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1.
Cancer Lett ; 593: 216925, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38718887

RESUMEN

Alternative polyadenylation (APA), an important post-transcriptional regulatory mechanism, is aberrantly activated in cancer,but how APA functions in tumorigenesis remains elusive. We analyzed APA events in RNA-seq data in TCGA and reported 3'UTR alterations associated with esophageal squamous cell carcinoma (ESCC) patient prognosis and gene expression changes involving loss of tumor-suppressive miRNA binding sites. Moreover, we investigated the expression and function of cleavage and polyadenylation specific factor 3 (CPSF3), a key APA regulator in ESCC. By immunohistochemistry and qRT-PCR, we found that CPSF3 was highly expressed in ESCC tissues and associated with poor patient prognosis. Overexpression of CPSF3 enhanced, while knockdown of CPSF3 inhibited ESCC cell proliferation and migration in vitro and in vivo, as determined by colony formation, transwell assays and animal experiments. Iso-Seq and RNA-seq data analysis indicated that knockdown of CPSF3 favored use of the distal poly (A) site in the 3'UTR of Cornichon family AMPA receptor auxiliary protein 2 (CNIH2), resulting in a long-3'UTR CNIH2 isoform that produced less CNIH2 protein due to miR-125a-5p targeting and downregulating CNIH2 mRNA through a miR-125a-5p binding site in the long CNIH2 mRNA 3'UTR. Moreover, CPSF3-induced ESCC tumorigenicity was mediated by CNIH2. Taken together, CPSF3 promotes ESCC progression by upregulating CNIH2 expression through loss of miR-125a-5p-mediated CNIH2 repression through alternative splicing and polyadenylation of the CNIH2 mRNA 3'UTR.

2.
Tob Induc Dis ; 222024.
Artículo en Inglés | MEDLINE | ID: mdl-38204733

RESUMEN

INTRODUCTION: The multicenter CHAMPION study aimed to assess the impact of smoking cessation on post-operative complications (PCs) and smoking cessation patterns in Chinese patients undergoing lung surgery. METHODS: Patients undergoing elective lung surgery were prospectively enrolled from three major tertiary centers in China. Patients were categorized as smokers or quitters before surgery. Baseline characteristics and smoking status were analyzed. The incidence of PCs and pulmonary PCs (PPCs), smoking relapse rate, and causes within six months post-operatively were investigated. The questionnaire was conducted in all patients and 30 healthcare professionals (HCPs), regarding the awareness and effectiveness of smoking cessation methods. RESULTS: Of the 276 enrolled patients, 213 (77.2%) were smokers and 63 (22.8%) were quitters; 76.4% were diagnosed with primary lung cancer. PCs occurred in 13.8% of patients, with similar proportions in smokers (14.1%) and quitters (12.7%). PPCs occurred in 9.8% of patients with no significant differences between smokers and quitters (9.4% vs 11.1%, p=0.70). At six months, 9.2% of patients relapsed, with a lower rate in quitters compared to smokers (3.3% vs 11.0%, p=0.01). HCPs exhibited higher awareness of smoking cessation methods than patients. Perceived effectiveness of smoking cessation methods from the patients were low. CONCLUSIONS: In patients undergoing lung surgery with a low risk of PCs, active smoking does not significantly increase the risk of PCs or PPCs relative to quitters, suggesting that there is likely no need to postpone lung surgery for those who have not yet quit smoking. However, further large-scale studies are necessary to confirm these findings.

3.
Opt Express ; 31(23): 38255-38267, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38017936

RESUMEN

Squeezed light near an atomic resonance is beneficial for efficient atom-light quantum interfaces. It is desirable but challenging to directly generate in atoms due to excess noise from spontaneous emission and reabsorption. Here, we report on the use of energy-level modulation to actively control atomic coherence and interference in degenerate four-wave mixing (DFWM) and then to enhance the DFWM gain process for the generation of near-resonant squeezed twin beams. With this technique, we obtain a -2.6 dB intensity-difference squeezing detuned 100 MHz from the D1 F = 4 to F' = 4 transition of 133Cs.

4.
Biol Direct ; 18(1): 74, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37957698

RESUMEN

Cancer stemness and osteosarcoma (OS) malignant progression are closely associated. However, the molecular mechanisms underlying this association have not been fully demonstrated. Long noncoding RNAs (lncRNAs) are an intriguing class of widely prevalent endogenous RNAs involved in OS progression, the vast majority of which have not been characterized functionally. Here, we identified tumor promoter lncRNA WAC-AS1 to be highly expressed in OS tumors and associated with worse survival. Further analysis revealed that WAC-AS1 increased tumorsphere formation of OS cells and promoted metastasis, as confirmed by cell proliferation, transwell and wound healing assays. MiR-5047 was identified as a downstream target of WAC-AS1. Subsequently, based on bioinformatics analysis, RIP assay and luciferase reporter assay, SOX2 mRNA was verified as a target of miR-5047. WAC-AS1 enhanced OS cell proliferation and stemness via acting as a ceRNA by binding to miR-5047, thereby increasing SOX2 expression. In addition, SOX2 bound to the promoter region of WAC-AS1 and promoted its transcription, thereby forming a positive feedback loop to regulate OS malignancy. Taken together, our findings show WAC-AS1 is a tumor promoter and a key regulator of OS cell stemness and metastasis via a miR-5047/SOX2 axis.


Asunto(s)
Neoplasias Óseas , MicroARNs , Osteosarcoma , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Osteosarcoma/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Carcinógenos , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo
5.
Gerodontology ; 40(4): 523-525, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37971287

RESUMEN

BACKGROUND: Daily toothbrushing is a routine approach for helping to keep the oral cavity healthy. However, using a toothbrush as an ordinary oral hygiene habit can also lead to adverse events. CASE PRESENTATION: A 75-year-old man was referred by a periodontist for vestibular ulcerations with gingival defects. The patient reported no significant medical or social history, which might be associated with his symptoms. On examination, wide labio-buccal gingival defects, white attached gingiva and linear vestibular ulcerations were observed. With the help of the periodontist, a diagnosis of inappropriate toothbrushing-induced traumatic ulcerations was reasoned via an approach of aetiological elimination. The patient was put on a trial course of topical dexamethasone powder with lincomycin. The resolution of vestibular ulcerations was apparent after two weeks. He reported no similar oral ulcerations during the following nine years. CONCLUSION: To our knowledge, this is the first case reported in the literature of vestibular ulcerations with severe gingival defects caused by inappropriate toothbrushing. The establishment of a correct diagnosis needs a close collaboration between periodontists and oral medicine specialists. Instruction on correct toothbrushing, especially for older people can be beneficial.


Asunto(s)
Placa Dental , Gingivitis , Úlceras Bucales , Masculino , Humanos , Anciano , Cepillado Dental/efectos adversos , Encía , Higiene Bucal , Úlceras Bucales/inducido químicamente
6.
J Int Med Res ; 51(6): 3000605231178510, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37340717

RESUMEN

OBJECTIVE: To explore the intrinsic mechanism of the mammalian target of rapamycin (mTOR) pathway activation and promotion of neuronal axon growth. METHODS: Human neuroblastoma cells, SH-SY5Y, were induced with all-trans retinoic acid (ATRA; 10 µM for three days) which differentiated the cell line into a neuronal-like state. Immunohistochemical staining was used to detect the differentiation status of the neuronal-like cells. Phosphatase and tensin homolog (PTEN) RNA interference (RNAi) experiments were performed on the differentiated cells; reverse transcription-polymerase chain reaction (RT-PCR) detected transcriptional levels of PTEN following 24 h of interference. After 36 h, western blot assay was used to detect expression levels of ribosomal protein S6 kinase (pS6k) and mTOR. To downregulate the expression of PTEN and cluster of differentiation 44 (CD44), a cell-surface glycoprotein, simultaneously, PTEN siRNA and CD44 siRNA sequences were mixed in equal proportions in co-interference experiments. RT-PCR detected the transcription level of CD44, and the relationship between the CD44 and axonal growth was observed after 48 h of interference. RESULTS: Microtubule-associated protein 2 (MAP2) expression was enhanced after three days of induction in SH-SY5Y cells. RT-PCR showed the transcription level of PTEN was significantly downregulated after 24 h of PTEN knockdown. mTOR and pS6k protein expression levels were significantly upregulated after 36 h of interference. CD44 transcription levels were upregulated after PTEN gene interference. The neurite length of the cells in the experimental interference group was significantly longer than that in the control group, and the expression level of CD44 was positively correlated with neurite growth. The neurite length of the PTEN-only interference group was significantly greater than that of the co-interference and ATRA groups. CONCLUSION: Activation of the mTOR pathway promoted neurite growth through upregulation of CD44 expression, thus promoting neuronal regeneration.


Asunto(s)
Neuritas , Neuroblastoma , Humanos , Regulación hacia Arriba , Neuritas/metabolismo , Sirolimus , Neuroblastoma/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , ARN Interferente Pequeño/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Hialuranos/genética
7.
Exp Hematol Oncol ; 12(1): 48, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37218007

RESUMEN

Approximately 60-80% of cancer patients treated with abdominopelvic radiotherapy suffer post-radiotherapy toxicities including radiation enteropathy and myelosuppression. Effective preventive and therapeutic strategies are lacking for such radiation injury. The gut microbiota holds high investigational value for deepening our understanding of the pathogenesis of radiation injury, especially radiation enteropathy which resembles inflammatory bowel disease pathophysiology and for facilitating personalized medicine by providing safer therapies tailored for cancer patients. Preclinical and clinical data consistently support that gut microbiota components including lactate-producers, SCFA-producers, indole compound-producers and Akkermansia impose intestinal and hematopoietic radio-protection. These features serve as potential predictive biomarkers for radiation injury, together with the microbial diversity which robustly predicts milder post-radiotherapy toxicities in multiple types of cancer. The accordingly developed manipulation strategies including selective microbiota transplantation, probiotics, purified functional metabolites and ligands to microbe-host interactive pathways are promising radio-protectors and radio-mitigators that merit extensive validation in clinical trials. With massive mechanistic investigations and pilot clinical trials reinforcing its translational value the gut microbiota may boost the prediction, prevention and mitigation of radiation injury. In this review, we summarize the state-of-the-art landmark researches related with radio-protection to provide illuminating insights for oncologists, gastroenterologists and laboratory scientists interested in this overlooked complexed disorder.

8.
Molecules ; 28(5)2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36903510

RESUMEN

Recently, polyolefin thermoplastic elastomers can be obtained directly using ethylene as a single feedstock via α-diimine nickel-catalyzed ethylene chain walking polymerization. Here, a new range of bulky acenaphthene-based α-diimine nickel complexes with hybrid o-phenyl and -diarylmethyl anilines were constructed and applied to ethylene polymerization. All the nickel complexes under the activation of excess Et2AlCl exhibited good activity (level of 106 g mol-1 h-1) and produced polyethylene with high molecular weight (75.6-352.4 kg/mol) as well as proper branching densities (55-77/1000C). All the branched polyethylenes obtained exhibited high strain (704-1097%) and moderate to high stress (7-25 MPa) at break values. Most interestingly, the polyethylene produced by the methoxy-substituted nickel complex exhibited significantly lower molecular weights and branching densities, as well as significantly poorer strain recovery values (48% vs. 78-80%) than those by the other two complexes under the same conditions.

9.
Artículo en Inglés | MEDLINE | ID: mdl-36011899

RESUMEN

Recently, the rapid growth in vehicle activity in rapidly urbanized areas has led to the discharge of large amounts of polycyclic aromatic hydrocarbons (PAHs) into roadside soils and these compounds have gradually accumulated in the soil, which poses a serious threat to national food security and public health. However, previous studies did not clearly investigate the seasonal differences in PAH pollution of roadside soil by different highways. Therefore, based on field investigations, this study collected 84 soil surface samples to compare the pollution characteristics of 16 PAHs in farmland soils located near different roads in different seasons in Guangzhou, China. The results showed that the concentration of Σ16PAHs in farmland soils in spring (with a mean value of 258.604 µg/kg) was much higher than that in autumn (with a mean value of 157.531 µg/kg). There are differences in the PAH compositions in spring (4 ring > 3 ring > 5 ring > 6 ring) and autumn (4 ring > 5 ring > 6 ring > 3 ring). The proportion of 4−6 ring PAHs was much higher than 2−3 ring PAHs in both seasons. The spatial differences were significant. The sampling areas with higher concentrations of 16 PAHs were Tanbu Town, Huadu District (TB), Shitan Town, Zengcheng District (ST), and Huashan Town, Huadu District (HS), while the lowest concentration was in Lanhe Town, Nansha District (LH). The results of the diagnostic ratios showed that the main source of soil PAHs consists of a mixed source from petroleum and biomass combustion. The results from the total pollution assessment method and Nemerow index method indicated that the pollution levels of PAHs in the farmland soils indicated weak contamination. Our study provides a scientific basis for the prevention and control of soil pollution in farmlands near highways.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , China , Monitoreo del Ambiente/métodos , Granjas , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis
11.
Inorg Chem ; 61(18): 6799-6806, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-35476412

RESUMEN

The branching density of polyethylene generated in the α-diimine Pd(II) system is usually very high, largely independent of simple ligand modifications with steric or electronic perturbations, or the polymerization conditions. In this study, we designed and synthesized a class of bulky hybrid α-diimine Pd(II) catalysts combining ortho-diarylmethyl and ortho-phenyl moieties to explore the relationship between the polyethylene microstructure and the spatial structure of catalysts. In ethylene polymerization, the hybrid α-diimine Pd(II) catalysts exhibited high activities (well above 105 g·mol-1·h-1) and yielded highly branched (90-110/1000C) polyethylenes with high molecular weights (up to 278.3 kg/mol). Compared with the two corresponding symmetrical ortho-diarylmethyl-based or ortho-phenyl-based Pd(II) catalysts, the hybrid catalysts generated polyethylene of significantly higher branching densities (92 vs 28-34/1000C) in marked higher activities. Similar phenomena are also observed in the copolymerization of ethylene with polar monomers. Moreover, the hybrid Pd(II) catalysts can more efficiently promote the copolymerization of ethylene with various polar monomers in comparison to the corresponding symmetrical catalysts. The more open spatial environment around the metal center by using a hybrid steric strategy was proposed to be responsible for above advantages.

12.
J Exp Clin Cancer Res ; 41(1): 111, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35346324

RESUMEN

BACKGROUND: Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression. METHODS: PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession. RESULTS: PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10. CONCLUSION: PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas de la Membrana , MicroARNs , Proteína I de Unión a Poli(A) , Línea Celular Tumoral , Proliferación Celular/genética , Células Endoteliales/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , MicroARNs/genética , Proteína I de Unión a Poli(A)/metabolismo , ARN Mensajero , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
13.
Shanghai Kou Qiang Yi Xue ; 31(4): 414-417, 2022 Aug.
Artículo en Chino | MEDLINE | ID: mdl-36710557

RESUMEN

PURPOSE: To study on the accuracy of implant-borne single restoration by two production processes with Ti-base to provide experimental data for proper processes of single implant-borne restoration. METHODS: Thirty patients were selected with single posterior teeth missing from the Department of Oral Implantology of Shanghai Putuo District Eye Disease and Dental Disease Prevention and Treatment Institute. The patients were taken 2 traditional impressions clinically for two plaster model equipped with implant analogue. These models were then divided into 2 groups according to different production processes. The experimental group was scanned with the scan body installed in the model implant analogue, while the control group was scanned directly on the Ti-base abutment installed in the model implant analogue. The implant-borne single restorations of the two groups were cut along the buccal-lingual side and the distance between the measuring point to the Ti-Base abutment was observed by electron microscopy. In addition, the breaking limit of zirconia crown was observed, universal test machine was used to load direct force to the crown. SPSS 22.0 software package was used for data analysis. RESULTS: The gap between the implant-borne single restoration to the Ti-base abutment of the experimental group was significantly smaller than that of the control group. The difference between the two groups was statistically significant (P<0.05). However, by testing the breaking limit of zirconia crown, there was no significant difference(P>0.05). CONCLUSIONS: Using scan body to transfer the implant position and Ti-base abutment data information to the digital dental design software is more accurate and reliable than directly scanning the Ti-base on the model analogue. Using scan body is recommended for processing and manufacture of implant-borne singe restoration.


Asunto(s)
Diseño de Implante Dental-Pilar , Titanio , Humanos , China , Coronas , Circonio , Pilares Dentales , Fracaso de la Restauración Dental , Ensayo de Materiales , Análisis del Estrés Dental , Diseño Asistido por Computadora
14.
Shanghai Kou Qiang Yi Xue ; 31(4): 435-438, 2022 Aug.
Artículo en Chino | MEDLINE | ID: mdl-36710561

RESUMEN

PURPOSE: To investigate the effects of ultrasonic scaling and root planning(SRP) assisted by perioscope on gingival recession of maxillary lateral incisor. METHODS: Thirty-six outpatients with moderate to advanced chronic periodontitis from the Department of Periodontology at Dental and Ophthalmic Clinic of Putuo District from June 2020 to December 2020 were collected as research objects. Periodontal treatment was carried out according to a single-blind split-mouth self-control design randomly with(experimental group, namely perioscope group) or without(control group, namely SRP group) periodontal endoscope.The labial periodontal probing depth (PD), labial attachment loss (AL) and gingival recession(GR) in the maxillary lateral incisors were recorded at baseline, 3 and 6 months, and compared among groups by SPSS 22.0 software package. RESULTS: There was no significant difference between perioscope group and SRP group at baseline. ΔGR (the recession extent of gum within two observation time) in perioscope group was significantly smaller than that in SRP group at 3 months(P<0.05). There was no significant difference in other periodontal indicators at 3 and 6 months between the 2 groups after treatment, but it can be found that the degree of PD reduction and AL improvement in perioscope group was more than those in SRP group, this trend was most obvious at 3 months. PD and AL were significantly different between baseline and 3 months or 6 months in the two groups. There were significant differences in ΔGR at 3 months and 6 months between the two groups. CONCLUSIONS: Compared with routine SRP, the extent of root surface debridement with perioscope-assisted SRP is thorough and less invasive, and the reduction of gingival recession of labial surface of maxillary lateral incisor at 3 months is significantly less; thus, the aesthetic effect is prominent.


Asunto(s)
Recesión Gingival , Humanos , Raspado Dental , Estudios de Seguimiento , Recesión Gingival/terapia , Pérdida de la Inserción Periodontal/terapia , Bolsa Periodontal/terapia , Aplanamiento de la Raíz , Método Simple Ciego , Resultado del Tratamiento
15.
Mol Oncol ; 15(5): 1566-1583, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33660414

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is one of the most refractory malignancies worldwide. Mitogen-activated protein kinase 3 (MAP2K3) has a contradictory role in tumor progression, and the function and expression patterns of MAP2K3 in ESCC remain to be determined. We found that MAP2K3 expression to be downregulated in ESCC, and MAP2K3 downregulation correlated with clinically poor survival. MAP2K3 inhibited ESCC cell proliferation and invasion in vitro and in vivo. MAP2K3 suppressed STAT3 expression and activation. Mechanistically, MAPSK3 interacted with MDM2 to promote STAT3 degradation via the ubiquitin-proteasome pathway. Furthermore, exosomal miR-19b-3p derived from the plasma of patients with ESCC could suppress MAP2K3 expression to promote ESCC tumorigenesis. STAT3 was found to bind to the MIR19B promoter and increased the expression of miR-19b-3p in ESCC cells. In summary, our results demonstrated that the miR-19b-3p-MAP2K3-STAT3 feedback loop regulates ESCC tumorigenesis and elucidates the potential of therapeutically targeting this pathway in ESCC.


Asunto(s)
Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , MAP Quinasa Quinasa 3/fisiología , MicroARNs/fisiología , Factor de Transcripción STAT3/fisiología , Adulto , Anciano , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Retroalimentación Fisiológica/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MAP Quinasa Quinasa 3/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Factor de Transcripción STAT3/genética
16.
Theranostics ; 11(3): 1473-1492, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391546

RESUMEN

Background: Collagen type VI alpha 1 (COL6A1) has been found to be dysregulated in several human malignancies. However, the role of COL6A1 in osteosarcoma (OS) progression remains largely unclear. Here, we aimed to explore the clinical significance and biological involvement of COL6A1 in the OS cell migration and invasion. Material and Methods: We used immunohistochemistry, qRT-PCR and western blot to detect the expression of COL6A1 in 181 OS patient samples. Chromatin immunoprecipitation (ChIP) and PCR were carried out to verify the regulatory interaction of p300, c-Jun and COL6A1 promoter. The invasion and migration function of COL6A1 in OS was detected in vitro and in vivo. RNA sequence was performed to detect the downstream pathway of COL6A1, and then co-immunoprecipitation (co-IP), ubiquitination assays and rescue experiments were performed to determine the regulatory effect of COL6A1 and signal transducers and activators of transcription (STAT1). Exosomes derived from OS cell lines were assessed for the ability to promote cancer progression by co-cultured assay and exosomes tracing. Results: COL6A1 was commonly upregulated in OS tissues, especially in lung metastasis tissues, which was associated with a poor prognosis. c-Jun bound p300 increased the enrichment of H3K27ac at the promoter region of the COL6A1 gene, which resulted in the upregulation of COL6A1 in OS. Overexpression of COL6A1 promoted OS cell migration and invasion via interacting with SOCS5 to suppress STAT1 expression and activation in an ubiquitination and proteasomal degradation manner. Most interestingly, we found that exosomal COL6A1 derived from OS cells convert normal fibroblasts to cancer-associated fibroblasts (CAFs) by secreting pro-inflammatory cytokines, including IL-6 and IL-8. The activated CAFs could promote OS cell invasion and migration by mediating TGF-ß/COL6A1 signaling pathway. Conclusion: Our data demonstrated that upregulation of COL6A1 activated by H3K27 acetylation promoted the cell migration and invasion by suppressing STAT1 pathway in OS cells. Moreover, COL6A1 can be packaged into OS cell-derived exosomes and activate CAFs to promote OS metastasis.


Asunto(s)
Colágeno Tipo VI/metabolismo , Histonas/metabolismo , Neoplasias Pulmonares/metabolismo , Osteosarcoma/metabolismo , Factor de Transcripción STAT1/metabolismo , Acetilación , Adolescente , Adulto , Anciano , Animales , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Niño , Exosomas/metabolismo , Exosomas/patología , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Osteosarcoma/patología , Transducción de Señal/fisiología , Regulación hacia Arriba/fisiología , Adulto Joven
17.
Biomark Res ; 8: 18, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32514351

RESUMEN

Chimeric antigen receptor (CAR) T cell therapy, especially anti-CD19 CAR T cell therapy, has shown remarkable anticancer activity in patients with relapsed/refractory acute lymphoblastic leukemia, demonstrating an inspiring complete remission rate. However, with extension of the follow-up period, the limitations of this therapy have gradually emerged. Patients are at a high risk of early relapse after achieving complete remission. Although there are many studies with a primary focus on the mechanisms underlying CD19- relapse related to immune escape, early CD19+ relapse owing to poor in vivo persistence and impaired efficacy accounts for a larger proportion of the high relapse rate. However, the mechanisms underlying CD19+ relapse are still poorly understood. Herein, we discuss factors that could become obstacles to improved persistence and efficacy of CAR T cells during production, preinfusion processing, and in vivo interactions in detail. Furthermore, we propose potential strategies to overcome these barriers to achieve a reduced CD19+ relapse rate and produce prolonged survival in patients after CAR T cell therapy.

18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(6): 612-616, 2018 12 25.
Artículo en Chino | MEDLINE | ID: mdl-30900839

RESUMEN

OBJECTIVE: To sum up experience in unibody bifurcation stent graft in the treatment of abdominal aortic aneurysm with aortic bifurcation stenosis. METHODS: Clinical data of 19 cases of abdominal aortic aneurysm and aortic bifurcation stenosis received endovascular treatment using unibody bifurcation stent graft in Zhejiang Provincial People's Hospital during March 2009 and March 2018 were collected. The clinical characteristics, surgery procedure and follow-up results were reviewed. RESULTS: Stent graft was successful in all patients, and the average operation time was (70.0±2.3) min. Leakage was found in 3 patients, in which 2 patients with type Ⅰ leakage and 1 patient with type Ⅱ leakage. All leakage disappeared 15 days after surgery. The 19 cases were followed-up for 9-48 months with the median follow-up time of 27 months, and no displacement, leakage and lower limb ischemia was observed. CONCLUSIONS: Unibody bifurcation stent graft is of satisfactory long-term effect for patients with abdominal aortic aneurysm and aortic bifurcation stenosis, and can avoid displacement of stent graft after operation.


Asunto(s)
Aneurisma de la Aorta Abdominal , Estenosis de la Válvula Aórtica , Implantación de Prótesis Vascular , Stents , Aneurisma de la Aorta Abdominal/cirugía , Estenosis de la Válvula Aórtica/cirugía , Humanos , Resultado del Tratamiento
19.
Shanghai Kou Qiang Yi Xue ; 26(3): 317-320, 2017 Jun.
Artículo en Chino | MEDLINE | ID: mdl-29098255

RESUMEN

PURPOSE: To investigate the effect and safety of two techniques of immediate implants on the length of alveolar bone as well as the soft and hard tissue in the anterior maxillary zone. METHODS: One hundred and sixty cases of immediate implants in anterior maxillary zone were collected from August 2014 to August 2015 in our hospital. They were randomly and equally divided into flap group (80 cases) and flapless group (80 cases). The former received flap immediate implant while the later received flapless therapy. A 1-year follow-up, comparison on alveolar bone length, soft tissue and complications was carried out and the results were recorded. The data were analyzed with SPSS 17.0 software package. RESULTS: The number of surviving implants with flap was 63 and the survival rate was 97.5%, while the number of the surviving implants in the flapless group was 63 with survival rate being 78.75% (P<0.05). Patients in both groups had pain, bleeding, edema and other complications. The incidence rate of complications of flapless group was 11.25%, 6.25%, 8.75% respectively and the total rate was 26.25% while that of the flap group was 23.75%, 16.25%, 20%, respectively, and the total rate was 60% (P<0.05) .The depth of gingival sulcus between the two groups had no significant difference after treatment (P>0.05). The alveolar bone crest absorption and length decreased after implantation, meanwhile, there was also significant difference between the two groups after implantation (P<0.05). CONCLUSIONS: Immediate dental implantation without flap can reduce the length of the alveolar bone and operative complications and improve the contour and physiological condition of soft and hard tissue more than that with flap.


Asunto(s)
Proceso Alveolar , Implantación Dental Endoósea , Prótesis Dental de Soporte Implantado , Colgajos Quirúrgicos , Pérdida de Hueso Alveolar , Proceso Alveolar/cirugía , Implantes Dentales , Encía , Humanos , Resultado del Tratamiento
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