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Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10-12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.
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Fibronectinas , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Proteoma , Proteômica , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , BiomarcadoresRESUMO
Few reports of Cryptosporidium spp. in snakes in China have been published. To determine the infection rate and document the presence of Cryptosporidium in pet snakes using molecular methods, 273 fecal samples were collected from eight species of pet snakes from 13 pet households in Beijing, China, and were examined by PCR amplification of the small subunit ribosomal RNA gene. Cryptosporidium was detected from 17 of 273 (6.2%) samples, and nine out of 13 households tested positive for Cryptosporidium with a range of 3.3 to 33.3% among households showing significant difference (p < 0.01). The infection rate of Cryptosporidium for females and males was 6.5% (13/201) and 5.6% (4/72), respectively, showing no significant difference (p > 0.05). Six out of eight pet snake species tested positive for Cryptosporidium with a range of 4.2 to 9.1% among species, showing no significant difference (p > 0.05). Two Cryptosporidium species were identified: Cryptosporidium serpentis in 10 samples and Cryptosporidium varanii in seven samples. No zoonotic Cryptosporidium species occur in our study populations.
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Criptosporidiose/parasitologia , Cryptosporidium/isolamento & purificação , Animais de Estimação/parasitologia , Serpentes/parasitologia , Animais , Pequim , Cryptosporidium/classificação , Cryptosporidium/genética , Fezes/parasitologia , Reação em Cadeia da PolimeraseRESUMO
China has become the world's largest emitter of carbon dioxide, putting significant pressure on the government to reduce emissions. This study analyzes the driving factors of carbon emissions in 281 prefecture-level cities in China from 2003 to 2019, based on carbon emission data matched with the locations of thermal power stations and nighttime light data. Firstly, we compare the accuracy of multivariate linear regression and random forest models, finding that the random forest regression yields superior results. Then, we rank the impact of various factors using the random forest method, revealing that population, economic development, and industrialization are the top three influencing factors. The interaction between population and economic development explains 68.5% of carbon emissions, with regional variations in the ranking of influencing factors. The main policy implications of this study are as follows: firstly, there is no need to overly concern about the impact of population growth on carbon emissions, and policies regarding fertility can be adjusted flexibly; secondly, controlling urbanization to a certain extent is conducive to achieving efficient low-carbon cities; thirdly, during the process of industrialization, carbon emissions inevitably increase, and it is advisable to accelerate industrialization to reach a turning point as soon as possible.
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Background and purpose: Canine mammary tumors are the most common tumor disease of female dogs, and adjuvant chemotherapy often results in multi-drug resistance. Currently, the mechanisms underlying the development of tumor multi-drug resistance are unclear. The translation of research applications that can be used to effectively overcome tumor resistance is similarly hampered. Therefore, it is urgent to construct multi-drug resistance models of canine mammary tumors that can be used for research, to explore the mechanisms and means of overcoming resistance. Materials and methods: In this study, the canine triple negative breast cancer cell line CMT-7364 was induced to develop multidrug resistance using doxorubicin by high-dose drug pulse method. The drug resistance and the expression of drug transport pumps of the cells was verified by CCK8 assay, immunoblotting, qPCR and immunofluorescence. Next, we used scratch assay and Transwell invasion assay to compare the migration and invasion abilities of the two cell lines and examined the expression of EMT-related proteins in both using immunoblotting. The differences of transcriptome between parental and drug-resistant cell lines were detected by RNA-seq sequencing. Finally, mouse xenograft models of drug-resistant and parental cell lines were constructed to evaluate the tumorigenic ability. Results: After more than 50 generations of continuous passages stimulated by high-dose drug pulse method, the morphology of drug-resistant cell line CMT-7364/R tended to be mesenchymal-like and heterogeneous under light microscopy compared with the parental cell line CMT-7364/S, and developed resistance to doxorubicin and other commonly used chemotherapeutic drugs. In CMT-7364/R, BCRP was expressed at higher levels at both transcriptional and protein levels, while P-glycoprotein was not significantly different. Secondly, the migration and invasion ability of CMT-7364/R was significantly enhanced, with decreased expression of E-cadherin and increased expression of vimentin and mucin 1-N terminus. Finally, mouse xenograft models were constructed, while there was no significant difference in the volume of masses formed at 21 days. Conclusion: In summary, by using the canine mammary tumor cell line CMT-7364/S as the parental cell line, we successfully constructed a multidrug-resistant CMT-7364/R with high-dose drug pulse methods. Compared to its parental cell line, CMT-7364/R has decreased growth rate, overexpression of BCRP and increased migration and invasion ability due to EMT. The results of this study showed that CMT-7364/R might serve as a model for future studies on tumor drug resistance.
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BACKGROUND: Canine inflammatory mammary carcinoma (CIMC) has a high incidence of metastasis, high lethality, and poor prognosis, which needs novel adjuvant agents. Tetramethylpyrazine-Rhein Derivative (TRD) has been shown to have antitumor activity, which is a potential research direction for CIMC. PURPOSE: This study evaluated the efficacy of TRD on CIMC in vitro and in vivo, and provided possibilities for the application of active compounds in traditional Chinese medicine. METHODS: In vitro, TRD cytotoxicity was measured with CCK-8. Flow cytometry and transmission electron microscope were used to detect the cell cycle, cell death, and changes in mitochondria. Wound-healing assay, cell invasion assay, and scanning electron microscope were used to evaluate the suppression of cell migration and invasion. Expression changes were detected by RT-qPCR and western blot assay. In vivo, the lung metastasis models were randomly divided into control, low-dose TRD, high-dose TRD, and positive groups. Each group was administered orally once a day for 18 days and took in vivo imaging photos. RESULTS: The IC50 of TRD in CHMp and MDCK were 42.59 and 79.37 µM, respectively. TRD mediated cell apoptosis by mitochondrial damage and caused S and G2/M phase arrest by downregulating cyclin B1. Moreover, TRD reduced filopodia and inhibited cell migration by downregulating cadherins. In CIMC lung metastasis models, TRD could effectively inhibit tumor growth (P < 0.001) in the lungs without significant toxicity. CONCLUSION: TRD showed potential activity to inhibit CIMC lung metastasis with multi-target and low toxicity.
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Carcinoma , Neoplasias Pulmonares , Animais , Cães , Caderinas/metabolismo , Regulação para Baixo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de CélulasRESUMO
Colorectal cancer (CRC) in dogs has been shown to have similar molecular characteristics to human colorectal cancer. Although researchers have explored the pathogenesis and immune status of human CRC, the canine CRC has been far less studied. As a result, we analyzed canine colorectal tumors and normal canine intestinal samples by Gene Set Enrichment Analysis (GSEA) and found significant enrichment of immune-related pathways, including the TNF-α signaling pathway and IL6-STAT3 signaling pathway. In addition, the differential infiltration of naive B cells and regulatory T cells suggested that canine CRC was in a state of immunosuppression. Weighted gene co-expression network analysis (WGCNA) revealed the gene modules that contribute to differences in regulatory T cell inetfiltration, Further cross-validation of canine and human CRC differential genes obtained three core genes that are both species-conserved and differentially expressed, CD44, NAT10, and ETV4, of which NAT10 and ETV4 have been little studied in the immune status of colorectal cancer. Our findings may have implications for the pathogenesis and progression of CRC in dogs and could be a new potential therapeutic target for CMT and provide a bioinformatics foundation for later clinical experiment validation.
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Neoplasias Colorretais , Doenças do Cão , Humanos , Animais , Cães , Transcriptoma , Fator de Necrose Tumoral alfa , Linfócitos B , Biomarcadores , Neoplasias Colorretais/genética , Neoplasias Colorretais/veterinária , Doenças do Cão/genéticaRESUMO
The concept of adenoma-to-cancer transformation in human colorectal cancer (CRC) is widely accepted. However, the relationship between transcriptome features and adenoma to carcinoma transformation in canines is not clear. We collected transcriptome data from 8 normal colon tissues, 4 adenoma tissues, and 15 cancer tissues. Differential analysis was unable to determine the dynamic changes of genes but revealed that PFKFB3 may play a key role in this process. Enrichment analysis explained metabolic dysregulation, immunosuppression, and typical cancer pathways in canine colorectal tumors. MFuzz generated specific dynamic expression patterns of five differentially expressed genes (DEGs). Weighted correlation network analysis showed that DEGs in cluster 3 were associated with malignant tissues, revealing the key role of inflammatory and immune pathways in canine CRC, and the S100A protein family was also found to be involved in the malignant transformation of canine colorectal tumors. By comparing strategies between humans and dogs, we found five novel markers that may be drivers of CRC. Among them, GTBP4 showed excellent diagnostic and prognostic ability. This study was the first systematic exploration of transformation in canine CRC, complemented the molecular characteristics of the development and progression of canine CRC, and provided new potential biomarkers and comparative oncologic evidence for biomarker studies in human colorectal cancer.
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Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.
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BACKGROUND: Atherosclerosis (AS), the main pathological basis of life-threatening cardiovascular disease, is essentially caused by chronic macrophage inflammation. Overexpression of proline/serine-rich coiled-coil protein 1 (PSRC1) reduces macrophage inflammatory responses and delays AS development. However, the exact mechanism of PSRC1 is unclear. METHODS: Proteins interacting with PSRC1 were screened by proteomics in RAW264.7 cells, followed by RT-qPCR, immunoprecipitation and immunofluorescence to explore the specific mechanistic pathways affecting inflammation. CRISPR-Cas9 constructs for PSRC1-/- ApoE-/- (DKO) mice and high-fat diet-fed ApoE-/- and DKO mice were used for AS models for in vivo experiments. Upstream transcription factors of PSRC1 were predicted by ATAC-seq, ChIP-seq and UCSC, and the regulatory mechanism was verified by ChIP-qPCR and dual luciferase assays. Peripheral blood serum and monocytes were collected from coronary artery disease (CAD) patients and non-CAD patients. RESULTS: Increased binding of ANXA2 to PSRC1 in macrophages under oxidized low-density lipoprotein stimulation and decreased release of ANXA2 to the extracellular compartment were observed. Knockdown of ANXA2 in AS model mice delayed AS progression. Knockdown of ANXA2 in DKO mice reversed the AS-promoting effect of PSRC1 knockdown. Mechanistically, ANXA2 promotes STAT3 phosphorylation, which in turn promotes inflammatory responses. In addition, SP1 is a PSRC1 upstream repressive transcription factor, and the SP1 inhibitor mithramycin (Mith) elevated PSRC1 expression and exerted anti-AS effects in AS model mice. Patients with CAD had considerably greater serum levels of ANXA2 than those without CAD, and Mith reduced the secretion of ANXA2 in peripheral blood monocytes of CAD patients. CONCLUSION: In macrophages, PSRC1 can interact with ANXA2 to inhibit its extracellular release and delay AS development. SP1 is an upstream transcription factor of PSRC1 and inhibits the transcription of PSRC1. The SP1 inhibitor Mith can elevate PSRC1 levels and slow AS progression while reducing ANXA2 release from monocytes in CAD patients. Mith is expected to be a new agent for AS treatment.
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Anexina A2 , Aterosclerose , Doença da Artéria Coronariana , Fosfoproteínas , Animais , Camundongos , Aterosclerose/metabolismo , Inflamação , Macrófagos/metabolismo , Prolina , Serina , Fatores de Transcrição/metabolismo , Fosfoproteínas/metabolismo , Camundongos Knockout para ApoERESUMO
As the fierce battle with cancer is now expanding to companion animals, effective treatment of canine mammary carcinomas (CMT), as the most frequently diagnosed tumor in intact dogs, is becoming a crucial issue. Although many studies have been carried out concerning the clinical application of mammary tumor biomarkers, no ideal biomarker has yet been identified in CMT. Therefore, in this work, we develop EDIL3 as a CMT biomarker having significantly higher expression levels in CMT samples compared to those in controls in GSE13754, GSE22516 and GSE25586 datasets, which suggest that EDIL3 is a gene related to tumorigenesis. We also validate the significantly high expression levels of EDIL3 in CMT samples using our sequencing canine samples. ROC curves analysis showed that in comparison with HER2 reported as predictive factor for CMT patients, EDIL3 exhibits stronger power for CMT recognizing. Moreover, we also find that low expression levels of EDIL3 are associated with advanced grade status in CMT, which indicate a negative correlation between EDIL3 and CMT development. GSEA is employed to unveil the underlying mechanism of this interesting function of EDIL3 in CMT development, and it suggests that the expression level of EDIL3 is related to immunity pathway. Finally, CIBERSORT analysis is employed in this study in order to further explore the relationship between EDIL3 and immunity in CMT, and it unveils that EDIL3 has stably positive correlation with follicular helper T cells and negative correlation with NK resting cells in CMT. Our study develops EDIL3 as a biomarker for assisting CMT distinction, highlighting the relationship of EDIL3 with the infiltrations of follicular helper T cells and NK resting cells, which could be a new potential therapy target for CMT and provide bioinformatics basis for later clinical experiment validation.
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Carcinoma , Doenças do Cão , Neoplasias Mamárias Animais , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/veterinária , Biologia Computacional , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/metabolismo , Cães , Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/genéticaRESUMO
The relationship between narcissism and creativity has inspired interesting debates for decades. Drawing on a new perspective, the current study tried to explain how narcissism influences others' creativity evaluation in the organizational context. Based on the theory of impression management, we suggested that narcissism and creativity may have a more complex relationship rather than a simple linear link. To test this relationship, we conducted a survey of 596 subordinates and 60 leaders in three high-technology companies. The result showed that there was an inverted U-shaped relationship between narcissism and creativity evaluation. Moreover, personal reputation mediated this curvilinear relationship and this relationship was significant only when narcissists were low in political skill. Theoretical and practical implications, limitations and future directions have also been discussed.
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The damage of air pollution to cultural heritage is widely known. However, the quantitative effects still need to be explored at a holistic level. Different from existing research which focuses on the "model calculation" methods, this paper uses an econometric approach to assess the overall impact of air pollution on the sustainable protection of world cultural heritage in China. Based on the data of the annual monitoring report from 2014 to 2020 released by the China World Cultural Heritage Monitoring Platform, this paper uses the thermal inversion as an instrument variable of air pollution to estimate the overall effects of air pollution on all world cultural heritage sites in China. The results indicate that almost all the air pollutants (except for CO) have significantly negative effects on heritage. The damaging effects of gaseous pollutants including SO2, NO2 and O3 is greater than that of particulate pollutants such as PM2.5 and PM10. Rainfall can exacerbate the worsening effects of gaseous pollutants, but will mitigate the negative effects of particulate pollutants; the windy weather may weaken the negative impact. In addition, environmental regulations from the local government can also alleviate the negative influence of air pollution on heritage protection. This research can provide a more comprehensive environmental prevention policy reference for the protection of world cultural heritage.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Monitoramento Ambiental , Gases , Material Particulado/análise , Tempo (Meteorologia)RESUMO
S4A ((1R,2R,3S)-1,2-propanediol acetal-zeylenone) is one of the derivatives of zeylenone and exhibits superior cytotoxicity against the canine breast cancer cell line CIPp. However, its poor aqueous solubility and toxicity to normal tissue limit its clinical application. Therefore, in order to enhance the anticancer effect of S4A, in this article, BSA/BSA-Au-nanocluster-aggregated core/shell nanoparticles (B-BANC-NPs) were prepared by using bovine serum albumin (BSA) and HAuCl4, and then we further synthesized S4A-BSA-Au NPs which were spherical, with a diameter of about 60 nm. In vitro cytotoxicity assessed by using CCK-8 assay demonstrated that the IC50 value of the S4A-BSA-Au NPs was 10.39 µg mL-1, which was not significantly different from that of S4A (10.45 µg mL-1). In vitro apoptosis assay showed that the apoptosis rate of cells treated with S4A-BSA-Au NPs was 20.12%, which was significantly higher than that of the control group treated with S4A (11.3%). Notably, S4A-BSA-Au NPs were shown to effectively accumulate at tumor sites with fluorescence tracing. Besides, the effect of S4A-BSA-Au NPs on SPARC expression was determined by western blotting, and the result showed that 24 h after applying S4A-BSA-Au NPs, SPARC expression in low, middle and high dosage groups was lower than that of the control group, and the tendency showed dose dependence. The results revealed that S4A-BSA-Au NPs could effectively improve the anti-tumor activity of S4A on canine breast cancer, which may be associated with their abilities to effectively accumulate within tumor and to reduce the expression of SPARC.
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In recent years, the Chinese government has issued a series of deepening reform policies around smart healthcare, established a diversified technical basis and environmental protection, and deeply excavated the derivative value of healthcare information, aiming to provide high-quality healthcare services for patients. Information interaction in the context of smart healthcare is a kind of health information interaction completed by users with smart healthcare applications as the hub. It is an application form of social behavior and has an impact on value cocreation. Based on the theory of information interaction and value cocreation, this paper systematically reviews the research on information interaction and value cocreation in the smart healthcare context, analyzes the information interaction mode and information interaction mechanism in the smart healthcare context, constructs a theoretical model of the impact of information interaction on value cocreation, and empirically tests the relationship between information interaction and value cocreation in the smart healthcare context. The research of this paper aims to provide high-quality information interaction services for smart healthcare users, promote the dimensional management of information behavior in the context of smart healthcare, and promote the continuous improvement of the operation and management of smart healthcare.
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Atenção à Saúde , Serviços de Saúde , Instalações de Saúde , HumanosRESUMO
Colon cancer is one of the deadliest tumors in the world, and with high metastasis rate and mortality, effective drugs for its treatment are still in need. Auranofin (AF) is a gold complex that has been attested by FDA for treating human rheumatism, and researchers have found that AF acts as a great antitumor drug in recent years. ICG-001 is a small molecule inhibitor of Wnt/ß-catenin pathway. In the present study, we aimed to explore the synergistic antitumor effects and the underlying mechanisms of AF and ICG-001 combination therapy on human colon cancer. The results showed that AF and ICG-001 synergistically depressed the growth and invasion of human colon cancer cells by inhibiting the phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) and its downstream mediator B-cell lymphoma-2-like 1 (Bcl-xL) and inducing caspase-3-dependent apoptosis. Moreover, AF combined with ICG-001 synergistically inhibited the growth of colon cancer in subcutaneous xenograft mice models and restrained metastasis in lung metastasis mice models. In conclusion, our results demonstrated that combination of AF and ICG-001 suppressed the proliferation and metastasis of colon cancer by inhibiting STAT3 phosphorylation. Therefore, this combination therapy may possess potential therapeutic properties for human colon cancer.
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Canine breast cancer (CBC) is the most common spontaneous tumor in intact female dogs, especially in developing countries. The effective anti-tumor agents or therapies for the clinical treatment of CBC are still in need. Auranofin (AF) is a gold complex that has been attested by FDA for treating human rheumatism, which has been found as a great anti-tumor agent in recent years. ICG-001 is a small molecule inhibitor of Wnt/ß-catenin pathway. In the present study, we demonstrated that a combination of AF and ICG-001 could synergistically suppress the proliferation of CBC in vitro and in vivo. Moreover, the synergistical effect was related with apoptosis caused by mitochondrial damage and ROS production. In conclusion, combination of AF and ICG-001 could synergistically suppress the growth of CBC in vitro and in vivo by leading apoptosis via mitochondrial signaling pathway and might provide a novel potential choice for the clinical treatment of CBC.
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OBJECTIVE: To analyze the correlation of annexin A2 with coronary atherosclerotic heart disease (CAD) and the severity of CAD. METHODS: We collected data from a total of 200 inpatients admitted in our department between August, 2017 and August, 2019. According to the. RESULTS: of coronary angiography, the patients were divided into CAD group (n=150) and non-CAD (n=50), and the CAD patients was further divided, according to their clinical stability, into stable angina (SAP) group and acute coronary syndrome (ACS) group. Serum levels of annexin A2, MPO and PON1 were detected in all these patients, and their correlations with CAD, disease severity, and degree of coronary artery stenosis were analyzed.ResultsThe levels of annexin A2 and MPO were significantly higher in CAD patients than in non-CAD patients (P < 0.05). Among the CAD patients, those with ACS had significantly higher levels of annexin A2 (P < 0.05) and lower levels of PON-1 (P < 0.05) than those with SAP, but annexin A2 level was not significantly correlated with coronary lesion count, Gensini score, or the co-morbidity of diabetes. CONCLUSIONS: Annexin A2 is significantly elevated in patients with CAD, especially in those with ACS, and can be used as a predictor of clinical instability.
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Anexina A2/sangue , Doença da Artéria Coronariana , Arildialquilfosfatase , Biomarcadores , Angiografia Coronária , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.
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Little is known regarding the Enterocytozoon bieneusi genotypes in snakes worldwide. In the present study, a total of 273 fecal samples were collected from pet snakes in Beijing, China. They were then tested for the presence of E. bieneusi by PCR amplification of the internal transcribed spacer (ITS) gene. The overall infection rate of E. bieneusi was 4.4% (12/273), with the highest infection rate (20%, 1/5) of E. bieneusi was found in the Black rat snake (Pantherophis obsoletus), whereas no positive samples were detected from both Milk (0/22) and Coast garter snakes (0/2). Eight genotypes were identified, including four known genotypes: EbpA (n = 1), EbpC (n = 5), Henan-III (n = 1), and SHR1 (n = 1), and four novel genotypes: CRep-5 (n = 1), CRep-6 (n = 1), CRep-7 (n = 1), and CRep-8 (n = 1). Among them, EbpC (41.7%, 5/12) was the predominant genotype. Phylogenetic analysis showed that seven genotypes belonged to group 1, while genotype SHR1 belonged to group 2. Genotypes EbpA, EbpC, and Henan-III have been previously reported in humans. This suggests that pet snakes are a potential source of zoonotic microsporidiosis transmission in China.
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BACKGROUND: Catechins, polyphenols derived from tea leaves, have been shown to have antibacterial properties, through direct killing of bacteria as well as through inhibition of bacterial toxin activity. In particular, certain catechins have been shown to have bactericidal effects on the oral bacterium, Aggregatibacter actinomycetemcomitans, as well as the ability to inhibit a key virulence factor of this organism, leukotoxin (LtxA). The mechanism of catechin-mediated inhibition of LtxA has not been shown. METHODS: In this work, we studied the ability of six catechins to inhibit LtxA-mediated cytotoxicity in human white blood cells, using Trypan blue staining, and investigated the mechanism of action using a combination of techniques, including fluorescence and circular dichroism spectroscopy, confocal microscopy, and surface plasmon resonance. RESULTS: We found that all the catechins except (-)-catechin inhibited the activity of this protein, with the galloylated catechins having the strongest effect. Pre-incubation of the toxin with the catechins increased the inhibitory action, indicating that the catechins act on the protein, rather than the cell. The secondary structure of LtxA was dramatically altered in the presence of catechin, which resulted in an inhibition of toxin binding to cholesterol, an important initial step in the cytotoxic mechanism of the toxin. CONCLUSIONS: These results demonstrate that the catechins inhibit LtxA activity by altering its structure to prevent interaction with specific molecules present on the host cell surface. GENERAL SIGNIFICANCE: Galloylated catechins modify protein toxin structure, inhibiting the toxin from binding to the requisite molecules on the host cell surface.