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Compound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of the EGFR tyrosine kinase domain (TKD), in which an EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compound EGFR mutation shows poor clinical response to EGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor had EGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present an EGFR exon21 L858R/A871G mutation patient exerted significant benefit to icotinib, another first-generation EGFR-TKI, indicating that different EGFR-TKIs have diversiform sensitive sites and therapeutic effects, consistent mutation sites might achieve heterogeneous benefits from different EGFR-TKIs. Our case report provides promising EGFR-TKI for clinical treatment with EGFR exon21 L858R/A871G mutation in NSCLC. More dedicated efforts are needed to clarify their biologic effects on disease course and drug responsiveness.
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Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Éteres de Coroa , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , QuinazolinasRESUMO
BACKGROUND: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. AIMS: To describe the clinical features of H7N9 avian influenza and the response to treatment. METHODS: Clinical, radiological and histopathological data, and treatment-related of H7N9-infected patients hospitalised during 2014-2017 were extracted and analysed. RESULTS: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C interferon-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype. CONCLUSIONS: H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness.
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Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Pneumonia , Adulto , Idoso , China , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Proteínas de Membrana , Pessoa de Meia-Idade , Pneumonia/virologia , Proteínas de Ligação a RNA , Estudos RetrospectivosRESUMO
Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.
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Moléculas de Adesão Celular/fisiologia , Estresse Fisiológico , Estresse Psicológico , Sinapses , Adesão Celular , Humanos , Plasticidade NeuronalRESUMO
[This corrects the article DOI: 10.1016/j.fochx.2024.101239.].
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Objective: To investigate public awareness about core information regarding chronic diseases and identify factors influencing that awareness among Anhui Province residents, provide a scientific basis for policy-making, and formulate corresponding intervention measures. Methods: From March to April 2021, 12 provincial-level representative counties and districts of Anhui province in the China Adult Chronic Disease and Nutrition Surveillance were selected as survey sites, and 4790 residents were recruited for the survey using stratified multi-stage cluster random sampling. Basic details about the study participants were collected and their awareness of core information about major chronic diseases was measured through an online survey using WeChat. Results: In 2021, the awareness rate of core information about chronic diseases among residents of Anhui Province was 54.93%. Multivariate logistic regression analysis showed that a higher awareness rate was associated with the following factors: non-housework occupations (agriculture, forestry, animal husbandry, and fishery: OR = 1.309, commercial services and production and transportation: OR = 1.450, institutions, and professional and technical personnel: OR = 1.461), a high education level (high school/junior high school/technical school OR = 1.357, college and above OR = 2.133), and residence in the southern and northern Anhui areas (southern Anhui OR = 1.282, northern Anhui OR = 1.431); whereas in rural areas (by district and country) (OR = 0.863), the awareness rate was low (all P < 0.05). Conclusions: The awareness rate of core information about chronic diseases among residents of Anhui, China, is low. It is necessary to strengthen awareness about chronic disease prevention and management by targeting specific groups of people in this region.
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OBJECTIVE: Rheumatoid arthritis (RA) may cause damage to multiple organs and may further restrict the patient's physical, psychological and social functions. This meta-analysis aimed to explore the prevalence of frailty and prefrailty and the influential factors in RA patients. METHODS: PubMed, Web of Science, Cochrane, Embase, and CNKI were searched to identify related articles. Articles published before July 23rd, 2021 that assessed frailty in patients with RA qualified for the systematic review and meta-analysis. A quality appraisal of the studies was performed using the Agency for Healthcare Research and Quality and Newcastle-Ottawa Scales. The pooled results were displayed as odds ratios or standardized mean differences (ORs/SMDs) and 95% confidence intervals (CIs). RESULTS: The article search generated 2273 articles, of which 16 satisfied the inclusion criteria and were merged in the final review. A total of 8556 RA patients were finally included. The pooled prevalence of frailty in the patients with RA was 33.5% (95% CI: 25.2-41.7%), and the pooled prevalence of prefrailty was 39.9% (95% CI: 29.4-50.3%). Subgroup analyses showed that frailty was more prevalent in females (24.7%) than in males (19.1%). The prevalence of prefrailty in females was similar to that in males among the RA patients. Frailty in RA was associated with the female sex (OR: 1.47, 95% CI: 1.04-2.07) and disease activity (OR: 1.47, 95% CI: 1.03-2.09). CONCLUSION: Frailty is prevalent in RA patients. Female gender and disease activity are associated with the prevalence of frailty in RA patients.
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Artrite Reumatoide , Fragilidade , Artrite Reumatoide/epidemiologia , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Masculino , PrevalênciaRESUMO
OBJECTIVE: To evaluate the reliability and validity of the Chinese version of the eight-item Morisky Medication Adherence Scale (MMAS-8) in Chinese patients with systemic lupus erythematosus (SLE). METHODS: The survey was conducted with a consecutive sampling of 158 Chinese SLE patients attending public hospitals from January to March 2021. We used the translated Chinese version of the MMAS-8 to collect related data. Reliability, item, and factor analyses were used to test the reliability and validity of the MMAS-8 scale in the selected patients. The internal consistency reliability was evaluated using Cronbach's α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 30 participants. Construct validity was evaluated using confirmatory factor analysis and correlations between the Self-efficacy for Appropriate Medication Use Scale (SEAMS) and related measures. RESULTS: The internal consistency reliability of the Chinese version of the MMAS-8 was high (Cronbach's α = 0.817), and the test-retest reliability was excellent (intraclass correlation = 0.947; P < 0.001). There were significant differences in the F test and t test between the two extreme groups before and after the ranking of 27% of the questionnaire scores (P < 0.001). The Kaiser-Meyer-Olkin (KMO) value of construct validity was 0.860. The spherical test value of Bartlettgers was 417.8822. Factor analysis yielded three components that accounted for 69.375% of the total variance. Exploratory factor analysis identified three dimensions of the Chinese version of the MMAS-8. In terms of criterion validity, the correlation of the MMAS-8 score in SEAMS indicated that the convergent validity was good (r = 0.926; P < 0.001). CONCLUSIONS: This study shows that the Chinese version of the Medication Adherence Scale-8 is a reliable and valid tool for assessing medication adherence in Chinese SLE patients. Key Points ⢠Many factors affect medication adherence in SLE patients. ⢠Many questionnaires measure medication adherence levels. ⢠There is a lack of reliable validation of medication adherence questionnaires specifically for SLE patients.
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Lúpus Eritematoso Sistêmico , Adesão à Medicação , China , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.
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Distúrbios do Sono por Sonolência Excessiva , Lúpus Eritematoso Sistêmico , Distúrbios do Início e da Manutenção do Sono , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/genética , Análise da Randomização Mendeliana , Sono/genéticaRESUMO
In this paper, new supramolecular extractants, which contained surfactant, alkane and alkanol, were designed and used to separate PQQ. After a series of tests, the optimal extractant composition was determined as benzalkalonium (C8-C16) chloride (BC): n-hexane:n-pentanol, and the highest extraction rate could reach 98%. The extraction equilibrium could be reached in five minutes. The mechanism of the extraction selectivity was inferred as an ion-pair and π-π complexation interaction between PQQ and BC, which was indicated by UV and fluorescence quenching experiments. To recycle the organic extractant, the extract was back-extracted with sodium chloride solution. After extraction, back extraction and crystallization, an isolated product with a purity of 97.5% was obtained from G. oxydans fermentation broth. The product was identified as PQQ by HPLC analysis and MS. Above all, the present research developed a simple and efficient method for the separation of PQQ from fermentation broth.
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Gluconobacter oxydans/enzimologia , Cofator PQQ/isolamento & purificação , Compostos de Benzalcônio/química , Cromatografia Líquida de Alta Pressão , Fermentação , Gluconobacter oxydans/química , Hexanos/química , Espectrometria de Massas , Pentanóis , SolventesRESUMO
Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion.
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Ansiedade/fisiopatologia , Giro Denteado/fisiopatologia , Memória/fisiologia , Tato/fisiologia , Animais , Comportamento Animal/fisiologia , Espinhas Dendríticas/fisiologia , Córtex Entorrinal/fisiopatologia , Feminino , Integrases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , Fatores de TempoRESUMO
BACKGROUND: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. METHODS: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. RESULTS: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. CONCLUSION: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Transcrição Ikaros/metabolismo , MicroRNAs/metabolismo , Derrame Pleural Maligno/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Citometria de Fluxo , Humanos , Fator de Transcrição Ikaros/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Derrame Pleural Maligno/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Chronic bronchitis and emphysema are pathologic features of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced endoplasmic reticulum (ER) stress has been implicated in the COPD development, but the molecular mechanism by which it contributes to COPD etiology and the specific role it plays in COPD pathogenesis remain poorly understood. Here, we aimed to determine the role of ER stress in the pathogenesis of CS-induced airway inflammation and emphysema. Exposure to CS significantly increased the expression of ER stress markers in Beas-2B cells and in mouse lungs, possibly through the production of oxidative stress. Further, inhibition of ER stress by 4-phenylbutyric acid (4-PBA) reduced CS extract-induced inflammation in Beas-2B cells through the modulation of NF-κB signaling. 4-PBA also protected against CS-induced airway inflammation and the development of emphysema in mice, which was associated with a reduction in NF-κB activation and alveolar cell apoptosis in the lungs. Taken together, our results suggest that ER stress is crucial for CS-induced inflammation and emphysema, and that targeting ER stress may represent a novel approach to the treatment of COPD.
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We aimed to investigate whether vitamin D levels affect the expression of autophagy related genes (Atgs) and the counts of T-cell subsets in active systemic lupus erythematosus (SLE), as well as to assess the association between Atgs and T-cell subsets. Serum levels of 25(OH)D3, Atgs and T-cell subsets were measured in 50 patients with active SLE. Serum 25(OH)D3 levels <10 ng/ml and 10-30 ng/ml were defined as severe vitamin D deficiency and vitamin D insufficiency, respectively. Comparisons were made between values of severe vitamin D deficiency and vitamin D insufficiency patients, and the correlations between Atgs in PBMCs and T-cell subsets were carried out. mTOR mRNA levels were higher (P=0.036) and LC3 mRNA levels were lower (P<0.001) in severe vitamin D deficiency group compared to vitamin D insufficiency group. The counts of CD4+ T cells and the CD4/CD8 ratio were significantly higher in severe vitamin D deficiency group compared to vitamin D insufficiency group (P=0.001, P<0.001,respectively). LC3 mRNA levels correlated negatively with CD4+ T cells counts (r=-0.302, P=0.033), while correlated positively with CD8+ T cells counts (r=0.299, P=0.035). Serum 25(OH)D3 levels correlated negatively with the counts of CD4+ T cells (r=-0.423, P=0.002) and correlated positively with the counts of CD8+ T cells (r=0.318, P=0.024). Our results suggested that severe vitamin D deficiency affected the expression of Atgs in PBMCs and T-cell subsets in active SLE, indicating that vitamin D may affect T-cell subsets via regulating autophagy.
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Microporous carbon polyhedrons (MCPs) are encapsulated into polyacrylonitrile (PAN) nanofibers by electrospinning the mixture of MCPs and PAN. Subsequently, the as-prepared MCPs-PAN nanofibers are employed as sulfur immobilizer for lithium-sulfur battery. Here, the S/MCPs-PAN multicomposites integrate the advantage of sulfur/microporous carbon and sulfurized PAN. Specifically, with large pore volume, MCPs inside PAN nanofibers provide a sufficient sulfur loading. While PAN-based nanofibers offer a conductive path and matrix. Therefore, the electrochemical performance is significantly improved for the S/MCPs-PAN multicomposite with a suitable sulfur content in carbonate-based electrolyte. At the current density of 160 mA g-1sulfur, the S/MPCPs-PAN composite delivers a large discharge capacity of 789.7 mAh g-1composite, high Coulombic efficiency of about 100% except in the first cycle, and good capacity retention after 200 cycles. In particular, even at 4 C rate, the S/MCPs-PAN composite can still release the discharge capacity of 370 mAh g-1composite. On the contrary, the formation of the thick SEI layer on the surface of nanofibers with a high sulfur content are observed, which is responsible for the quick capacity deterioration of the sulfur-based composite in carbonate-based electrolyte. This design of the S/MCPs-PAN multicomposite is helpful for the fabrication of stable Li-S battery.
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To determine the expression of mTOR, Becline-1, LC3 and p62 in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) and assess their relationship with disease activity and immunologic features. The expression of mTOR, Becline-1, LC3 and p62 was detected by RT-PCR in 81 SLE subjects and 86 age- and sex-matched healthy controls. Data regarding demographics and clinical parameters were collected. Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score. Independent sample t-test was used to analyze the expression of mTOR, Becline-1, LC3, and p62 in the two groups. Pearson's or Spearman's correlation was performed to analyze their relationship with disease activity and immunologic features. The mean levels of Becline-1, LC3 and p62 mRNA were significantly higher in SLE patients than the controls (9.96×10-4 vs 7.38×10-4 for Becline-1 with P<0.001; 4.04×10-5 vs 2.62×10-5 for LC3 with P<0.001; 9.51×10-4 vs 7.59×10-4 for p62 with P=0.008). However, the levels of mTOR mRNA in SLE patients were not significantly different from that in controls. Correlation analysis showed that Becline-1, LC3 and p62 mRNA levels correlated positively with SLEDAI, IgG and ds-DNA, negatively with C3. Our results suggested that autophagosomes formation were activated and their degradation were blocked in SLE. Moreover, the maintenance of autophagy balance can improve disease activity and immune disorders in SLE patients.
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Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer (GC), MACC1 has been shown to be involved in oncogenesis and tumor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelial-to-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry (VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.
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Neoplasias Gástricas/etiologia , Fatores de Transcrição/fisiologia , Epigênese Genética , Transição Epitelial-Mesenquimal , Humanos , Linfangiogênese , Proteínas Proto-Oncogênicas c-met/fisiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Transativadores , Fatores de Transcrição/sangue , Fatores de Transcrição/genética , Microambiente TumoralAssuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas RGS , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , DNA Intergênico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Toad venom and toad skin have been widely used for treating various cancers in China. Bufadienolides are regarded as the main anticancer components of toad venom, but the difference on composition and anticancer activities of bufadienolides between toad venom and toad skin remains unclear. METHODS: Fractions enriched with free and conjugated bufadienolides were prepared from toad venom and toad skin. Bufadienolides in each fraction were comprehensively profiled by using a versatile UHPLC-TOF-MS method. Relative contents of major bufadienolides were determined by using three bufogenins and one bufotoxin as marker compounds with validated UHPLC-TOF-MS method. Furthermore, cytotoxicity of the fractions was examined by MTT assay. RESULTS: Two fractions, i.e., bufogenin and bufotoxin fractions (TV-F and TV-C) were isolated from toad venom, and one bufotoxin fraction (TS-C) was isolated from toad skin. Totally 56 bufadienolides in these three fractions were identified, and 29 were quantified or semi-quantified. Bufotoxins were identified in both toad venom and toad skin, whereas bufogenins exist only in toad venom. Bufalin-3-conjugated bufotoxins are major components in toad venom, whereas cinobufotalin and cinobufagin-3-conjugated bufotoxins are main bufotoxins in toad skin. MTT assay revealed potent cytotoxicity of all the fractions in an order of TV-F>TV-C>TS-C. CONCLUSIONS: Our study represents the most comprehensive investigation on the chemical profiles of toad venom and toad skin from both qualitative and quantitative aspects. Eight bufotoxins were identified in toad skin responsible for the cytotoxicity for the first time. Our research provides valuable chemical evidence for the appropriate processing method, quality control and rational exploration of toad skin and toad venom for the development of anticancer medicines.
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Venenos de Anfíbios/química , Antineoplásicos/isolamento & purificação , Bufanolídeos/isolamento & purificação , Pele/química , Animais , Antineoplásicos/farmacologia , Bufanolídeos/farmacologia , Bufo bufo , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Células Hep G2 , Humanos , Células MCF-7 , Espectrometria de MassasRESUMO
We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P < 0.001) and high body mass index (BMI) (OR 1.88, P < 0.001). However, the seniors were less likely to have vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients.
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Principal component analysis (PCA) and cluster analysis (CA) are utilized to identify the effects caused by human activities on water quality along the coast of Sanya, South China Sea. PCA and CA identify the seasonality of water quality (dry and wet seasons) and polluted status (polluted area). The seasonality of water quality is related to climate change and Southeast monsoons. Spatial pattern is mainly related to anthropogenic activities (especially land input of pollutions). PCA reveals the characteristics underlying the generation of coastal water quality. The temporal and spatial variation of the trophic status along the coast of Sanya is governed by hydrodynamics and human activities. The results provide a novel typological understanding of seasonal trophic status in a shallow, tropical, open marine bay.