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BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.
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Epilepsias Parciais , Proteínas de Homeodomínio , Espasmos Infantis , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Epilepsias Parciais/genética , Epilepsias Parciais/tratamento farmacológico , Sequenciamento do Exoma , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Mutação , Espasmos Infantis/genética , DrosophilaRESUMO
Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.
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Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Hospitalização , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/tratamento farmacológico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Transplante Autólogo , Idoso , Taxa de Sobrevida , Adulto Jovem , Quimioterapia de Manutenção , Autoenxertos , Indução de Remissão , AdolescenteRESUMO
OBJECTIVES: Microwave ablation (MWA) has been widely used for unifocal papillary thyroid carcinoma (U-PTC) and has recently been preliminarily used in multifocal papillary thyroid carcinoma (M-PTC). However, the efficacy and safety of MWA for M-PTC have not been investigated in large samples. The aim of the present study was to evaluate the efficacy and safety of MWA for M-PTC and compare them with MWA for U-PTC. MATERIALS AND METHODS: This retrospective multicentre study enrolled 504 patients (376 females) who underwent MWA for U-PTC (340 cases) or M-PTC (164 cases) from Jan 2015 to Dec 2020. The median age of the patients was 43 years (age range, 20-80 years). Propensity score matching (PSM) was used to balance the baseline characteristics between M-PTC group and U-PTC group. The tumour progression, tumour disappearance, and complication rates were compared between the two groups. RESULTS: The complete ablation was achieved in all enrolled cases in one session. According to the statistical results, no significant differences were shown in tumour progression-free survival (p = 0.29) or cumulative tumour progression rate (6.7% vs. 4.3%, p = 0.33) between the M-PTC and U-PTC groups during the follow-up time. However, the tumour disappearance rate in the M-PTC group was lower in the U-PTC group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the M-PTC group (p < 0.001). The complication rate showed no significant difference (3.0% vs. 4.9%, p = 0.571). CONCLUSIONS: MWA is an effective and safe treatment for selected patients with M-PTC, and the prognosis is similar to that of U-PTC. CLINICAL RELEVANCE STATEMENT: The present study provided evidence that compared with unifocal papillary thyroid cancer, microwave ablation could also treat multifocal T1N0M0 papillary thyroid cancer safely with similar clinical outcome, which could promote the application of minimally invasive treatment for papillary thyroid cancer. KEY RESULTS: ⢠Microwave ablation for multifocal and unifocal T1N0M0 papillary thyroid carcinoma had similar tumour progression rates after propensity score matching (6.7% vs. 4.3%, p = 0.33). ⢠The tumour disappearance rate in the multifocal group was lower than that in the unifocal group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the multifocal group (p < 0.001). ⢠Tumour size, number, and location were not risk factors for tumour progression in the multifocal papillary thyroid cancer group.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Resultado do Tratamento , Micro-Ondas/uso terapêutico , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologiaRESUMO
OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.
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Ablação por Radiofrequência , Neoplasias da Glândula Tireoide , Humanos , Micro-Ondas/uso terapêutico , Estudos Prospectivos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Ablação por Radiofrequência/métodos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.
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Ablação por Cateter , Nódulo da Glândula Tireoide , Ablação por Cateter/métodos , Seguimentos , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
An easily prepared fluoro-functionalized ionic covalent organic framework (F-iCOF) has been implemented into MALDI-TOF MS, enabling the highly selective enrichment and sensitive determination of perfluorinated sulfonate (PFS) contaminants in a rapid and convenient manner. The good thermal stability and excellent optical absorption properties of F-iCOF makes it a brilliant matrix with no background noise. Moreover, benefitting from the large surface area, appropriate pore size, good water dispersibility, and abundant fluorine atom and cationic characteristic of F-iCOF, it exhibited superior adsorption capacity and enrichment selectivity towards PFSs. Good signal responses for PFSs were obtained in the presence of various interfering compounds such as BSA, HA, or even more than 100-fold excess of glutamic acid and similar in structure sodium alkyl sulfonates, highlighting the specific selectivity of F-iCOF. Calibration curves for potassium perflurobutane sulfonate (PFBSK) in tap water and whole blood were established with good linear correlation in the range 1-500 pg mL-1. The limits of detection and quantification for PFBSK were as low as 0.04 pg mL-1 and 0.05 pg mL-1, respectively, which are comparable or better than the existing methods for the determination of PFSs.
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Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adsorção , Íons , Alcanossulfonatos , Água/químicaRESUMO
Coral-like Ag-Mo2C/C-I and blocky Ag-Mo2C/C-II composites were obtained from one-step in situ calcination of [Ag(HL)3(Mo8O26)]n·nH2O [L: N-(pyridin-3-ylmethyl) pyridine-2-amine] under N2/H2 and N2 atmospheres, respectively. The coral-like morphology of Ag-Mo2C/C-I is composed of interwoven nanorods embedded with small particles, and the nano-aggregate of Ag-Mo2C/C-II is formed by cross-linkage of irregular nanoparticles. The above composites are decorated on glassy carbon electrode (GCE) drop by drop to generate two enzyme-free electrochemical sensors (Ag-Mo2C/C/GCE) for amperometric detection of H2O2. In particular, the coral-like Ag-Mo2C/C-I/GCE sensor possesses rapid response (1.2 s), high sensitivity (466.2 µA·mM-1·cm-2), and low detection limit (25 nM) towards trace H2O2 and has wide linear range (0.08 µM~4.67 mM) and good stability. All these sensing performances are superior to Ag-Mo2C/C-II/GCE, indicating that the calcining atmosphere has an important influence on microstructure and electrochemical properties. The excellent electrochemical H2O2 sensing performance of Ag-Mo2C/C-I/GCE sensor is mainly attributed to the synergism of unique microstructure, platinum-like electron structure of Mo2C, strong interaction between Mo and Ag, as well as the increased active sites and conductivity caused by co-doped Ag and carbon. Furthermore, this sensor has been successfully applied to the detection of H2O2 in human serum sample, contact lens solution, and commercial disinfector, demonstrating the potential in related fields of environment and biology. Graphical abstract.
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BACKGROUND: This study is to describe the distribution of natural true anastomoses associated with the distally based perforator-plus sural neurocutaneous flap (sural flap), summarize our experience in the flap with high pivot point, and compare the outcomes between the flaps with high and low pivot points. METHODS: Five amputated lower limbs were perfused, and the integuments were radiographed. We retrospectively analyzed 378 flaps, which were divided into two groups: pivot points located ≤8.0 cm (low pivot point group) and >8.0 cm (high pivot point group) proximal to the tip of the lateral malleolus. Partial necrosis rates were compared between two groups. RESULTS: The arterial chain surrounding the sural nerve was linked by true anastomoses from the intermalleolar line to popliteal crease. True anastomoses existed among peroneal perforators and between these perforators and the arterial chain. There were 93 flaps with high pivot point and 285 flaps with low pivot point. Partial necrosis rates were 16 and 9.1% in the high and low pivot point group (p = 0.059), respectively. CONCLUSION: True anastomosis connections among peroneal perforators and the whole arterial chain around sural nerve enable the sural flap to survive with a greater length. The sural flap with high pivot point is a good option for reconstructing soft-tissue defects in the middle and distal leg, ankle, and foot, particularly when the lowest peroneal perforator presents damage, greater distance to the defects, discontinuity with the donor site, or anatomical variation.
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Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Tornozelo , Pé , Humanos , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Nervo SuralRESUMO
Immune processes in liver transplantation remain poorly understood. Acute allograft rejection in liver transplantation is a kind of T cell-mediated inflammatory disease accompanied by inflammatory cell infiltration. However, the effect of acute allograft rejection on the immunological characteristics of TCRs in peripheral blood mononuclear cell is unknown. In this study, we characterized the pattern of the human T cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) complementarity-determining region 3 (CDR3) repertoires via high-throughput sequencing in 11 acute allograft rejection (AG) cases, 23 patients with stable allograft liver function (ST) who had liver transplantation performed and 20 healthy controls (HC). The diversity of TRB-CDR3 was significantly reduced in the AG group compared with the ST group and healthy controls (HC). The CDR3 and N-addition length distribution were not significantly different between the AG and ST groups. However, N-addition length distribution was significantly changed compared to HC. It seemed that AG used more short N-additions and healthy people used more long N-additions in TRB-CDR3 repertoire. Our findings suggested that the TRB-CDR3 region of AG had distinctive V gene use compared with that of HC. The characteristics of ST seemed to be in between those of AG and HC although the difference is not significant. Cluster analysis showed that the TRB repertoire could not effectively distinguish AG from ST. This research might give to a better understanding of the immune process of liver transplantation.
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Regiões Determinantes de Complementaridade/imunologia , Rejeição de Enxerto/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Transplante de Fígado , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adulto , Regiões Determinantes de Complementaridade/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genéticaRESUMO
BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.
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Infecções por Citomegalovirus/complicações , Neoplasias Gastrointestinais/etiologia , Idoso , Anticorpos Antivirais/sangue , Estudos Transversais , Citomegalovirus/genética , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , DNA Viral/análise , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Long noncoding RNA (lncRNA) exerts a potential regulatory role in tumorigenesis. LncRNA TUG1 expression remains high in oral squamous cell carcinoma (OSCC) tissues. However, its biological mechanism in OSCC remains unknown. In this study, TUG1 expression in OSCC cells was detected by quantitative real-time polymerase chain reaction. Proliferative and migratory potentials of OSCC cells were determined by Cell Counting Kit 8, 5-Ethynyl-2'- deoxyuridine (EdU), and Transwell assay, respectively. We identified the potential target of TUG1 through bioinformatics and dual-luciferase reporter gene assay. Furthermore, their interaction and functions in regulating the development of OSCC were clarified by western blot and RNA immunoprecipitation assay. Our results demonstrated a high expression of TUG1 in OSCC cells. Overexpression of TUG1 markedly accelerated proliferative and migratory potentials of OSCC cells. Besides, TUG1 could positively regulate the expression of distal-less homeobox 1 (DLX1) by competing with miR-524-5p. These results indicated that TUG1 participated in the development of OSCC as a competing endogenous RNA to competitively bind to miR-524-5p and thus mediate DLX1 expression.
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Carcinoma de Células Escamosas/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Apoptose/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Bucais/patologiaRESUMO
Circular RNAs (circRNAs) can participate in multiple cancers, including breast cancer. Increasing circRNAs are recognized in various cancers because of the high-throughput sequencing. However, the potential physiological effect of hsa_circ_0136666 in breast cancer progression is unknown. In our study, the biological role of hsa_circ_0136666 in breast cancer development was studied. It was displayed that hsa_circ_0136666 was greatly increased in breast cancer. In addition, overexpression of hsa_circ_0136666 was able to promote Michigan Cancer Foundation-7 (MCF7) and BT474 cell proliferation and triggered cell cycle in G2/M phase. microRNA plays critical role in tumor development and they can act as direct targets of circRNAs. miR-1299 has been implicated as a famous tumor suppressor in many cancers. Here, miR-1299 was predicted as the target of hsa_circ_0136666. Meanwhile, its Upregulation repressed breast cancer proliferation, migration and invasion capacity, which could be reversed by the increase of hsa_circ_0136666. Furthermore, Cyclin-dependent kinase 6 (CDK6) was speculated as the downstream target of miR-1299. In MCF7 and BT474 cells, CDK6 was greatly overexpressed and it was shown that CDK6 contributed a lot to breast cancer progression. Subsequently, it was implied that hsa_circ_0136666 could modulate CDK6 levels positively in vitro. In conclusion, it was revealed that Upregulation of hsa_circ_0136666 promoted breast cancer progression by sponging miR-1299 and targeting CDK6.
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Neoplasias da Mama/genética , Quinase 6 Dependente de Ciclina/genética , MicroRNAs/genética , RNA Circular/genética , Regulação para Cima , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7RESUMO
The microRNA (miRNA) miR-125b is abnormally expressed in many different types of tumors, including osteosarcoma (OS). How aberrantly expressed miR-125b participates in regulating the initiation and progression of OS is still poorly understood. In the current study, we found that in OS, miR-125b can suppress the expression of MAP kinase kinase 7 (MKK7), which can dephosphorylate and inactivate signal transducer and activator of transcription 3 (STAT3). We also identified an elevated expression level of MKK7 in OS and an association between MKK7 expression and poor prognosis. Further, miR-125b inhibited OS cell proliferation and invasion by targeting and downregulating MKK7 in vitro and suppressed tumor formation in vivo. Moreover, using Western blot analysis, we preliminarily proved that the activation (phosphorylation) of STAT3 was regulated by MKK7 at the epigenetic level. MKK7 was overexpressed in OS and associated with poor clinical results. The miR-125b-MAPK-STAT3 axis may be one of the mechanisms of OS oncogenesis and a potential target for the treatment of OS.
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Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.
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Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mitofagia/efeitos dos fármacos , Mitofagia/genética , Terapia de Alvo Molecular , Saponinas/farmacologia , Animais , Linhagem Celular , Dipsacaceae/química , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fitoterapia , Ratos , Saponinas/uso terapêuticoRESUMO
Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.
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Aterosclerose/etiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Adulto , Anticorpos Antivirais/sangue , Aterosclerose/virologia , Citomegalovirus/genética , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/etnologia , DNA Viral/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Fatores de Risco , Proteínas da Matriz Viral/isolamento & purificaçãoRESUMO
Eu2+-doped La3Si8N11O4 phosphors were synthesized by the high temperature solid-state method, and their photoluminescence properties were investigated in this work. La3Si8N11O4:Eu2+ exhibits a strong broad absorption band centered at 320 nm, spanning the spectral range of 300-600 nm due to 4f7 â 4f65d1 electronic transitions of Eu2+. The emission spectra show a broad and asymmetric band peaking at 481-513 nm depending on the Eu2+ concentration, and the emission color can be tuned in a broad range owing to the energy transfer between Eu2+ ions occupying two independent crystallographic sites. Compared to the Ce3+-doped La3Si8N11O4, the Eu2+-doped one shows a larger thermal quenching, predominantly owing to photoionization. Under 320 nm excitation, the internal and external quantum efficiencies are 44 and 33%, respectively.
RESUMO
BACKGROUND: Vitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale. METHODS: A meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed. RESULTS: A total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03-2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07-1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03-2.53; P = 0.04) and population who lived in middle latitude district (30-60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04-1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented). CONCLUSION: The results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.
Assuntos
Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Síndrome Metabólica/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Povo Asiático , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Síndrome Metabólica/etnologia , Síndrome Metabólica/patologia , Razão de Chances , Síndrome do Ovário Policístico/etnologia , Síndrome do Ovário Policístico/patologia , Pigmentação da Pele/genética , População BrancaRESUMO
Photoinduced reactions of ruthenium complexes with molecular oxygen have attracted a lot of experimental attention; however, the reaction mechanism remains elusive. In this work, we have used the density functional theory method to scrutinize the visible-light induced photooxidation mechanism of the ruthenium complex [Ru(II)-(bpy)2 (TMBiimH2 )](2+) (bpy: 2, 2-bipyridine and TMBiimH2 : 4, 5, 4, 5-tetramethyl-2, 2-biimidazole) initiated by the attack of molecular oxygen. The present computational results not only explain very well recent experiments, also provide new mechanistic insights. We found that: (1) the triplet energy transfer process between the triplet molecular oxygen and the metal-ligand charge transfer triplet state of the ruthenium complex, which leads to singlet molecular oxygen, is thermodynamically favorable; (2) the singlet oxygen addition process to the S0 ruthenium complex is facile in energy; (3) the chemical transformation from endoperoxide to epidioxetane intermediates can be either two- or one-step reaction (the latter is energetically favored). These findings contribute important mechanistic information to photooxidation reactions of ruthenium complexes with molecular oxygen. © 2016 Wiley Periodicals, Inc.
RESUMO
Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.