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Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis. Through WGCNA analysis, POSTN was identified as a key biomarker for CAFs associated with TNBC. Then, POSTN+CAFs was identified and characterized. Both POSTN and POSTN+CAFs showed significant positive correlations with stromal molecules HGF and MET at both the transcriptional and protein levels. Specifically co-localized with CAFs in the tumor stromal area, POSTN, produced by POSTN+CAFs, could modulate the HGF-MET axis, serving as a bypass activation pathway to regulate tumor cell proliferation in response to EGFR inhibitor and MET inhibitor. This study underscores the significance of POSTN and POSTN+CAFs as crucial targets for the diagnosis and treatment of TNBC.
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Fibroblastos Associados a Câncer , Moléculas de Adesão Celular , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-met , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Feminino , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/genética , Proliferação de Células , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , PrognósticoRESUMO
BACKGROUND: Total pelvic exenteration is the ultimate solution for rectovesicovaginal fistula caused by radiation therapy, yet total pelvic exenteration frequently causes intraoperative complications and postoperative complications. These complications are responsible for the dysfunction of lower extremities, impaired quality of life, and even the high long-term morbidity rate, thus multidisciplinary cooperation and early intervention for prevention of complications are necessary. Physical therapy was found to reduce the postoperative complications and promote rehabilitation, yet the effect on how physiotherapy prevents and treats complications after total pelvic exenteration and pelvic lymphadenectomy remains unclear. CASE PRESENTATION: A 50-year-old Chinese woman gradually developed perianal and pelvic floor pain and discomfort, right lower limb numbness, and involuntary vaginal discharge owing to recurrence and metastasis of cervical cancer more than half a year ago. Diagnosed as rectovesicovaginal fistula caused by radiation, she received total pelvic exenteration and subsequently developed severe lower limb edema, swelling pain, obturator nerve injury, and motor dysfunction. The patient was referred to a physiotherapist who performed rehabilitation evaluation and found edema in both lower extremities, right inguinal region pain (numeric pain rate scale 5/10), decreased temperature sensation and light touch in the medial thigh of the right lower limb, decreased right hip adductor muscle strength (manual muscle test 1/5) and right hip flexor muscle strength (manual muscle test 1/5), inability actively to adduct and flex the right hip with knee extension, low de Morton mobility Index score (0/100), and low Modified Barthel Index score (35/100). Routine physiotherapy was performed in 2 weeks, including therapeutic exercises, mechanical stimulation and electrical stimulation as well as manual therapy. The outcomes showed that physiotherapy significantly reduced lower limb pain and swelling, and improved hip range of motion, motor function, and activities of daily living, but still did not prevent thrombosis. CONCLUSION: Standardized physical therapy demonstrates the effect on postoperative complications after total pelvic exenteration and pelvic lymphadenectomy. This supports the necessity of multidisciplinary cooperation and early physiotherapy intervention. Further research is needed to determine the causes of thrombosis after standardized intervention, and more randomized controlled trials are needed to investigate the efficacy of physical therapy after total pelvic exenteration.
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Exenteração Pélvica , Trombose , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Atividades Cotidianas , Qualidade de Vida , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Extremidade Inferior , Modalidades de Fisioterapia , Dor Pélvica , Edema , Complicações Pós-Operatórias/terapiaRESUMO
Background: Triple-negative breast cancer (TNBC) is an aggressive cancer that affects about 13/100,000 women yearly. Patients with TNBC are often resistant to endocrine and molecular targeted therapy, making clinical treatment challenging. Researches indicate that tumor microenvironment (TME) is related to prognosis in many cancers. Therefore, we aim to identify TME immune-related biomarkers to enhance the prognosis and immunotherapy efficacy in patients with TNBC. Methods: The bulk mRNA transcriptome data and clinical information of the (GSE58812) and (GSE25055) datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the ESTIMATE algorithm was used to calculate the ImmuneScore, StromalScore, and ESTIMATEScore. Patients were divided into low and high groups according to the quartiles of ImmuneScore, StromalScore, and the median of ESTIMATEScore to filter differential expression genes (DEGs), respectively. The DEGs were then evaluated using univariate and multivariate Cox regression to identify TME-related genes and its association with survival rate for the construction of a TMErisk model with three biomarkers. Then Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) data were used to compare the gene expression in cancer and normal tissues. xCell analysis calculated the proportion of tumor-infiltrating immune cells in low and high expression of ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2). In addition, samples from 20 TNBC patients admitted to our institution were used for immunohistochemical (IHC) examination. Results: Three immune-related DEGs were identified, including prolyl 3-hydroxylase 2 (P3H2), sodium voltage-gated channel beta subunit 3 (SCN3B), and ATP2C2 and a TMErisk model was constructed and validated. However, only ATP2C2 was selected for further analysis. ATP2C2 mRNA level of TNBC patients was higher than that of normal breast tissue. Survival analysis showed that patients with high expression of ATP2C2 had a bad prognosis. xCell analysis demonstrated that the expression of ATP2C2 was associated with 16 kinds of tumor-infiltrating immune cells. Protein expression of ATP2C2 in TNBC tissues was higher compared to paired normal tissues in IHC. Conclusions: This study constructed and validated a TMErisk model that can effectively predict 3- and 5-year survival rate for TNBC patients. TNBC patients with lower expression of ATP2C2 had a good prognosis.
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Background: Tumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes. Methods: RNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools. Results: The risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P < 0.05). Low risk score was positively associated with plasma cells, memory B cells, CD8 T cells, regulatory T cells and γδT cells (P < 0.05). In low-risk group, programmed cell death 1 receptor (PD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3) and indoleamine 2,3-dioxygenase (IDO) were more robustly expressed (P < 0.05). The treatment responses of immune checkpoint blockade (ICB) therapy and chemotherapy were likewise superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly higher levels of CD79A, DKK1, and VEGFC than the adjacent normal group (P < 0.01). Conclusions: CD79A, DKK1 and VEGFC are important differential genes related to LUAD, risk score could reliably predict prognosis, composition of TIME and immunotherapy responses in LUAD patients. The excellent performance of the risk model shows its strong and broad application potential.
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Transition metal sulfides (TMSs) are considered as one of the promising electrode materials due to their fascinating redox reversibility and electronic conductivity. However, volume expansion during the charge/discharge process impedes their practical applications. The reasonable design of TMS electrode materials with unique morphology can improve the energy storage performance. Herein, we prepared the Ni3S2/Co9S8/NiS composite that is in situ grown on Ni foam (NF) via a one-step electrodeposition process. The optimized Ni3S2/Co9S8/NiS-7 shows a superhigh specific capacity of 2785.3 F g-1 at 1 A g-1 and remarkable rate capability. Furthermore, the as-assembled device displays a high energy density of 40.1 W h kg-1 at a power density of 799.3 W kg-1 and a satisfactory stability of 96.6% retention after 5000 cycles. This work provides a facile way to fabricate new TMS electrode materials for high-performance supercapacitors.
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It is important to develop highly efficient and durable Earth-abundant oxygen evolution reaction (OER) electrocatalysts by an energy- and time-saving strategy. Herein, a facile strategy was used to synthesize S-doped nickel-iron oxyhydroxide (S-Ni/FeOOH) nanoparticles on nickel-iron foam (NFF) (S-Ni/FeOOH@NFF), which exhibits a striking enhancement of OER performance compared to Ni/FeOOH@NFF. The free-standing S-Ni/FeOOH@NFF electrode possesses a low overpotential of 229 mV at a current density of 10 mA cm-2, which is 180 mV lower than that of Ni/FeOOH@NFF. In addition, the electrode was also remarkably stable. The current density still remains at 95% after 150 h at a high current density of 100 mA cm-2.
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Nanopartículas , Níquel , Eletrodos , Ferro , OxigênioRESUMO
Constructing a heterostructure is an efficient strategy to enhance the catalytic activity toward the oxygen evolution reaction (OER). Herein, Ce-modified Ni(OH)2 nanoparticles are anchored on Ni-MOF nanosheets by the electrodeposition strategy, forming a self-supporting electrode of Ce-m-Ni(OH)2@Ni-MOF. The Raman spectrum proves that both Ce(OH)3 and Ce doping exist in Ce-modified Ni(OH)2 nanoparticles. The heterostructure possesses an open nanosheet structure, with a good interaction between Ni-MOF and Ce-m-Ni(OH)2, which enables efficient mass/charge transfer and the synergetic effect between Ni and Ce, leading to a high-performance electrocatalyst. Specifically, Ce-m-Ni(OH)2@Ni-MOF achieves current densities of 50 and 100 mA cm-2 at low overpotentials of 219 and 272 mV, respectively, and retains high activity for at least 30 h.
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2D bimetal metal organic frameworks (MOFs) are recognized as one of the most promising electrocatalysts for the oxygen evolution reaction (OER). Herein, a facile approach was proposed to construct NiFe-MOF nanosheets on Fe foam (FF). As a self-supporting electrode, the NiFe-MOF/FF electrode shows impressive electrocatalytic OER performance. Specifically, it exhibits an ultra-low overpotential of 216 mV to reach a current density of 50 mA cm-2, and outstanding stability (beyond 50 h at 200 mA cm-2). The excellent performances of NiFe-MOF/FF arise from the highly exposed active centers, the excellent conductivity, and the synergy effect between Ni and Fe. This research provides a promising strategy for the synthesis of multi-metal MOFs as high-efficiency electrocatalysts.
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Rational design and controllable synthesis of metal-organic frameworks nanosheets is critical for electrochemical catalysis. Herein, a carnation-like ZIF-9 nanostructure made of nanosheets is grown on nickel foam (ZIF-9/NF) by a simple one-step solvothermal method, the morphology evolution and the electrocatalytic oxygen evolution properties have been investigated by controlling the solvothermal time. The binder-free ZIF-9-d/NF (60 h, solvothermal time is 60 h) electrode delivers efficient electrocatalytic oxygen evolution reaction activity with low overpotentials of 312 and 337 mV at 50 and 100 mA cm-2, respectively. Furthermore, ZIF-9-d/NF (60 h) exhibits excellent stability without obvious attenuation for at least 30 h at 200 mA cm-2. The excellent performances can be attributed to the combination of the highly exposed active sites in the ZIF-9-d nanosheets, as well as the effective electron conduction and mass transfer. This work provides much possibilities for ZIF-9 nanosheets as binder-free electrode for electrocatalyst.
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The function of centromere protein U (CENPU) gene in breast cancer has not been well understood. Therefore, we explored the expression profiles of CENPU gene in breast carcinoma to better understand the functions of this gene, as well as the relationship between CENPU expression and the prognosis of breast carcinoma patients. Our results indicate that CENPU was expressed at significantly higher levels in cancerous tissues than in normal tissues. Furthermore, CENPU expression correlated significantly with many clinicopathological characteristics of breast cancer. In addition, we discovered that high levels of CENPU expression predicted poor prognosis in patients with breast cancer. Functional investigation revealed that 180 genes exhibited co-expression with CENPU. Functional annotation indicated that 17 of these genes were involved in the PLK1 signaling pathway, with most of them (16/17) being expressed at significantly higher levels in malignant tissues compared with normal controls and correlating with a poor prognosis. Subsequently, we found that four miRNAs, namely hsa-miR-543, hsa-miR-495-3p, hsa-miR-485-3p, and hsa-miR-337-3p, could be regarded as potential CENPU expression regulators. Then, five lncRNAs were predicted to potentially bind to the four miRNAs. Combination of the results from expression, survival, correlation analysis and functional experiments analysis demonstrated the link between lncRNA GATA3-AS1/miR-495-3p/CENPU axis and prognosis of breast cancer. In conclusion, CENPU could be involved in cell cycle progression through PLK1 signaling pathway.
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Neoplasias da Mama/genética , Proteínas de Ciclo Celular/metabolismo , Histonas/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , Mutação/genética , Prognóstico , RNA Longo não Codificante/genética , Quinase 1 Polo-LikeRESUMO
BACKGROUND: Sperm-associated antigen 1 (SPAG1) has been identified as a marker of pancreatic cancer progression and promoter of cell motility; however, its role in breast cancer is not completely understood. METHODS: SPAG1 expression in breast cancer tissues and normal tissues was obtained from online databases. Knockdown function assays were designed and conducted to verify the functional role of SPAG1 in breast cancer cell lines. Cell counting and MTT assays were used to assess cell proliferation. Cell flow cytometry assay was used for cell cycle phase arrest, and fluorescence microscopy was used for colony formation assessment. RESULTS: Both the mRNA and protein levels of SPAG1 were significantly higher in the breast cancer tissues than in the normal tissues. In addition, SPAG1 is significantly related to many clinicopathological features of breast cancer, such as age (>51 years), estrogen receptor (ER) (+), progesterone receptor (PR) (+), and nodal status (+), non-triple negative breast cancer (TNBC), not basal-like and not basal-like and not TNBC. Survival analysis indicates that breast cancer patients with low expression of SPAG1 had a significantly better prognosis with relapse-free survival (RFS). Functional experiment analysis revealed that knockdown of SPAG1 suppressed cell proliferation and colony-forming ability. CONCLUSION: Our results suggested a possible role of SPAG1 in breast cancer pathogenesis.
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Robust and economical catalysts are imperative to realize the versatile applications of hydrogen. Herein, a 1T-MoS2/N-doped NiSe2 composite was rationally synthesized via a solvothermal method, in which the MoS2 nanosheets have a stable 1T phase structure, and the NiSe2 nanoparticles serve as a cocatalytic support for MoS2. The nonnegligible electronic couplings between NiSe2 and MoS2 could facilitate the optimization of their electronic structure and then improve the hydrogen adsorption. What is more, the nitrogen dopants in the NiSe2 nanoparticles could intensify the intercalation of ammonium ions in the 1T-MoS2 nanosheets, and further enlarge their interlayer spacing, thus the electrolyte could infiltrate into the catalyst more easily and sufficiently. This work provides a new route for rationally designing highly active and low cost hydrogen evolution reaction (HER) catalysts, and enriches the study of transition metal chalcogenides toward HER.
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Vulnerable atherosclerotic (AS) plaque is the major cause of cardiovascular death. However, clinical methods cannot directly identify the vulnerable AS plaque at molecule level. Herein, osteopontin antibody (OPN Ab) and NIR fluorescence molecules of ICG co-assembled Ti3 C2 nanosheets are reported as an advanced nanoprobe (OPN Ab/Ti3 C2 /ICG) with enhanced photoacoustic (PA) performance for direct and non-invasive in vivo visual imaging of vulnerable AS plaque. The designed OPN Ab/Ti3 C2 /ICG nanoprobes successfully realize obvious NIR fluorescence imaging toward foam cells as well as the vulnerable AS plaque slices. After intravenous injection of OPN Ab/Ti3 C2 /ICG nanoprobes into AS model mice, in vivo imaging results show a significantly enhanced PA signal in the aortic arch accumulated with vulnerable plaque, well indicating the remarkable feasibility of OPN Ab/Ti3 C2 /ICG nanoprobes to distinguish the vulnerable AS plaque. The proposed OPN Ab/Ti3 C2 /ICG nanoprobes not only overcome the clinical difficulty to differentiate vulnerable plaque, but also achieve the non-invasively specific in vivo imaging of vulnerable AS plaque at molecule level, greatly promoting the innovation of cardiovascular diagnosis technology.
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Nanotecnologia/métodos , Técnicas Fotoacústicas/métodos , Placa Aterosclerótica/diagnóstico por imagem , Animais , Camundongos , Nanopartículas/química , Osteopontina/químicaRESUMO
The development of Li-S batteries is largely impeded by the growth of Li dendrites and polysulfide shuttling. To solve these two problems simultaneously, herein the study reports a "single atom array mimic" on ultrathin metal organic framework (MOF) nanosheet-based bifunctional separator for achieving the highly safe and long life Li-S batteries. In the designed separator, the periodically arranged cobalt atoms coordinated with oxygen atoms (CoO4 moieties) exposed on the surface of ultrathin MOF nanosheets, "single atom array mimic", can greatly homogenize Li ion flux through the strong Li ion adsorption with O atoms at the interface between anode and separator, leading to stable Li striping/plating. Meantime, at the cathode side, the Co single atom array mimic serves as "traps" to suppress polysulfide shuttling by Lewis acid-base interaction. As a result, the Li-S coin cells with the bifunctional separator exhibit a long cycle life with an ultralow capacity decay of 0.07% per cycle over 600 cycles. Even with a high sulfur loading of 7.8 mg cm-2 , an areal capacity of 5.0 mAh cm-2 can be remained after 200 cycles. Moreover, the assembled Li-S pouch cell displays stable cycling performance under various bending angles, demonstrating the potential for practical applications.
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Centromere protein U (CENPU) is a novel transcriptional repressor that is associated with different types of cancer. However, its function in breast cancer is poorly understood. In the present study, it was identified that CENPU was highly expressed in breast cancer tissues compared with expression in normal breast tissues (P=0.001). Furthermore, the CENPU mRNA level in tumors was often elevated, compared with the matched adjacent normal breast cancer tissue specimens in the dataset from The Cancer Genome Atlas database (n=106; P<0.001). To understand the function of CENPU in human breast carcinogenesis, its effects on the proliferation, apoptosis and cell cycle progression of MDA-MB-231 cells were examined using the lentiviral-mediated CENPU knockdown approach. The RNA and protein expression levels in the transfected cells were monitored using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The mRNA and protein expression levels of the CENPU gene were significantly lower in the CENPU-shRNA transfected cells than in the control (P<0.01), indicating successful gene expression knockdown. Post-transfection, cell counting and MTT analysis revealed that the proliferation activity was significantly suppressed in CENPU knockdown cells relative to the control (P<0.01). Additionally, fluorescence activated cell sorting analysis revealed that the (G2+S) phase fraction was significantly declined in CENPU knockdown cells relative to the control; while the G1 phase fraction was significantly increased (P<0.01) and the percentage of the apoptotic cells was significantly increased (P<0.01). In conclusion, downregulation of CENPU gene expression may inhibit cell proliferation and cell cycle progression, and increase the apoptosis of the breast cancer cells. These results suggested a possible function of this protein in breast cancer pathogenesis and prognosis.
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OBJECTIVE: Lung cancer, which is the leading cause of cancer death worldwide, is influenced by a wide variety of environmental and genetic risk factors. The silent information regulator 1 (SIRT1) gene is located on the long arm of chromosome 10 (10q21.3) and has been shown to play crucial roles in lung cancer development in previous studies. In this study, we determined whether variation in the SIRT1 gene is associated with lung cancer in Chinese population. METHODS: The case-control study comprised 246 controls and 257 non-small cell lung cancer patients, comprising 79 squamous cell carcinoma patients and 124 adenocarcinoma patients. All subjects were from Zhejiang, China. Four single-nucleotide polymorphisms of SIRT1 gene were analyzed: rs12778366 (C/T, lies in the 5' upstream), rs3758391 (C/T, lies in the 5' upstream), rs2273773 (C/T, lies in the coding) and rs4746720 (C/T, lies in the 3' untranslated region). RESULTS: No significant difference of allele and genotype frequencies was observed between the different groups. Haplotype association analysis carried out on the four single-nucleotide polymorphisms within the case-control cohort also did not reveal a significant association with lung cancer (P>0.05). CONCLUSION: The results suggest the tested SIRT1 gene polymorphisms may not contribute to lung cancer. Further studies are warranted to demonstrate the functional roles of the SIRT1 polymorphism in lung cancer.
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BACKGROUND AND AIMS: Matrix metalloproteinase-9 (MMP-9) -1562 C/T gene polymorphism has been identified as a susceptible gene for multiple autoimmune diseases (ADs), but studies are inconsistent. The aim of this study was to assess the overall association between MMP-9 gene polymorphism and multiple ADs using a meta-analysis. METHODS: Databases of Pubmed, Embase and Web of Science updated to March 1, 2016 were retrieved. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) as effect size were calculated by fixed-effect or random-effect model on the basis of heterogeneity. RESULTS: A total of 12 relevant studies containing 2,034 cases and 1,861 controls were included in this meta-analysis. A significant association between MMP-9 -1562 T allele and AD susceptibility was found in the overall population (OR = 1.269, 95% CI = 1.114-1.444, p <0.001) and the Caucasian populations (OR = 1.222, 95% CI = 1.051-1.422, p = 0.009), but not in the Asian populations (OR = 1.337, 95% CI = 0.989-0.808, p = 0.059). Stratified by disease type, we detected a significant association in other ADs (OR = 1.501, 95% CI = 1.212-1.859, p <0.001), but not in patients with multiple sclerosis (OR = 1.150, 95% CI = 0.977-1.354, p = 0.092). No publication bias was detected in the current meta-analysis. CONCLUSIONS: Data from the present study suggest that the MMP-9 -1562 C/T polymorphism may be associated with multiple AD susceptibility, especially in the Caucasian populations and other ADs. Further epidemiological studies with a larger sample size are needed to confirm these findings.
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Doenças Autoimunes/genética , Metaloproteinase 9 da Matriz/genética , Alelos , Povo Asiático , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Viés de Publicação , População BrancaRESUMO
Three µ4-O bridged Dy4 squares, {[Dy4(µ4-O)(HL1)4(H2O)4]2(NO3)3(OH)}·2H2O·2CH3OH (1), [Dy4(µ4-O)(HL2)4(SCN)2]·2H2O·4CH3OH (2) and [Dy4(µ4-O)(H2L3)2(SCN)2]·6H2O (3) were assembled by using a Schiff base ligand and its dimerized and reduced congener, respectively. These complexes share a similar µ4-O bridged Dy4 core, while, both the coordination geometry and metal-ligand interactions are slightly changed upon the modulation of the ligands, resulting in distinct single-molecular magnetic (SMM) and single-molecular toroic (SMT) properties. In complex 1, the Schiff base ligands are in an antiparallel fashion and all DyIII ions are in a similar coordination geometry, realizing the toroidal arrangement of magnetic moments. For complex 2, the reduced ligand H3L2 in a parallel fashion results in double relaxation processes and a 9-fold increase of the Ueff. Interestingly, with the use of the dimerized ligand H6L3, we obtained complex 3, which is similar to complex 2, while due to the slight changes of the coordination environment both the single molecular magnetic property and toroidal magnetic moments almost disappeared.
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The roles of Silent mating type information regulation 2 homolog 1 (SIRT1) and High mobility group A1 (HMGA1) in human diseases have been extensively studied separately; however, to the best of our knowledge, the current study is the first to report on their interrelationship in lung cancer. The association of SIRT1 and HMGA1 in non-small cell lung cancer (NSCLC) was investigated by evaluating their expression and prognostic significance in 260 patients with NSCLC using immunohistochemistry. SIRT1 and HMGA1 expression were found to be significantly correlated with each other (P<0.001), and both were significantly associated with clinicopathological parameters, including histological type and degree of differentiation. In squamous cell carcinoma (SCC), SIRT1+ specimens were significantly associated with shorter overall survival (OS) time (P=0.019). However, in patients with adenocarcinoma (AD), no association was identified between SIRT1 and OS. In addition, HMGA1+ specimens were significantly associated with poor differentiation (P=0.028), and were more frequent in SCC than AD (P=0.015). However, HMGA1 was not associated with OS on univariate Cox regression analysis or Kaplan-Meier analysis (both P>0.05). SIRT1/HMGA1 coexpression was significantly associated with male gender (P=0.016), and moderately and poorly differentiated histological grade (P=0.025). The findings indicate that SIRT1 and HMGA1 may have significant effects during tumor progression in NSCLC, particularly in patients with SCC, and are potentially useful as prognostic indicators for patients with NSCLC.
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The synthesis, structural characterization, and magnetic properties of four related heterometallic complexes with formulas [Dy(III)2Co(II)(C7H5O2)8]·6H2O (1), [Dy(III)2Ni(II)(C7H5O2)8]·(C7H6O2)2 (2), Tb(III)2Co(II)(C7H5O2)8 (3), and Dy(III)2Cd(II)(C7H5O2)8 (4) were reported. Each of complexes has a perfectly linear arrangement of the metal ions with two terminal Ln(III) (Ln(III) = Dy(III), Tb(III)) ions and one central M(II) (M(II) = Co(II), Ni(II), Cd(II)) ion. It was found that 1-3 displayed obvious magnetic interactions between the spin carriers according to the direct current (dc) susceptibility measurements. Alternating current (ac) magnetic susceptibility measurements indicate that complexes 1-4 all exhibit single-molecule magnet (SMM) behavior, while the replacement of the diamagnetic Cd(II) by paramagnetic ions leads to a significant slowing of the relaxation thanks to the magnetic interactions between 3d and 4f ions, resulting in higher relaxation barrier for complexes 1 and 2. Moreover, both Dy2Co and Dy2Ni compounds exhibit dual relaxation pathways that may originate from the single ion behavior of individual Dy(III) ions and the coupling between Dy(III) and Co(II)/Ni(II) ions, respectively, which can be taken as the feature of 3d-4f SMMs. The Ueff for 1 of 127 K is a relatively high value among the reported 3d-4f SMMs. The results demonstrate that the magnetic coupling between 3d and 4f ions is crucial to optimize SMM parameters. The synthetic approach illustrated in this work represents an efficient route to design nd-4f based SMMs via incorporating suitable paramagnetic 3d and even 4d and 5d ions into the d-f system.