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The quantitative detection of antibodies is crucial for the diagnosis of infectious and autoimmune diseases, while the traditional methods experience high background signal noise and restricted signal gain. In this work, we have developed a highly efficient electrochemical biosensor by constructing a programmable DNA nanomachine integrated with electrochemically controlled atom transfer radical polymerization (eATRP). The sensor works by binding the target antidigoxin antibody (anti-Dig) to the epitope of the recognization probe, which then initiates the cascaded strand displacement reaction on a magnetic bead, leading to the capture of cupric oxide (CuO) nanoparticles through magnetic separation. After CuO was dissolved, the eATRP initiators were attached to the electrode based on the CuΙ-catalyzed azide-alkyne cycloaddition. The subsequent eATRP reaction results in the formation of long electroactive polymers (poly-FcMMA), producing an amplified current response for sensitive detection of anti-Dig. This method achieved a detection limit at clinically relevant picomolar concentration in human serum, offering a sensitive, convenient, and cost-effective tool for detecting various biomarkers in a wide range of applications.
Assuntos
Anticorpos , Técnicas Biossensoriais , Cobre , DNA , Técnicas Eletroquímicas , Polimerização , DNA/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Humanos , Anticorpos/imunologia , Anticorpos/química , Cobre/química , Limite de DetecçãoRESUMO
BACKGROUND: Abnormal N6-methyladenosine (m6A) modification has become a driving factor in tumour development and progression. The linc00659 is abnormally highly expressed in digestive tract tumours and promotes cancer progression, but there is little research on the mechanism of linc00659 and m6A. METHODS: The expression of linc00659 in colorectal cancer (CRC) tissues and cells was assessed by a quantitative real-time PCR. The proliferative capacity of CRC cells was determined by colony formation, Cell Counting Kit-8 and 5-ethynyl-2 deoxyuridine assays, and the migratory capacity of CRC was determined by wound healing and transwell assays and tube formation. In vivo, a xenograft tumour model was used to detect the effect of linc00659 on tumour growth. The Wnt/ß-catenin signalling pathway and related protein expression levels were measured by western blotting. The binding of linc00659 to insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by RNA pull-down and an immunoprecipitation assay. The effect of IGF2BP1 on FZD6 was detected by an RNA stability assay. RESULTS: The expression of linc00659 was abnormally elevated in CRC tissues and cells compared to normal colonic tissues and cells. We confirm that linc00659 promotes the growth of CRC cells both in vivo and in vitro. Mechanistically, linc00659 binds to IGF2BP1 and specifically enhances its activity to stabilize the target gene FZD6. Therefore, linc00659 and IGF2BP1 activate the Wnt/ß-catenin signalling pathway, promoting cell proliferation in CRC. CONCLUSIONS: Our results show that linc00659 and IGF2BP1 cooperate to promote the stability of the target FZD6 mRNA, thereby facilitating CRC progression, which may represent a potential diagnostic, prognostic and therapeutic target for CRC.
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Adenina , Neoplasias Colorretais , RNA Longo não Codificante , Via de Sinalização Wnt , Animais , Humanos , Adenina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA MensageiroRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) play a critical role in regulating various human diseases including cancer. In colorectal cancer (CRC), there are still some undervalued lncRNAs with potential functions and mechanisms that need to be clarified. The present study aimed to investigate the role of linc02231 in the progression of CRC. METHODS: The proliferation of CRC cells was evaluated using Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell migration was examined through wound healing and Transwell analyses. The impact of linc02231 on angiogenesis was determined through a tube formation assay. Western blotting was used to detect the expression of specific proteins. A mouse xenograft model is established to observe the effect of linc02231 on the in vivo growth of CRC cells. Target genes of linc02231 are screened using high-throughput sequencing. The transcriptional activity of STAT2 on linc02231 and the binding activity between linc02231/miR-939-5p/hnRNPA1 were analyzed by a luciferase assay. RESULTS: Based on public databases and comprehensive bioinformatics analysis, we found that lncRNA linc02231 was upregulated in CRC tumor tissues, which is consistent with our clinical results. linc02231 promoted the proliferation and migration of CRC cells in vitro and their tumorigenicity in vivo. Furthermore, linc02231 promotes the angiogenic ability of human umbilical vein endothelial cells. Mechanistically, the transcription factor STAT2 binds to the promoter region of linc02231 and activates its transcription. linc02231 also competes with miR-939-5p for binding to the pro-oncogenic target gene hnRNPA1, preventing its degradation. hnRNPA1 prevents the maturation of angiopoietin-like protein 4 (ANGPTL4) messenger RNA, leading to impaired tumor angiogenesis and increased metastasis of CRC. CONCLUSIONS: The expression of linc02231, which is induced by STAT2, has been found to enhance the proliferation, metastasis, and angiogenesis of CRC by binding to miR-939-5p and increasing the expression of hnNRPA1 at the same time as suppressing ANGPTL4. These findings suggest that linc02231 could serve as a potential biomarker and therapeutic target for CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Proteína 4 Semelhante a Angiopoietina/metabolismo , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Surgical techniques and graft materials are important factors for short nose lengthening in both primary and revision rhinoplasty in Asian patients. Other subunit of the nose need to be improved as well to achieve aesthetic perfection. MATERIALS AND METHODS: A cohort of 98 patients who underwent primary and revision rhinoplasty for moderate to severe short nose deformity from January 1, 2019, to December 31, 2020, were enrolled. Nasal elongation was achieved via an open rhinoplasty approach using autologous costal cartilage exclusively for grafting. Aesthetic outcomes were evaluated by anthropometric measurement and satisfaction assessment from patients and physicians. RESULTS: The mean duration of follow-up was 10.6 months. In both primary and revision cases, nasal length relative to preoperative measurements increased significantly, while nasal tip projection did not differ significantly. Columellar-facial angle and nasofrontal angle decreased significantly in both groups. Both physicians and patients reported improvement in aesthetic outcomes. CONCLUSIONS: Aesthetic satisfaction was reported from both patients and physicians. Autologous costal cartilage is an ideal graft material that offers strong structural support. Caudal septal extension graft using autologous costal cartilage sandwiched by extended spreader grafts achieve satisfactory lengthening of the central compartment and also increase nasal tip projection and rotation.
Assuntos
Deformidades Adquiridas Nasais , Rinoplastia , Humanos , Rinoplastia/métodos , Deformidades Adquiridas Nasais/cirurgia , Estética Dentária , Nariz/cirurgia , Septo Nasal/cirurgia , ReoperaçãoRESUMO
Oxaliplatin resistance inevitably occurs in almost all cases of metastatic colorectal cancer (CRC), and it is important to study the roles of lncRNAs and their specific regulatory mechanisms in oxaliplatin resistance. Exosomes are increasingly designed for drug or functional nucleic acid delivery due to their properties, thereby improving the effectiveness of cancer therapy. The results of this study show that the low expression of PGM5 antisense RNA 1 (PGM5-AS1) in colon cancer is induced by transcription inhibitor, GFI1B. PGM5-AS1 prevents proliferation, migration, and acquired oxaliplatin tolerance of colon cancer cells. Exosomes encapsulating oxaliplatin and PGM5-AS1 can reverse drug resistance. For identifying differentially expressed target genes regarding PGM5-AS1, RNA transcriptome sequencing was performed. The mechanism by which PGM5-AS1 regulates its target genes was explored by performing experiments such as fluorescent in situ hybridization assay, dual-luciferase reporter gene assay, and RNA immunoprecipitation. The results show that by recruiting SRSF3, PGM5-AS1 activates alternate splicing to downregulate PAEP expression. For hsa-miR-423-5p, PGM5-AS1 can also act as a sponge to upregulate the NME1 expression.
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Neoplasias do Colo , Exossomos , MicroRNAs , RNA Longo não Codificante , Proliferação de Células/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Resistência a Medicamentos , Exossomos/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , MicroRNAs/metabolismo , Oxaliplatina/farmacologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismoRESUMO
ABSTRACT: Rhinoplasty to reshape the nasal tip is increasingly popular among Chinese women. Aesthetic standards vary across different ethnic groups and it is key to identify preferences for the ideal nasal tip in China to set surgical goals. Therefore, we administered an online survey to plastic surgeons and the public through social media to rank nasal tip images by aesthetic preference. Images were created from a single photograph to show various dimensions of nasal tip projection to nasal dorsum length ratio (NTP/NDL) and nasal labial angle (NLA). Preferences were compared by age, sex, living area, ethnic background, occupation, and history of plastic procedures on respondents' preferences. Overall, there were 703 respondents, including 441 (63%) women and 50 plastic surgeons. Nasal tip projection to nasal dorsum length ratio of 0.63 was ranked highest by all demographic groups, including women (47%), men (50%), and plastic surgeons (66%). Nasal labial angle of 106° was first choice overall and preferred by 34%, 34%, and 52%, respectively. Preferences followed a bell curve for NTP/NDL and NLA, with lower rates of preference as parameters diverged further from the first choice. The preference for NTP/NDL of 0.63 and NLA of 106° was conserved across surgeons, lay people, and all demographic groups. The authors suggest that these proportions could be used as reference for preoperative design in rhinoplasty.
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Estética Dentária , Rinoplastia , Povo Asiático , Feminino , Humanos , Masculino , Nariz/cirurgia , Inquéritos e QuestionáriosRESUMO
ABSTRACT: In recent years, more Chinese surgeons have left other fields to enter plastic surgery. The factors influencing this respe-cialization have not been elicited. The authors aim to elucidate Chinese surgeons' experience and career satisfaction in this specialty change. Between July and September 2020, the authors conducted an online survey of nonplastic surgeons who received plastic surgery training at an academic center. The survey evaluated their motivation for pursuing their field, practice patterns, and career satisfaction. Responses were compared those who respecialized in plastic surgery with those who did not. A total of 251 nonplastic surgeons completed the survey. The most frequent reasons for pursuing plastic surgery were lifestyle (61.1%), desire to help others (44.4%), and higher compensation (37.3%). Among those who changed fields, employment in academic centers declined from 85% to 51.7%, 70% devoted at least half of their practice to aesthetic surgery, and the median nights on call decreased from 1.54 to 0.38 per week after specializing in plastic surgery. Overall career satisfaction in plastic surgery was significantly higher compared with their former specialties (78.3% versus 28.3%, P 0.05). The authors' study showed that outflow of surgeons from other specialties to plastic surgery is mainly due to burnout, which erodes physicians' satisfaction level and the quality of care they are able to provide. The authors highlight the need for reducing burnout in other surgical fields as well as rigorous plastic and aesthetic surgery training for those changing fields to ensure high-quality patient care.
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Esgotamento Profissional , Cirurgiões , Cirurgia Plástica , Povo Asiático , China , Humanos , Satisfação no Emprego , Cirurgia Plástica/educação , Inquéritos e QuestionáriosRESUMO
Augmentation rhinoplasty has gained popularity in China in the past decades and nasion profile is a key variable in aesthetic outcomes. The nasion is the deepest portion of the nasofrontal groove and its aesthetic preferences vary between different ethnic groups. At the time of this writing, there is limited research about ideal nasion measurements in the Chinese population. Therefore, we conducted an online survey of plastic surgeons and the public through social media. Participants were asked to rank nasion images according to their preferences. Images were created from a 3-dimensional scan of a Chinese Han female and modified to show various dimensions of nasion height, position, and forehead height. Nasion preferences were compared by age, sex, ethnicity, occupation, and whether had a history of plastic surgery. There were 777 respondents, including 461 (59.3%) women and 74 (9.5%) plastic surgeons. Nasion height of 8 and 10 mm ranked highest among all demographic groups. All respondents preferred nasion position to be level with the center of the pupil and forehead height of 4 mm above the nasion. Our study showed that the ideal Chinese nasion is in line with baseline ethnic characteristics. Therefore, plastic surgeons must be aware of these nasion preferences to guide preoperative discussions and achieve satisfactory outcomes.
Assuntos
Rinoplastia , Cirurgia Plástica , Humanos , Feminino , Masculino , Estética Dentária , Rinoplastia/métodos , Povo Asiático , EtnicidadeRESUMO
There is a need for a specialist pathway or progression in esthetic medicine for esthetic physicians. A structured program for specialized training in nonsurgical facial esthetics to empower physicians is the need of the hour. The pharmaceutical companies currently provide training sessions, taking considerable initiatives to train esthetic professionals. "Leaders of the future" is a global thought leadership program by the Allergan Aesthetics. The program was designed to support and nurture the next generation of leaders by focusing on science and evidence. It aimed to help practitioners grow, evolve, learn, share, and connect with leading international experts. The sessions were focused on the importance of science and sensibility in esthetic medicine, as well as critical thinking and leadership skills. Mentorship is one of the most effective approaches for transforming the lives of young esthetic practitioners and, in turn, future patients. In addition, the importance of in-depth knowledge of injection anatomy for safe practice was emphasized. As esthetic surgeons and physicians, we must commit to incorporating evidence-based medicine into our life-long practice. "Leaders of the Future" program aims to build a solid foundation for esthetic surgeons and physicians to grow and evolve as thought leaders. The program would also aid in the pursuit of a best esthetic practice that incorporates professional identity formation, clinical competence, and evidence-based management in nonsurgical esthetics.
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BACKGROUND: LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. METHODS: We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. RESULTS: AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. CONCLUSIONS: We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/genética , Regulação para Cima , Animais , Neoplasias dos Ductos Biliares/genética , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de NeoplasiasRESUMO
New developments in artificial intelligence (AI) offer opportunities to enhance plastic surgery practice, research, and education. In this article, we review relevant AI tools and applications, including machine learning, reinforcement learning, and natural language processing. Our own Markov decision process for keloid treatment illustrates how these models are developed and can be used to enhance decision-making in clinical practice. Finally, we discuss challenges of implementing AI and knowledge gaps that must be addressed to successfully apply AI in plastic surgery. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Queloide , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Inteligência Artificial , Medicina Baseada em Evidências , HumanosRESUMO
Colorectal cancer (CRC) is the third most common malignancy in the world, and long noncoding RNA (lncRNA) plays a critical role in carcinogenesis. Here, we report a novel lncRNA, MAPKAPK5-AS1, that acts as a critical oncogene in CRC. In addition, we attempted to explore the functions of MAPKAPK5-AS1 on tumor progression in vitro and in vivo. Quantitative RT-PCR was used to examine the expression of MAPKAPK5-AS1 in CRC tissues and cells. Expression of MAPKAPK5-AS1 was significantly upregulated in 50 CRC tissues, and increased expression of MAPKAPK5-AS1 was found to be associated with greater tumor size and advanced pathological stage in CRC patients. Knockdown of MAPKAPK5-AS1 significantly inhibited proliferation and caused apoptosis in CRC cells. We also found that p21 is a target of MAPKAPK5-AS1. In addition, we are the first to report that MAPKAPK5-AS1 plays a carcinogenic role in CRC. MAPKAPK5-AS1 is a novel prognostic biomarker and a potential therapeutic candidate for CRC cancer.
Assuntos
Proliferação de Células/genética , Neoplasias Colorretais/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Células HCT116 , Células HT29 , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Interferência de RNA , Terapêutica com RNAi/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. Current evidence has revealed the key roles of long non-coding RNAs (IncRNAs) in multiple cancers, including CRC. In this study we identified the lncRNA SH3PXD2A-AS1 as a novel molecule associated with CRC progression by analyzing the publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine the expression levels of SH3PXD2A-AS1 in CRC tissue samples and CRC cell lines. Cell viability examination, colony-formation experiments, ethynyl deoxyuridine (Edu) assays and flow cytometry were performed to investigate the roles of SH3PXD2A-AS1 in CRC proliferation, cell cycle regulation, and apoptosis. Transwell assays were used to explore the effects of SH3PXD2A-AS1 on CRC cells migration and invasion. A nude mice model was used to assess the effects of SH3PXD2A-AS1 on tumorigenesis in vivo. Subcellular fractionation, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays were conducted to detect the molecular mechanisms of SH3PXD2A-ASl-mediated gene expression. Rescue assays were used to determine whether P57 and Kruppel-like factor 2 (KLF2) were involved in SH3PXD2A-ASl-dependent CRC proliferation. RESULTS: We firstly found that SH3PXD2A-AS1 was significantly upregulated in CRC tissues and cell lines, and overexpression of SH3PXD2A-AS1 was correlated with tumor size, TNM stage, and lymph node metastasis in patients with CRC. Furthermore, SH3PXD2A-AS1 knockdown inhibited CRC cells proliferation, migration and invasion in vitro, and suppressed tumorigenesis in vivo. Mechanistic studies indicated that SH3PXD2A-AS1 could epiqenetically repress P57 and KLF2 expression through interaction with EZH2. Rescue experiments suggested that SH3PXD2A-ASl-mediated oncogenesis was impaired by overexpression of P57 or KLF2. Interestingly, the expression of SH3PXD2A-AS1 was inversely correlated with the expression of P57 and KLF2 in CRC tissue samples. CONCLUSION: Our research presents the first evidence that SH3PXD2A-AS1 acts as an oncogene in CRC, and may be a promising diagnostic or therapeutic target in patients with CRC.
Assuntos
Neoplasias Colorretais/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , RNA Longo não Codificante/genética , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Progressão da Doença , Epigênese Genética , Feminino , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologiaRESUMO
Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), an enhancer of zeste homolog 2 (EZH2), IRAIN reduced PC tumor cell apoptosis and induced growth arrest by silencing the expression of Kruppel-like factor 2 (KLF2) and P15. Moreover, IRAIN expression was inversely correlated with that of KLF2 and P15 in PC tissues. To our knowledge, this is the first report elucidating the role and mechanism of IRAIN in PC progression.
Assuntos
Apoptose/genética , Proliferação de Células/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histona Desmetilases/metabolismo , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/biossíntese , Inibidor de Quinase Dependente de Ciclina p15/genética , Feminino , Humanos , Fatores de Transcrição Kruppel-Like/biossíntese , Fatores de Transcrição Kruppel-Like/genética , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Interferência de RNA , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.
Assuntos
Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Inativação Gênica , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , Animais , Apoptose , Western Blotting , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR. RESULTS: SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (-) breast carcinoma cells. CONCLUSIONS: SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.
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Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , RNA Longo não Codificante/genética , Regulação para Cima/genética , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Pessoa de Meia-IdadeRESUMO
In this paper, we propose a new method for protein detection by making use of magnetic graphene for enrichment and separation of the targets and duplex DNA-templated copper nanoparticles for amplification of electrochemical signals. Because the binding of the target protein (e.g. folate receptor) and small molecule (e.g. folate) can protect complementary DNA (cDNA) from exonuclease III-catalyzed degradation, duplex DNA from the hybridization of probe DNA and cDNA can act as the template for the formation of copper nanoparticles (CuNPs). Afterward, CuNPs-coated DNA can be enriched on the surface of magnetic graphene through the 3'-overhanging end of probe DNA, and then separated from the reaction mixture with the aid of magnet. As a result, copper ions released from acid-dissolution of CuNPs can catalyze the oxidation of o-phenylenediamine (OPD) by dissolved oxygen, resulting in an amplified electrochemical response. Our method can sensitively detect target protein over a wide linear range and with a low detection limit of 7.8 pg mL(-1), which can easily distinguish the targets even in complex serum samples. Therefore, this method may be promising for the clinical diagnosis of protein biomarkers by changing the recognition elements in the future.
Assuntos
Técnicas Biossensoriais/métodos , Cobre/química , Técnicas Eletroquímicas/métodos , Receptores de Folato com Âncoras de GPI/sangue , Grafite/química , Imãs/química , Nanopartículas Metálicas/química , Animais , Bovinos , Sondas de DNA/química , DNA Complementar/química , Receptores de Folato com Âncoras de GPI/análise , Humanos , Limite de Detecção , Hibridização de Ácido NucleicoRESUMO
OBJECTIVE: There have been inconsistent results published regarding the relationship between dyslipidaemia and an increased risk of colorectal neoplasia (CRN), including colorectal adenoma (CRA) and colorectal cancer (CRC). We conducted a meta-analysis to explore the relationship between dyslipidaemia and CRN. DESIGN: We identified studies by performing a literature search using PubMed, EMBASE and the Science Citation Index through October 2013. SETTING: We analysed thirty-three independent studies reporting the association between CRN and at least one of the selected lipid components, including total cholesterol (TC), TAG, HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C). SUBJECTS: CRN cases (n 21 809) were identified. RESULTS: Overall, people with high levels of serum TAG (risk ratio (RR)=1.08; 95% CI 1.05, 1.12, P<0.00001) and LDL-C (RR=1.07; 95% CI 1.00, 1.14, P=0.04) presented an increased prevalence of CRN. Subgroup analyses revealed that high levels of serum TC (RR=1.04; 95% CI 1.01, 1.09, P=0.02), TAG (RR=1.06; 95% CI 1.03, 1.10, P=0.0009) and LDL-C (RR=1.11; 95% CI 1.04, 1.19, P=0.003) increased the risk of CRA but not of CRC. No association between serum HDL-C and risk for CRN (including CRA and CRC) was observed. CONCLUSIONS: Both TAG and LDL-C were significantly associated with an increasing prevalence of CRN. High levels of serum TC, TAG and LDL-C were positively associated with CRA but not with CRC. No significant association was observed between levels of serum HDL-C and CRN.
Assuntos
Adenoma/etiologia , Neoplasias Colorretais/etiologia , Dislipidemias/fisiopatologia , Adenoma/sangue , Adenoma/epidemiologia , Adulto , Colesterol/sangue , LDL-Colesterol/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Humanos , Hipercolesterolemia/fisiopatologia , Hipertrigliceridemia/fisiopatologia , Incidência , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Triglicerídeos/sangueRESUMO
BACKGROUND: Breast cancer remains a major health problem worldwide, and is becoming increasingly resistant to traditional drug treatments. For instance, Adriamycin (ADR) is beneficial for the treatment of breast cancer. However, its wide application often leads to drug resistance in clinic practice, which results in treatment failure. Gambogenic acid (GNA), a polyprenylated xanthone isolated from the traditional medicine gamboge, has been reported to effectively inhibit the survival and proliferation of cancer cells. Its effects on ADR resistance have not yet been reported in breast cancer. In this study, we examined the ability of GNA to modulate ADR resiatance and the molecular mechanisms underlying this process using a cell based in vitro system. METHODS: An MTT assay was used to evaluate the inhibitory effect of the drugs on the growth of MCF-7 and MCF-7/ADR cell lines. The effects of drugs on apoptosis were detected using Annexin-V APC/7-AAD double staining. The expression of apoptosis-related proteins and the proteins in the PTEN/PI3K/AKT pathway were evaluated by Western blot analysis. RESULTS: In the MCF-7/ADR cell lines, the IC50 (half maximal inhibitory concentration) of the group that received combined treatment with GNA and ADR was significantly lower than that in the ADR group, and this value decreased with an increasing concentration of GNA. In parallel, GNA treatment increased the chemosensitivity of breast cancer cells to ADR. The cell apoptosis and cell cycle anaysis indicated that the anti-proliferative effect of GNA is in virtue of increased G0/G1 arrest and potentiated apoptosis. When combined with GNA in MCF-7/ADR cell lines, the expression levels of the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) and the apoptosis-related proteins caspase-3 and capsese-9 were significantly increased, while the expression of phosphorylated AKT was decreased. CONCLUSIONS: Our study has indicated a potential role for GNA to increase the chemosensitivity of breast cancer cells to ADR. This modulatory role was mediated by suppression of the PTEN/PI3K/AKT pathway that led to apoptosis in MCF-7/ADR cells. This work suggests that GNA may be used as a regulatory agent for treating ADR resistance in breast cancer patients.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Xantenos/farmacologia , Antineoplásicos/química , Doxorrubicina/química , Feminino , Humanos , Células MCF-7 , Xantenos/químicaRESUMO
BACKGROUND: The axillary approach is the dominant incision used in China for breast augmentation. Systematic preoperative education regarding incision locations for breast augmentation is scarce in China. In this study, we surveyed Chinese patients to ascertain their preferences and concerns for incision location based on a comprehensive understanding of different incisions. METHODS: We used a literature review, patient interviews, and expert panels to develop the preoperative education material and questionnaire regarding different incision locations. The respondents were requested to choose one incision location before and after they received the preoperative education. Their initial choices and final decisions as well as the reasons for these choices were recorded and analyzed. Multinomial logistic regression was preformed to analyze the affecting factors on the incision choice. RESULTS: A total of 216 Chinese women participated in the study between 2012.5 and 2014.1. Initially, 176 (81.48%) women chose axillary incision, 27 (12.50%) chose periareolar incision, and 13 (6.02%) chose inframammary fold (IMF) incision. After they received preoperative education on incisions, the axillary and periareolar approaches decreased to 117 (54.17%) and 13 (6.02%), respectively, while IMF increased to 86 (39.81%). The easily hidden scar (43.98%), lower capsular contracture rate (23.15%), and lower possibility of injury to the breast parenchyma (17.13%) ranked as the top 3 reasons for the incision choice. Patients with a preoperative cup size of AA were 12.316 times more likely to choose the axillary approach relative to the IMF approach compared with those with a B cup (P = 0.044; 95% confidence interval [CI] 1.069-141.923). For each one-unit increase in BMI, the odds that a patient would choose the axillary versus the periareolar approach decreased by 32.4% (P = 0.049; 95% CI 0.457-0.999). CONCLUSIONS: The systematic and objective preoperative education material and questionnaire regarding different incision locations helped the Chinese patients make truly informed decisions and express their personal requirements. The axillary approach was the first option for more than half of Chinese women mainly because an easily hidden scar was considered the primary concern during the decision-making process. The patients with a low BMI and a small preoperative breast cup size were more likely to choose an axillary incision. However, a considerable number of Chinese women would choose the IMF incision and value its superiority in terms of a lower capsular contracture rate, less tissue trauma, and lower possibility of injury to the breast parenchyma. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.