos , Regulação para CimaRESUMO
This aim of this study was to observe the effect of Yang Yan Qing E Wan (YYQEW) on senescent phenotypes and the expression of ß-catenin and p16INK4a in the hydrogen peroxide (H2O2)-induced premature senescence of normal human skin fibroblasts (NHSFs). Primary normal human skin fibroblasts were randomly divided into a normal group, a blank group, a model group, and a YYQEW group. The cells of the model group and the YYQEW group were exposed to 150 µmol/L H2O2 for 2 h. The morphological changes of the cells were analyzed by microscopy and by kits used to estimate the activities of the senescence-associated ß-galactosidase (SA-ß-gal), reactive oxygen species (ROS), and superoxide dismutase (SOD). The outcomes revealed that dyeing rate proportion of SA-ß-gal was 2.78% ± 0.22% in the normal group, 2.83% ± 0.29% in the blank group, 37.58% ± 2.56% in the model group, and 28.39% ± 0.93% in the YYQEW group. The number of SA-ß-gal positive cells was thus significantly higher in the model group than in the normal or blank group. There were also fewer SA-ß-gal positive cells in the YYQEW group compared with the model group. The expression of ROS and p16INK4a in the model group increased significantly compared with that in the normal or blank groups, while the expression of ROS and p16INK4a in the YYQEW group decreased significantly compared with that in the model group. The expression of SOD and ß-catenin in the model group decreased significantly compared with that in the normal or blank group, and the expression of SOD and ß-catenin in the YYQEW group increased significantly compared with that in the model group. Overall, it was found that YYQEW was able to delay the senescence of NHSFs induced by H2O2 treatment by alleviating oxidative stress and regulating a number of senescence-related molecules, such as ß-catenin and p16INK4a.
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Envelhecimento/fisiologia , Senescência Celular/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Pele/fisiopatologia , beta Catenina/análise , Animais , Senescência Celular/genética , Modelos Animais de Doenças , Fibroblastos/citologia , Humanos , Peróxido de Hidrogênio/farmacocinética , Peróxido de Hidrogênio/uso terapêutico , Estresse Oxidativo , Fenótipo , Ratos Sprague-Dawley , Pele/citologiaRESUMO
The esophagus is a pivotal organ originating from anterior foregut that links the mouth and stomach. Moreover, its development involves precise regulation of multiple signal molecules and signal transduction pathways. After abnormal regulation of these molecules in the basal cells of the esophagus occurs, multiple diseases, including esophageal atresia with or without tracheoesophageal fistula, Barrett esophagus, gastroesophageal reflux, and eosinophilic esophagitis, will take place as a result. Furthermore, expression changes of signal molecules or signal pathways in basal cells and the microenvironment around basal cells both can initiate the switch of malignant transformation. In this review, we highlight the molecular events underlying the transition of normal development to multiple esophageal diseases. Additionally, the animal models of esophageal development and related diseases, challenges, and strategies are extensively discussed.
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Esôfago/metabolismo , Refluxo Gastroesofágico/metabolismo , Metástase Neoplásica/patologia , Neoplasias/patologia , Células-Tronco/citologia , Animais , Modelos Animais de Doenças , Esôfago/patologia , Refluxo Gastroesofágico/patologia , Humanos , Neoplasias/metabolismo , Células-Tronco/metabolismoRESUMO
The morphologies of PEMA-RB/PHEMA semi-interpenetrating polymeric network (semi-IPN) blended membranes prepared via ultraviolet (UV) promoted in situ photopolymerization were investigated using laser scanning confocal fluorescence microscopy (LSCFM). The results show that the semi-IPN morphology generated through UV light irradiation-induced microphase separation is considerably dependent on the relative rates of the photochemical reaction and microphase separation in the reactive precursor mixtures, which are determined by reactive dynamic factors. Changing the dynamic conditions, such as the UV light intensity, content of cross-linker and concentration of HEMA photopolymerization monomer resulted in a corresponding alteration of the morphological structure in the semi-IPN membranes. The hierarchical morphology appearing in the PEMA-RB/PHEMA semi-IPN should be related to the inhomogeneous photoreaction dynamics of the mixed system. Desired morphologies of the semi-IPN blend membranes can be obtained by controlling the corresponding dynamic conditions of both the photochemical reaction and microphase separation.
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Materiais Biocompatíveis , Membranas Artificiais , Poliésteres/química , Raios Ultravioleta , Microscopia de FluorescênciaRESUMO
Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective management. The precise underlying causes of melasma remain elusive, and the current therapeutic approaches predominantly encompass pharmaceutical and laser interventions, with limited efficacy. Transdermal administration stands as a prevalent treatment method for melasma, often facilitated by the application of microneedles. Among these, tranexamic acid emerges as a frequently employed therapeutic agent. A subset of microneedles, known as roller microneedles, plays a significant role in this approach by delicately puncturing the epidermis with multiple fine needles, synergizing with drug delivery. This methodology not only enhances drug absorption but also augments treatment efficacy while minimizing tissue trauma. These attributes forecast promising avenues for the treatment of melasma. This article primarily introduces the combination of roller microneedle and tranexamic acid solution in the treatment of melasma and demonstrates the efficacy of roller microneedle and tranexamic acid solution in the treatment of melasma through clinical cases.
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Melanose , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Administração Cutânea , Resultado do Tratamento , Melanose/tratamento farmacológico , Administração OralRESUMO
Plant litter decomposition is critical for carbon and nutrient cycling globally. However, the effect of large herbivore grazing on litter decomposition and its mechanisms remain less explored. Here, 1203 paired observations and 381 independent experiments were analyzed to determine how litter decomposition and nutrient cycling respond to changes in grazing intensity. Grazing significantly increased litter decomposition rate by 14.08 % and litter carbon release by 5.03 %, and this effect was observed in grasslands and croplands but not in forests. The positive grazing effect was also found under sheep and cattle/yak grazing. Moderate grazing advanced the home-field advantage effect but inhibited under heavy grazing for grazed litters. The grazing effect was larger for high quality litter than for low quality litter. Litter decomposition slowed under >10 years heavy grazing but accelerated under moderate grazing. The effects of large herbivore grazing on litter decomposition were jointly influenced by grazing intensity, livestock type, climate condition, decomposition duration, litter quality, and soil properties. Our results demonstrated that large herbivore grazing accelerates litter decomposition globally and emphasized the significance and importance of grazing intensity on litter decomposition, which should be integrated into terrestrial ecosystem models.
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Ecossistema , Herbivoria , Bovinos , Animais , Ovinos , Nitrogênio , Florestas , Solo , Carbono , Folhas de PlantaRESUMO
Objective: To investigate the variation of ferroptosis-related markers in HaCaT cell photoaging models induced by ultraviolet-B (UVB). Methods: UVB-treated HaCaT cells served as the model (UVB group) for cellular photoaging, whereas untreated HaCaT cells served as the control group. HaCaT cells were exposed to UVB and the ferroptosis inhibitor Ferrostatin-1 (Fer-1) as part of the UVB+Fer-1 group, and co-cultured with the ferroptosis inducer Erastin as part of the UVB+Erastin group. Reactive oxygen species (ROS) detection kit and senescence-related ß galactosidase (SA-ß-gal) staining were used to evaluate the senescence of HaCaT cells. Lipid reactive oxygen species were detected by C11 BODIPY581/591 probe and mitochondrial morphology was observed by transmission electron microscopy. The mRNA expressions of glutathione peroxidase 4 (GPX4) and ferroptosis-suppressor-protein 1 (FSP1) were detected by real-time reverse transcription-PCR (RT-RCP), and the level of GPX4 protein was measured by immunofluorescence assay. Results: The UVB group had considerably greater levels of ROS, SA-ß-gal, and lipid reactive oxygen species than the control group. The UVB group's mitochondrial volume was reduced, the membrane density increased, and the mitochondrial crest decreased or even disappeared. GPX4 and FSP1 expression levels were similarly found to be lower in the UVB group. Furthermore, the positive rate of SA-ß-gal and lipid reactive oxygen species in the UVB+Fer-1 group was much lower than in the UVB group, but it was reverse in the UVB+Erastin group. This study showed that induced ferroptosis can aggravate aging, and vice versa. Conclusion: According to the findings, ferroptosis may be linked to UVB-induced skin photoaging, which could be attenuated by inhibition of ferroptosis.
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Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC-MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.
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Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Feminino , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Espectrometria de Massas , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismoRESUMO
INTRODUCTION: Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC. OBJECTIVES: We performed whole-exome sequencing in multiple regions of matched primary and metastatic HGSOC specimens to reveal the genetic mechanisms of ovarian tumourigenesis and malignant progression. METHODS: 63 samples (including ovarian carcinoma, omentum metastasis, and normal tissues) were used. We analyzed the genomic heterogeneity, traced the subclone dissemination and establishment history and compared the different genetic characters of cancer evolutionary models in HGSOC. RESULTS: We found that HGSOC had substantial intra-tumour heterogeneity (median 54.2, range 0 â¼ 106.7), high inter-patient heterogeneity (P < 0.001), but relatively limited intra-patient heterogeneity (P = 0.949). Two COSMIC mutational signatures were identified in HGSOCs: signature 3 was related to homologous recombination, and signature 1 was associated with aging. Two scenarios were identified by phylogenetic reconstruction in our study: 3 cases (33.3 %) showed star topology, and the other 6 cases (66.7 %) displayed tree topology. Compared with star topology group, more driver events were identified in tree topology group (P < 0.001), and occurred more frequently in early stage than in late stage of clonal evolution (P < 0.001). Moreover, compared with the star topology group, the tree topology group showed higher rate of intra-tumour heterogeneity (P = 0.045). CONCLUSION: A dualistic classification model was proposed for the classification of HGSOC based on spatial heterogeneity, which may contribute to better managing patients and providing individual treatment for HGSOC patients.
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Carcinoma , Neoplasias Ovarianas , Feminino , Humanos , Filogenia , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário , MutaçãoRESUMO
OBJECTIVE: To study the toll-like receptor 2 (TLR2) Arg753Gln gene polymorphisms of acne patients of Gan-depression induced qi stagnation syndrome and damp-heat in the interior syndrome, thus laying the foundation for genetics studies on its occurrence. METHODS: The distribution and the frequency of allelic genes were studied in 75 acne patients of damp-heat in the interior syndrome, and 87 acne patients with Gan-depression induced qi stagnation syndrome, as well as 70 healthy subjects (as the normal control group) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: There was significant difference in the frequency of the genotype Arg/Gln + Gln/Gln in the TLR2 Arg753Gln genetic polymorphisms [26. 44% (23/87) in Gan-depression induced qi stagnation syndrome, 41.33% (31/75) in damp-heat in the interior syndrome, and 12.86% (9/70) in the normal control group] (P < 0.05). CONCLUSION: The existence of 753Gln allele in the Arg753Gln of TLR2 increased the onset risk of acne patients of Gan-depression induced qi stagnation syndrome and damp-heat in the interior syndrome.
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Acne Vulgar/genética , Polimorfismo Genético , Receptor 2 Toll-Like/genética , Acne Vulgar/diagnóstico , Acne Vulgar/etnologia , Adolescente , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Medicina Tradicional Chinesa , Fenótipo , Qi , Adulto JovemRESUMO
Objective: To probe into the ameliorative effect of Yanghe Decoction on pulmonary injury and immunologic derangement in asthmatic mice. Methods: C57BL/6 mice were randomized into control (Con), Model, and Yanghe Decoction (YHF) groups, with 12 in each. The asthma model of adult female mice was induced by ovalbumin in the Model group, and the YHF group was treated by Yanghe Decoction on the basis of asthma modeling. The Con group received the same amount of normal saline. Inspiratory resistance (Ri), expiratory resistance (Re), lung compliance (CL), and maximal voluntary ventilation (MVV) were measured after modeling. Lung tissue was collected for the measurement of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, and tumor necrosis factor-α (TNF-α) by ELISA kits. Combined with HE staining and PAS staining, the pathological alterations of the lung in each group were observed, and CD4+, Th2, and Th1 contents were determined by flow cytometry (FCM). Results: The pulmonary function (PF) test revealed notably reduced Ri and Re as well as enhanced CL and MVV in asthmatic mice after the application of Yanghe Decoction. Yanghe Decoction dramatically ameliorated the pathological changes of lung tissue in asthmatic mice, as demonstrated by the staining results. ELISA results showed that Yanghe Decoction validly reduces lung tissue IL-4, IL-5, IL-6, IL-13, TNF-α and upregulates IL-10 in asthmatic mice. FCM indicated that Yanghe Decoction obviously reduced the number of Th1 and Th2 cells in asthmatic mice, although it caused the decrease of CD4+ cells, but the difference was not statistically significant. Conclusions: Yanghe Decoction can effectively ameliorate the inflammatory reaction, immune cell disorder, and PF injury in ovalbumin-induced asthmatic mice.
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Asma , Lesão Pulmonar , Animais , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas , Feminino , Interleucina-10/efeitos adversos , Interleucina-13/efeitos adversos , Interleucina-5/efeitos adversos , Interleucina-6/efeitos adversos , Lesão Pulmonar/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/efeitos adversos , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
Although ovarian cancer, a gynecological malignancy, has the highest fatality rate, it still lacks highly specific biomarkers, and the differential diagnosis of ovarian masses remains difficult to determine for gynecologists. Our study aimed to obtain ovarian cancer-specific protein candidates from the circulating small extracellular vesicles (sEVs) and develop a protein panel for ovarian cancer screening and differential diagnosis of ovarian masses. In our study, sEVs derived from the serum of healthy controls and patients with cystadenoma and ovarian cancer were investigated to obtain a cancer-specific proteomic profile. In a discovery cohort, 1119 proteins were identified, and significant differences in the protein profiles of EVs were observed among groups. Then, 23 differentially expressed proteins were assessed using the parallel reaction monitoring in a validation cohort. Through univariate and multivariate logistic regression analyses, a novel model comprising three proteins (fibrinogen gamma gene (FGG), mucin 16 (MUC16), and apolipoprotein (APOA4)) was established to screen patients with ovarian cancer. This model exhibited an area under the receiver operating characteristic curve (AUC) of 0.936 (95% CI, 0.888-0.984) with 92.0% sensitivity and 82.9% specificity. Another panel comprising serum CA125, sEV-APOA4, and sEV-CD5L showed excellent performance (AUC 0.945 (95% CI, 0.890-1.000), sensitivity of 88.0%, specificity of 93.3%, and accuracy of 89.2%) to distinguish malignancy from benign ovarian masses. Altogether, our study provided a proteomic signature of circulating sEVs in ovarian cancer. The diagnostic proteomic panel may complement current clinical diagnostic measures for screening ovarian cancer in the general population and the differential diagnosis of ovarian masses.
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OBJECTIVE: The aim of this study was to use network pharmacology to explore the potential targets and mechanisms of action of Qibao Meiran Dan in relation to delaying skin aging. METHODS: The traditional Chinese medicine systems pharmacology database and analysis platform, and the traditional Chinese medicine integrated database, were used to screen the active ingredients and targets of Qibao Meiran Dan. The human gene database GeneCards and the gene database of the National Center for Biotechnology Information were jointly adopted to obtain skin aging-related target genes. The search tool for the retrieval of interacting genes/proteins (STRING) database was used for core analysis of protein-protein interaction. RESULTS: In total, 72 effective active ingredients, 273 action targets, 234 skin aging target genes, and 64 intersecting core targets were identified. GO enrichment analysis provided 393 biological process entries, and the KEGG analysis was represented by the tumor necrosis factor (TNF) signaling pathway, where the core targets of TNF-α and matrix metalloproteinase-1 (MMP-1) were enriched. The experimental results showed that cell morphology was clearer and more refractive in the Qibao Meiran Dan group than in the model group. CONCLUSION: Qibao Meiran Dan may regulate oxidative stress injury and collagen metabolism by downregulating the expression of TNF-α and MMP-1, thus slowing skin aging.
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Medicamentos de Ervas Chinesas , Envelhecimento da Pele , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 1 da Matriz/genética , Fator de Necrose Tumoral alfa , Farmacologia em RedeRESUMO
Purpose: To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods: First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein-protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results: A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, ß-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion: Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.
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Oxidative stress is one of the most important causes of the cellular senescence process. Previous studies showed that ß-catenin can regulate FoxO3a and this association was enhanced in cells exposed to oxidative stress. It has also been reported that ß-catenin can regulate some senescence-related proteins. We propose that ß-catenin may play a crucial role in senescence of normal human primary skin fibroblasts (NHSFs). Here, we explored the roles and mechanisms of ß-catenin on H(2)O(2)-induced senescence in NHSFs. ß-catenin expression was decreased in NHSFs after H(2)O(2) treatment. Overexpression of ß-catenin in NHSFs led to a marked delay of many senescent phenotypes induced by H(2)O(2). Furthermore, overexpression of ß-catenin in NHSFs can antagonise the alteration of reactive oxygen species accumulation and some senescence-related proteins expression induced by H(2)O(2) treatment. Our data demonstrated that ß-catenin can protect NHSFs from H(2)O(2)-induced premature senescence by alleviating oxidative stress and regulating some senescence-related molecules.
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Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Peróxido de Hidrogênio/toxicidade , Pele/efeitos dos fármacos , Pele/metabolismo , beta Catenina/metabolismo , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Estresse Oxidativo , Pele/patologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/patologiaRESUMO
OBJECTIVE: To study the relationship between the single nucleotide polymorphisms (SNPs) of the human ß-defensin 1-gene (DEFB1) and the genetic susceptibility of acne vulgaris in the Han Chinese ethnic group. METHODS: A total of 104 patients with acne vulgaris and 126 healthy participants were included in our study. We analyzed the association between acne vulgaris and the polymorphisms in the DEFB1 G-52A, C-44G, and G-20A gene. We then analyzed the relationship between the different genotypes and the susceptibility to acne vulgaris. RESULTS: The frequency of DEFB1 C-44G genetic polymorphisms between the acne vulgaris group and the control group was significantly different (P < 0.05). The frequency of DEFB1 G-20A genetic polymorphisms between the acne vulgaris group and the control group was also significantly different (P < 0.05). CONCLUSION: The -44G or -20A allele showed a low expression in acne vulgaris, which has already been shown to correlate with the low risk of acne vulgaris among Chinese Han patients. This further supports the contribution of the DEFB1 gene to the pathogenesis of acne.
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OBJECTIVE: Artesunate, a semi-synthetic derivative of artemisinin, exerts various pharmacological activities. Nevertheless, the effects of Art on skin photoaging remain unclear. Herein, we investigated whether Art ameliorated ultraviolet-irradiated skin photoaging in HaCaT cells and mice. METHODS: To construct skin photoaging cellular models, HaCaT cells were irradiated by UV (UVB, 20mJ/cm2) for 5 days. HaCaT cells were pretreated with three concentrations of Art (1, 5 and 20 µg/ml) for 2 h each day. After 5 days, cell senescence, ROS production, SOD levels, p16INK4a and ß-catenin expression, proliferation and apoptosis were detected in HaCaT cells. Effects of Art on normal cells were investigated. After sh-ß-catenin transfection or XAV-939 treatment, HaCaT cells were pretreated with 20 µg/ml Art and irradiated by UVB. After 5 days, skin photoaging was then observed. Furthermore, skin photoaging mouse models were established and the effects of Art and ß-catenin silencing on skin photoaging were investigated. RESULTS: Art treatment suppressed cell senescence, intracellular ROS production, p16INK4a expression and apoptosis and promoted proliferation and SOD and ß-catenin expression in UVB irradiated HaCaT cells. But Art had no toxic effects on normal cells. Silencing ß-catenin by sh-ß-catenin or XAV-939 exacerbated UVB irradiation-mediated cell senescence, apoptosis, and ROS production in HaCaT cells, which was ameliorated by Art treatment. The therapeutic effects of Art on skin photoaging were also confirmed in mouse models. CONCLUSIONS: These findings suggested that Art treatment alleviated UVB irradiation-driven skin photoaging through enhancing ß-catenin expression, which offered novel clues for pharmacological activity of Art.