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Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in certain human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.
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Adenocarcinoma , Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Proteína Ligando Fas , ARN Largo no Codificante/metabolismoRESUMEN
Small extracellular vesicles (sEVs) are essential mediators of intercellular communication within the tumor microenvironment (TME). Although the biological features of sEVs have been characterized based on in vitro culture models, recent evidence indicates significant differences between sEVs derived from tissue and those derived from in vitro models in terms of both content and biological function. However, comprehensive comparisons and functional analyses are still limited. Here, we collected sEVs from breast cancer tissues (T-sEVs), paired normal tissues (N-sEVs), corresponding plasma (B-sEVs), and tumor organoids (O-sEVs) to characterize their transcriptomic and proteomic profiles. We identified the actual cancer-specific sEV signatures characterized by enriched cell adhesion and immunomodulatory molecules. Furthermore, we revealed the significant contribution of cancer-associated fibroblasts in the sEV network within the TME. In vitro model-derived sEVs did not entirely inherit the extracellular matrix- and immunity regulation-related features of T-sEVs. Also, we demonstrated the greater immunostimulatory ability of T-sEVs on macrophages and CD8+ T cells compared to O-sEVs. Moreover, certain sEV biomarkers derived from noncancer cells in the circulation exhibited promising diagnostic potential. This study provides valuable insights into the functional characteristics of tumor tissue-derived sEVs, highlighting their potential as diagnostic markers and therapeutic agents for breast cancer.
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PURPOSE: Axillary lymph nodes (LN) are the primary and dominant metastatic sites in breast cancer. However, the interaction between tumor cells and immune cells within metastatic LNs (mLN) remains poorly understood. In our study, we explored the effect of CD24hiCD27+ regulatory B cells (Breg) within mLNs on orchestrating drug resistance of breast cancer cells. EXPERIMENTAL DESIGN: We collected mLN samples from patients with breast cancer who had received standard neoadjuvant therapy (NAT) and analyzed the spatial features of CD24hiCD27+ Bregs through multicolor immunofluorescence staining. The effect of CD24hiCD27+ Bregs on drug resistance of breast cancer cells was evaluated via in vitro experiments. A mouse model with mLNs was used to evaluate the strategies with blocking the interactions between Bregs and breast cancer for improving tumor regression within mLNs. RESULTS: In patients with breast cancer who had received NAT, there is a close spatial correlation between activated CD24hiCD27+ Bregs and residual tumor cells within mLNs. Mechanistically, CD24hiCD27+ Bregs greatly enhance the acquisition of multidrug resistance and stem-like features of breast cancer cells by secreting IL6 and TNFα. More importantly, breast cancer cells further promote the activation of CD24hiCD27+ Bregs via CD40L-dependent and PD-L1-dependent proximal signals, forming a positive feedback pattern. PD-L1 blockade significantly attenuates the drug resistance of breast cancer cells induced by CD24hiCD27+ Bregs, and addition of anti-PD-L1 antibody to chemotherapy improves tumor cell remission in mLNs. CONCLUSIONS: Our study reveals the pivotal role of CD24hiCD27+ Bregs in promoting drug resistance by interacting with breast cancer cells in mLNs, providing novel evidence for an improved strategy of chemoimmunotherapy combination for patients with breast cancer with mLNs.
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Linfocitos B Reguladores , Neoplasias de la Mama , Animales , Ratones , Humanos , Femenino , Neoplasias de la Mama/patología , Antígeno B7-H1 , Linfocitos B Reguladores/patología , Ganglios Linfáticos/patología , Resistencia a Múltiples MedicamentosRESUMEN
Background: Circulating tumor cells (CTCs) have been recognized as a sensitive biomarker for breast cancer (BC). This study aimed to comprehensively compare CTC with imaging modalities, including ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging (MRI) in screening for BC in Chinese women. Methods: Three hundred forty-three participants were enrolled in this study, including 102 treatment-naive BC patients, 177 with breast benign diseases (BBD) and 64 healthy female patients. All participants underwent CTC testing and at least one of the following examinations, ultrasonography, mammography, and MRI at the Second Affiliated Hospital of Zhejiang University between December 2017 and November 2020. CTCs were quantitatively assessed using cell counting (CTC detection rate/counts) and categorically examined using a cutoff value (CTC classification). The diagnostic power of CTC tests and imaging modalities, including accuracy and capability to predict clinicopathological characteristics of BC, were evaluated and compared. Results: CTC classification with a cutoff value of 2 showed a "good" diagnostic accuracy of 0.889 for early- to mid-stage BC comparable to breast imaging modalities using Breast Imaging-Reporting and Data System (BI-RADS). MRI demonstrated the highest sensitivity of 0.872 for BC, and CTC classification had the highest specificity of 0.938. A relatively low sensitivity was found for mammography in this cohort of patients. Successful detection of BC by CTC detection rate/counts, but not CTC classification, correlated with two important clinicopathological features, American Joint Committee on Cancer (AJCC) stage and tumor-node-metastasis (TNM) stage. The detection power of certain imaging modalities was also associated with AJCC stage (ultrasonography, p = 0.0438 and MRI, p = 0.0422) and lymph node metastasis (ultrasonography, 0.0157). There were clear correlations between CTC tests (counts or classification) and imaging BI-RADS scoring system in detecting positive BC cases (p < 0.05). Further correlation analysis suggested that CTC quantity, but not CTC classification, had the capability to predict clinicopathological traits of BC that were identified by ultrasonography. Conclusions: CTC tests have a diagnostic potency comparable to breast imaging modalities, and may be used as an alternative screening tool for BC.
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Accumulating evidence showed that cancer stem cells (CSCs) play significant roles in cancer initiation, resistance to therapy, recurrence and metastasis. Cancer stem cells possess the ability of self-renewal and can initiate tumor growth and avoid lethal factors through flexible metabolic reprogramming. Abnormal lipid metabolism has been reported to be involved in the cancer stemness and promote the development of cancer. Lipid metabolism includes lipid uptake, lipolysis, fatty acid oxidation, de novo lipogenesis, and lipid desaturation. Abnormal lipid metabolism leads to ferroptosis of CSCs. In this review, we comprehensively summarized the role of intra- and extracellular lipid signals in cancer stemness, and explored the feasibility of using lipid metabolism-related treatment strategies for future cancer.
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Tumor angiogenesis induces local hypoxia and recruits immunosuppressive cells, whereas hypoxia subsequently promotes tumor angiogenesis. Immunotherapy efficacy depends on the accumulation and activity of tumor-infiltrating immune cells (TIICs). Antangiogenic therapy could improve local perfusion, relieve tumor microenvironment (TME) hypoxia, and reverse the immunosuppressive state. Combining antiangiogenic therapy with immunotherapy might represent a promising option for the treatment of breast cancer. This article discusses the immunosuppressive characteristics of the breast cancer TME and outlines the interaction between the tumor vasculature and the immune system. Combining antiangiogenic therapy with immunotherapy could interrupt abnormal tumor vasculature-immunosuppression crosstalk, increase effector immune cell infiltration, improve immunotherapy effectiveness, and reduce the risk of immune-related adverse events. In addition, we summarize the preclinical research and ongoing clinical research related to the combination of antiangiogenic therapy with immunotherapy, discuss the underlying mechanisms, and provide a view for future developments. The combination of antiangiogenic therapy and immunotherapy could be a potential therapeutic strategy for treatment of breast cancer to promote tumor vasculature normalization and increase the efficiency of immunotherapy.
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Neoplasias de la Mama , Mastectomía , Mama/cirugía , Neoplasias de la Mama/cirugía , China , Femenino , Humanos , Instrumentos QuirúrgicosRESUMEN
:To establish and verify a risk prediction nomogram for ipsilateral axillary lymph node metastasis in breast cancer stage T1 ï¼mass ≤ 2 cmï¼. :The clinicopathological data of 907 patients with T1 breast cancer who underwent surgical treatment from January 2010 to June 2015 were collectedï¼including 573 cases from the Second Affiliated Hospital of Zhejiang University School of Medicine ï¼modeling groupï¼ and 334 cases from Zhejiang University Lishui Hospital ï¼verification groupï¼. The risk factors of ipsilateral axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression. The influencing factors were used to establish a nomogram for predicting ipsilateral axillary lymph nodes metastasis in T1 breast cancer. The model calibrationï¼predictive ability and clinical benefit in the modeling group and the verification group were analyzed by C indexï¼receiver operating characteristic curveï¼calibration curve and decision curve analysis ï¼DCAï¼ curveï¼respectively. :Univariate analysis showed that lymph node metastasis was related with primary tumor sizeï¼vascular tumor thrombusï¼Ki-67ï¼histopathological gradeï¼and molecular type ï¼<0.05 or <0.01ï¼. Multivariate logistic regression analysis showed that the primary tumor > vascular tumor thrombusï¼Ki-67 positiveï¼estrogen receptor ï¼ERï¼ positiveï¼and histopathological grade 2-3 were independent risk factors of axillary lymph node metastasis ï¼<0.05 or <0.01ï¼. Based on the independent risk factorsï¼a nomogram prediction model was established. The C indexes of the model group and the validation group were 0.739 ï¼95%:0.693-0.785ï¼ and 0.736 ï¼95%:0.678-0.793ï¼ï¼respectively. The calibration curve and DCA curve of the modeling group and the verification group indicated that the model was consistent and had good clinical benefit. :Primary tumor sizeï¼histopathological gradeï¼vascular tumor thrombusï¼Ki-67ï¼and ER status are predictors of ipsilateral axillary lymph node metastasis in T1 breast cancer. The established prediction nomogram can effectively predict the risk of ipsilateral axillary lymph node metastasis in T1 breast cancerï¼which can be used as a reference for individualized axillary management.
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Neoplasias de la Mama , Nomogramas , Axila , Femenino , Humanos , Ganglios Linfáticos , Metástasis Linfática , Estudios RetrospectivosRESUMEN
Breast cancer lung metastasis has a high mortality rate and lacks effective treatments, for the factors that determine breast cancer lung metastasis are not yet well understood. In this study, data from 1067 primary tumors in four public datasets revealed the distinct microenvironments and immune composition among patients with or without lung metastasis. We used multi-omics data of the TCGA cohort to emphasize the following characteristics that may lead to lung metastasis: more aggressive tumor malignant behaviors, severer genomic instability, higher immunogenicity but showed generalized inhibition of effector functions of immune cells. Furthermore, we found that mast cell fraction can be used as an index for individual lung metastasis status prediction and verified in the 20 human breast cancer samples. The lower mast cell infiltrations correlated with tumors that were more malignant and prone to have lung metastasis. This study is the first comprehensive analysis of the molecular and cellular characteristics and mutation profiles of breast cancer lung metastasis, which may be applicable for prognostic prediction and aid in choosing appropriate medical examinations and therapeutic regimens.
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Increasing evidence has revealed that the initiation and progression of breast cancer are greatly affected by the immune environment. Neutrophils are the most abundant leucocytes in circulation and act as the spearhead in inflammation, including in breast cancer. Circulating neutrophils are closely related to the prognosis of breast cancer patients, and tumor-infiltrating neutrophils have varied functions at different stages of breast cancer, such as antitumor or tumor-promoting neutrophils, which are termed N1 and N2 neutrophils, respectively. In this review, we will discuss the utility of circulating neutrophils for predicting prognosis and therapeutic efficacy and the underlying mechanisms of their chemotaxis, the dynamic regulation of their antitumor or protumor functions and their different spatial distributions in tumor microenvironment. Finally, we also discuss the possibility of targeting neutrophils as a therapeutic strategy in breast cancer.
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Neoplasias de la Mama/inmunología , Infiltración Neutrófila , Neutrófilos/inmunología , Escape del Tumor , Microambiente Tumoral , Animales , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Inmunoterapia , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Terapia Molecular Dirigida , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Fenotipo , Transducción de Señal , Escape del Tumor/efectos de los fármacosRESUMEN
Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of oxygen. In contrast, most cancer cells use less efficient glycolysis to produce ATP and essential biomolecules. Cancer cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth. A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells (CSCs). New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer cells. CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. The mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment. Targeting CSC metabolism may provide new and effective methods for the treatment of tumors. In this review, we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs, and discuss the clinical implications of targeting CSC metabolism.
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Skin cutaneous melanoma (SKCM) is characterized by both epigenetic DNA methylation (MET) abnormalities and genomic copy number variations (CNVs). The resulting transcriptome dysregulation promotes progression of many cancers. In this study, DNA copy numbers and MET, as well as mRNA expression, were examined in 466 SKCM samples from The Cancer Genome Atlas. Our results indicate that CNVs-correlated (CNVcor) genes and MET-correlated (METcor) genes are coregulated to a remarkable degree. In addition, integrative multi-omics analysis of both METcor and CNVcor genes revealed four SKCM subtypes with differing prognoses; these subtypes were validated with independent data. Immune cell scores were markedly elevated in the iC1 subtype, which had the best prognosis. Immune cell infiltration correlated with DNA MET or CNV level in SKCM. In the iC3 subtype, which was associated with the most aggressive SKCM cases, FAM135B gene mutation frequencies were increased, while CD8A, GBP5, KIAA0040, and SAMHD1 expression were downregulated, suggesting that these genes play important roles in cancer development and immune responses. Taken together, the results of our epigenetic and genomic transcriptome modulation analysis improve our understanding of SKCM pathobiology and may aid in the development of more effective therapies.
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Variaciones en el Número de Copia de ADN/genética , Metilación de ADN/genética , Melanoma , Neoplasias Cutáneas , Transcriptoma/genética , Epigenómica , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genómica , Humanos , Melanoma/clasificación , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Invasividad Neoplásica/genética , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
Tumour-infiltrating immune cells have been indicated to play an important role in prognosis prediction and therapy sensitivity for breast cancer. In recent years, estimating the abundance of immune cells based on tumour transcriptome data has provided a novel way to analyse the clinical significance of various immune cell subsets. This study integrated breast cancer tissue transcriptome datasets from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. A novel breast cancer immunotyping and a new prognostic model based on tumour-infiltrating immune cell subsets have been established, aiming to provide new clues regarding prognostic prediction and precision therapy for breast cancer. The key differentially expressed gene between different breast cancer immunotypes has also been identified. We performed unsupervised clustering analysis and construct a novel immunotyping which could classify breast cancer cases into immunotype A (B_cellhigh NKhigh CD8+_Thigh CD4+_memory_T_activatedhigh γδTlow Mast_cell_activatedlow Neutrophillow) and immunotype B (B_celllow NKlow CD8+_Tlow CD4+_memory_T_activatedlow γδThigh Mast_cell_activatedhigh Neutrophilhigh) in luminal B, HER2-enriched and basal-like subtypes. The 5-year (85.7% vs. 73.4%) and 10-year OS (75.60% vs. 61.73%) of immunotype A population were significantly higher than those of immunotype B. A novel tumour-infiltrating immune cell-based prognostic model had also been established and the result immunorisk score (IRS) could serve as a new prognostic factor for luminal B, HER2-enriched and basal-like breast cancer. The higher IRS was, the worse prognosis was. We further screened the differentially expressed genes between immunotype A and B and identified a novel breast cancer immune-related gene, prostaglandin D2 synthase (PTGDS) and higher PTGDS mRNA expression level was positively correlated with earlier TNM stage. Immune-related signaling pathways analysis and immune cell subsets correlation analysis revealed that PTGDS expression was related with abundance of B cells, CD4+ T cells and CD8+ T cells, which was finally validated by immunohistochemical and immunofluorescence staining. We established a novel immunotyping and a tumour-infiltrating immune cell-based prognostic prediction model in luminal B, HER2-enriched and basal-like breast cancer by analyzing the prognostic significance of multiple immune cell subsets. A novel breast cancer immune signature gene PTDGS was discovered, which might serve as a protective prognostic factor and play an important role in breast cancer development and lymphocyte-related immune response.
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The dependence of tumor growth on neovascularization has become an important aspect of cancer biology. Tumor angiogenesis is one of the key mechanisms of tumorigenesis, growth and metastasis. The key events involved in this process are endothelial cell proliferation, migration, and vascular formation. Recent studies have revealed the importance of tumor-associated endothelial cells (TECs) in the development and progression of colorectal cancer (CRC), including epithelial proliferation, stem cell maintenance, angiogenesis, and immune remodeling. Decades of research have identified that the molecular basis of tumor angiogenesis includes vascular endothelial growth factors (VEGFs) and their receptor family, which are the main targets of antiangiogenesis therapy. VEGFs and their receptors play key roles in the pathology of angiogenesis, and their overexpression indicates poor prognosis in CRC. This article reviews the characteristics of the tumor vasculature and the role of TECs in different stages of CRC and immune remodeling. We also discuss the biological effects of VEGFs and their receptor family as angiogenesis regulators and emphasize the clinical implications of TECs in clinical treatment.
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Atherosclerosis is the main pathological basis for the occurrence of most cardiovascular diseases, the leading global health threat, and a great burden for society. It has been well established that atherosclerosis is not only a metabolic disorder but also a chronic, sterile, and maladaptive inflammatory process encompassing both innate and adaptive immunity. Macrophages, the major immune cell population in atherosclerotic lesions, have been shown to play critical roles in all stages of atherosclerosis, including the initiation and progression of advanced atherosclerosis. Macrophages have emerged as a novel potential target for antiatherosclerosis therapy. In addition, the macrophage phenotype is greatly influenced by microenvironmental stimuli in the plaques and presents complex heterogeneity. This article reviews the functions of macrophages in different stages of atherosclerosis, as well as the phenotypes and functions of macrophage subsets. New treatment strategies based on macrophage-related inflammation are also discussed.
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Aterosclerosis/etiología , Aterosclerosis/metabolismo , Susceptibilidad a Enfermedades , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Biomarcadores , Citocinas/metabolismo , Descubrimiento de Drogas , Humanos , Mediadores de Inflamación/metabolismo , Activación de Macrófagos , Macrófagos/efectos de los fármacos , Macrófagos/patología , Terapia Molecular Dirigida , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/patología , Placa Aterosclerótica/etiología , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologíaRESUMEN
This study investigated the effect of fluorine (F) diffusion from a fluorinated siliconnitride passivation layer (SiNX:F-Pa) into amorphous-InGaZnO-based thin-film transistors (a-IGZO TFTs). The results of thermal desorption spectroscopy and secondary ion mass spectrometry revealed that F was introduced into the SiOX etch-stopper layer (SiOX-ES) during the deposition of a SiNX:F-Pa, and did not originate from desorption of Si-F bonds; and that long annealing times enhanced F diffusion from the SiOX-ES layer to the a-IGZO channel. Improvements to the performance and threshold-voltage (Vth) negative shift of IGZO TFTs were achieved when annealing time increased from 1 h to 3 h; and capacitance-voltage results indicated that F acted as a shallow donor near the source side in a-IGZO and induced the negative Vth shift. In addition, it was found that when IGZO TFTs with SiNX:F-Pa were annealed 4 h, a low-resistance region was formed at the backchannel of the TFT, leading to a drastic negative Vth shift.
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Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-ß. In this review, we focus on the TEX-induced immunosuppression and microenvironment change. Based on the truth that TEXs play crucial roles in suppressing the immune system, studies on modification of exosomes as immunotherapy strategies will also be discussed.
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Exosomas/inmunología , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Animales , Apoptosis , Proliferación Celular , Exosomas/química , Exosomas/genética , Humanos , Tolerancia Inmunológica , Inmunoterapia/métodos , Activación de Linfocitos , Ratones , Neoplasias/terapia , Transducción de Señal , Factor de Crecimiento Transformador beta , Microambiente Tumoral/genéticaRESUMEN
Epidemiological studies have reported an inconsistent relationship between maternal lipid levels and preterm birth (PTB). We performed this meta-analysis to evaluate the association between maternal dyslipidemia and PTB. Overall, three nested case-control studies and eight cohort studies were eligible. Effect estimates [odds ratio(OR)/relative risk] were pooled using a fixed-effects or a random-effects model. Subgroup and metaregression analyses were conducted to evaluate the sources of heterogeneity. Eleven studies involving 13,025 pregnant women were included. Compared with pregnant women with normal lipid levels, the women with elevated levels of lipids had an increased risk of PTB, and the pooled OR was 1.68 [95% confidence interval (CI): 1.25-2.26)]; meanwhile, women with lower levels of lipids also had a trend of an increased risk of PTB (OR=1.52, 95% CI=0.60-3.82). The pooled ORs for elevated levels of total cholesterol, triglycerides, low density lipoprotein-cholesterol, and lower levels of high density lipoprotein-cholesterol were 1.71 (95% CI: 1.05-2.79), 1.55 (95% CI: 1.13-2.12), 1.19 (95% CI: 0.95-1.48), and 1.33 (95% CI: 1.14-1.56), respectively. The present meta-analysis found that maternal dyslipidemia during pregnancy, either the elevated total cholesterol or triglycerides, was associated with an increased risk of PTB. These findings indicate that a normal level of maternal lipid during pregnancy may reduce the risk of PTB.
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Dislipidemias/complicaciones , Nacimiento Prematuro/etiología , Estudios de Casos y Controles , Colesterol/sangre , Estudios de Cohortes , Dislipidemias/sangre , Femenino , Humanos , Lípidos/sangre , Oportunidad Relativa , Embarazo , Complicaciones del Embarazo/sangre , Factores de Riesgo , Triglicéridos/sangreRESUMEN
ABSTACT Recombinant human Growth Hormone (rhGH) is an important protein for human growth and is in high demand in clinics. Hence, it is necessary to develop an efficient fermentation process to produce highly pure rhGH. In this study, rhGH was expressed in Escherichia coli under alkaline phosphatase (phoA) promoter. The cultivation conditions for high expression level and purity of rhGH were investigated. The best initial phosphate concentration for rhGH expression, out of the 4 levels of initial phosphate concentration tests performed, was 12.6 mmol/L. Subsequently, 2 fed-batch cultivations under low dissolved oxygen (DO) (0% - 10%) and high DO (20% - 30%) conditions were carried out. High purity rhGH (92%) was obtained from 20% - 30% DO-stat cultivation, although the biomass did not show any significant difference. In summary, this research provided an efficient fermentation process for high purity rhGH production from E. coli under phoA promoter, which can lower the production and purification costs for large-scale production of rhGH.
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Fosfatasa Alcalina/genética , Proteínas de Escherichia coli/genética , Hormona de Crecimiento Humana/biosíntesis , Regiones Promotoras Genéticas/genética , Proteínas Recombinantes/biosíntesis , Fosfatasa Alcalina/metabolismo , Escherichia coli , Fermentación , Hormona de Crecimiento Humana/genética , Humanos , Proteínas Recombinantes/genéticaRESUMEN
Across countries, the predominant diets are clearly different and highly related with human health. Therefore, it is necessary to evaluate dietary nutrients between them. This study aimed to evaluate dietary nutrients in China and compare those between Chinese and Mediterranean (Italian), Japanese and American diets. Dietary intakes of 2659 subjects in south-east China, Zhejiang province, from 2010 to 2012, were estimated by three consecutive 24-h dietary recalls. The contribution of carbohydrate to total energy in Chinese subjects was lower than that in Japanese and American subjects, but higher than that in Italian subjects. However, the energy contribution from fat in Chinese subjects was higher than that in Japanese and American subjects, and similar to that in Italian subjects. Moreover, the Chinese diet had lower daily intakes of fiber, calcium, phosphorus, potassium, selenium, vitamin A, vitamin B1, vitamin B2 and vitamin C, compared with the Japanese, American and Italian diets. Nevertheless, intakes of sodium, iron, copper and vitamin E were higher among Chinese people relative to the people of other three countries. The present study demonstrated that the structure of the Chinese diet has been shifting away from the traditional diet toward high-fat, low-carbohydrate and low-fiber diets, and nutrients intakes in Chinese people have been changing even worse than those in American people.