RESUMO
MYB is a key regulator of hematopoiesis and erythropoiesis, and dysregulation of MYB is closely involved in the development of leukemia, however the mechanism of MYB regulation remains still unclear so far. Our previous study identified a long noncoding RNA (lncRNA) derived from the -34 kb enhancer of the MYB locus, which can promote MYB expression, the proliferation and migration of human leukemia cells, and is therefore termed MY34UE-AS. Then the interacting partner proteins of MY34UE-AS were identified and studied in the present study. hnRNPA0 was identified as a binding partner of MY34UE-AS through RNA pulldown assay, which was further validated through RNA immunoprecipitation (RIP). hnRNPA0 interacted with MY34UE-AS mainly through its RRM2 domain. hnRNPA0 overexpression upregulated MYB and increased the proliferation and migration of K562 cells, whereas hnRNPA0 knockdown showed opposite effects. Rescue experiments showed MY34UE-AS was required for above mentioned functions of hnRNPA0. These results reveal that hnRNPA0 is involved in leukemia through upregulating MYB expression by interacting with MY34UE-AS, suggesting that the hnRNPA0/MY34UE-AS axis could serve as a potential target for leukemia treatment.
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Proliferação de Células , Leucemia , Proteínas Proto-Oncogênicas c-myb , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Elementos Facilitadores Genéticos , Regulação Leucêmica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Células K562 , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) was one of the most prevalent life-threatening cancers. Metastasis is the leading cause of cancer-related death in HCC. MiRNAs play essential roles in cancer metastasis. METHODS: Expression of miR-652-3p in HCC was assessed. Function experiments of miR-652-3p and trinucleotide repeat-containing gene 6A protein (TNRC6A) were performed both in vitro and in vivo. mRNA sequencing, PCR, and western blot were performed to verify the target genes and pathway of miR-652-3p. The lung metastasis and xenograft cancer model in nude mice was established to investigate the effects of the miR-652-3p and TRNC6A on tumor metastasis in vivo. The relationship between the expression of the miR-652-3p, TNRC6A and the prognosis of HCC patients was analyzed. RESULTS: Upregulated miR-652-3p was found in the tumor tissues of HCC, especially in metastatic HCC patients. Overexpression of miR-652-3p promoted and knockdown of miR-652-3p suppressed HCC metastasis both in vitro and in vivo. MiR-652-3p promoted HCC metastasis via regulating the EMT pathway. TNRC6A was identified as a direct target of miR-652-3p, and the knockdown of TNRC6A restored repressed EMT and HCC metastasis caused by the inhibition of miR-652-3p. Clinical results revealed that high expression of miR-652-3p and low expression of TNRC6A were positively correlated to shortened overall survival and disease-free survival in HCC patients. CONCLUSIONS: MiR-652-3p promotes EMT and HCC metastasis by inhibiting TNRC6A expression in HCC. MiR-652-3p and TNRC6A may serve as potential biomarkers to predict prognosis in HCC patients with metastasis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase NeoplásicaRESUMO
Hepatocellular carcinoma (HCC) is one of the most lethal tumor types worldwide. Glycosylation has shown promise in the study of tumor mechanisms and treatment. The glycosylation status of HCC and the underlying molecular mechanisms are still not fully elucidated. Using bioinformatic analysis we obtained a more comprehensive characterization of glycosylation of HCC. Our analysis presented that high glycosylation levels might correlate with tumor progression and poor prognosis. Subsequent Experiments identified key molecular mechanisms for ST6GALNAC4 promoting malignant progression by inducing abnormal glycosylation. We confirmed the contribution of ST6GALNAC4 to proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies revealed that ST6GALNAC4 may be induced abnormal TGFBR2 glycosylation, resulting in the higher protein levels of TGFBR2 and TGF[Formula: see text] pathway increased activation. Our study also provided a further understand of immunosuppressive function of ST6GALNAC4 through T antigen-galectin3+ TAMs axis. This study has provided one such possibility that galectin3 inhibitors might be an acceptable treatment choice for HCC patients with high T antigen expression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Sialiltransferases , Humanos , Antígenos Virais de Tumores , Carcinogênese , Carcinoma Hepatocelular/genética , Glicosilação , Neoplasias Hepáticas/genética , Receptor do Fator de Crescimento Transformador beta Tipo II , Sialiltransferases/genéticaRESUMO
As a traditional Chinese medicinal material, Lonicera japonica has a long medicinal history. The chemical constituents of Lonicera japonica are complex, mainly including iridoid glycosides, flavonoids, triterpenes, organic acids and volatile oil. Iridoid glycosides account for a higher proportion. In addition, modern pharmacological studies have shown that the iridoid glycosides have many pharmacological activities such as antivirus, anti-inflammation, anti-tumor, liver protection and lowering blood sugar. This review intends to systematically summarize the iridoid glycosides identified from Lonicera japonica and their pharmacological activities by searc-hing Chinese and English databases, in order to provide a reference for the further development and utilization of Lonicera japonica and for the improvement of quality standards of medicinal materials.
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Lonicera , Anti-Inflamatórios , Flavonoides , Glicosídeos/farmacologia , Glicosídeos Iridoides/farmacologia , Extratos VegetaisRESUMO
BACKGROUND: At present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of 99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis. METHODS: The animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH. 99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). RESULTS: At 2 weeks after the injection of hormone, 99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the 99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM. CONCLUSIONS: 99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.
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Anexinas , Necrose da Cabeça do Fêmur/diagnóstico , Necrose da Cabeça do Fêmur/etiologia , Imagem Molecular/métodos , Compostos de Organotecnécio , Esteroides/efeitos adversos , Animais , Meios de Contraste , Modelos Animais de Doenças , Suscetibilidade a Doenças , Necrose da Cabeça do Fêmur/metabolismo , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Coelhos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Aim: The occurrence of nonappendiceal cancer-specific death (non-ACSD) and its impact on overall survival are unclear. Methods: Patients were extracted from the Surveillance, Epidemiology, and End Results. Results: Nearly 33.2 and 24.0% patients suffered ACSD and non-ACSD. In a Cox proportional-hazards model, unmarried patients were at greater risk of mortality than were married patients. In a competing risk model, unmarried patients were at greater risk of non-ACSD than were married patients, but the risk of ACSD did not differ significantly according to marriage status. Conclusion: The overall survival of patients with appendiceal cancer was reduced by non-ACSD. A competing risk model was more predictive of the prognosis than was a Cox proportional hazards model.
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Neoplasias do Apêndice/mortalidade , Neoplasias/mortalidade , Adulto , Idoso , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/etiologia , Neoplasias do Apêndice/terapia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/terapia , Vigilância da População , Modelos de Riscos Proporcionais , Risco , Programa de SEER , Adulto JovemRESUMO
Mongolian folk medicine resource is the origin of Mongolian medicine development, even more important of which is the specialized Mongolian folk medicine resources with regional and high medicine quality, it processes distinctive national characteristics with irreplaceable important position in traditional Mongolian medicine. Nevertheless, due to the serious destroy of ecological environment and sharp increase of demands, etc. A lot of specialized Mongolian folk medicine resources were endangered, and there still existed some problems in the protection and exploitation and utilization. This paper intends to provide comprehensive insight into the species protection and exploitation and utilization states of specialized Mongolian folk medicine resources. The application and protection status and the existing problems were reviewed, and the development strategies of Mongolian folk medicine resource were analyzed.
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Conservação dos Recursos Naturais , Medicina Tradicional da Mongólia , Plantas Medicinais/crescimento & desenvolvimento , Conservação dos Recursos Naturais/métodos , Meio Ambiente , Mongólia , Plantas Medicinais/classificaçãoRESUMO
We present a theoretical model study of a quasi-three-level laser with particular attention given to the Tm:YAG laser. The oscillating conditions of this laser were theoretically analyzed from the point of the pump threshold while taking into account reabsorption loss. The laser oscillation at 2.02 µm with large stimulated emission sections was suppressed by selecting the appropriate coating for the cavity mirrors, then an efficient laser-diode side-pumped continuous-wave Tm:YAG crystal laser operating at 2.07 µm was realized. Experiments with the Tm:YAG laser confirmed the accuracy of the model, and the model was able to accurately predict that the high Stark sub-level within the H36 ground state manifold has a low laser threshold and long laser wavelength, which was achieved by decreasing the transmission of the output coupler.
Assuntos
Desenho Assistido por Computador , Lasers de Estado Sólido , Lasers , Modelos Teóricos , Refratometria/instrumentação , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de RadiaçãoRESUMO
BACKGROUND: Robotic-assisted surgery (RAS) is increasingly used for treating low rectal cancer. Its comparative effectiveness against laparoscopic surgery (LAS) in enhancing long-term anal function remains uncertain. METHODS: A meta-analysis was conducted to compare long-term anal function outcomes between patients undergoing RAS and LAS. Meta-regression and sensitivity analyses were performed to assess available evidence. Studies published up to September 2023 in English or Chinese were included. RESULTS: Seven studies were identified. RAS patients exhibited lower low anterior resection syndrome (LARS) scores (standardised mean difference [SMD] = -1.39; 95% confidence interval [CI]: -2.64 to -0.15) and Wexner scores (SMD = -0.74; 95% CI: -1.20 to -0.27) compared with LAS patients. However, RAS did not significantly reduce major LARS risk (odds ratio = 0.85; 95% CI: 0.68-1.04). CONCLUSIONS: RAS slightly improved postoperative anal function compared with LAS. Further studies with large samples are warranted to confirm or update our findings.
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Canal Anal , Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Retais/cirurgia , Laparoscopia/métodos , Canal Anal/cirurgia , Resultado do Tratamento , Seguimentos , Masculino , Complicações Pós-Operatórias , Feminino , Pessoa de Meia-IdadeRESUMO
Long non-coding RNAs (lncRNAs) play essential roles in a variety of biological processes. It has been recently reported that lncRNAs can regulate mRNA expression by binding to microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs). However, the involvement of this regulatory mechanism during cold acclimation in fish remains unclear. In this study, we constructed a ceRNA network mediated by lncRNAs in cold-acclimated zebrafish ZF4 cells through bioinformatic analysis of the mRNA, miRNA, and lncRNA profiles obtained from ZF4 cells cultured at 18 °C for 30 days. A previously uncharacterized lncRNA, MSTRG3207, was selected for further analysis. MSTRG3207 was upregulated and dre-miR-736 was downregulated during cold acclimation. MSTRG3207 was cloned by rapid amplification of cDNA ends (RACE) and functionally characterized. The binding of MSTRG3207 to dre-miR-736 was validated by dual-luciferase reporter assay. Under cold acclimation, MSTRG3207 promoted apoptosis by sponging dre-miR-736 and upregulating bbc3 and LOC101885512, two apoptotic genes targeted by dre-miR-736. Taken together, our findings indicate that MSTRG3207 upregulation promotes apoptosis by sponging dre-miR-736 during cold acclimation in fish.
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MicroRNAs , RNA Longo não Codificante , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , RNA Longo não Codificante/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , RNA Mensageiro/genética , Aclimatação/genéticaRESUMO
BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.
Assuntos
Biorretroalimentação Psicológica , Incontinência Fecal , Estudos Multicêntricos como Assunto , Nervo Pudendo , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais , Estimulação Elétrica Nervosa Transcutânea , Humanos , Biorretroalimentação Psicológica/métodos , Resultado do Tratamento , Estimulação Elétrica Nervosa Transcutânea/métodos , Incontinência Fecal/terapia , Incontinência Fecal/fisiopatologia , Incontinência Fecal/etiologia , Neoplasias Retais/cirurgia , Neoplasias Retais/terapia , Feminino , Pessoa de Meia-Idade , Síndrome , Masculino , Adulto , Diafragma da Pelve/fisiopatologia , Diafragma da Pelve/inervação , Recuperação de Função Fisiológica , China , Defecação , Idoso , Protectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Eletromiografia , ManometriaRESUMO
Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000 years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis, and novel treatment strategies are urgently needed. Mitochondria are key regulators of cellular homeostasis and potential targets for tumor therapy. Here, the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity is investigated and the potential therapeutic implications for HCC are assessed. TSPO is highly expressed in HCC and associated with poor prognosis. Gain- and loss-of-function experiments present that TSPO promotes HCC cell growth, migration, and invasion in vitro and in vivo. In addition, TSPO inhibits ferroptosis in HCC cells via enhancing the Nrf2-dependent antioxidant defense system. Mechanistically, TSPO directly interacts with P62 and interferes with autophagy, leading to the accumulation of P62. The P62 accumulation competes with KEAP1, preventing it from targeting Nrf2 for proteasomal degradation. Furthermore, TSPO promotes HCC immune escape by upregulating PD-L1 expression through Nrf2-mediated transcription. Notably, TSPO inhibitor PK11195 combines with anti-PD-1 antibody showing a synergistic anti-tumor effect in a mouse model. Overall, the results demonstrated that mitochondrial TSPO promotes HCC progression by inhibiting ferroptosis and antitumor immunity. Targeting TSPO can be a promising new strategy for HCC treatment.
Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte , Evasão da Resposta Imune , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Proteínas Mitocondriais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
OBJECTIVE: To evaluate the expressions and significances of CD147, OPN and MMP-2 in oral squamous cell carcinoma (OSCC). METHODS: The expressions of CD147, OPN and MMP-2 were detected by immunohistochemical method (SP) in 35 cases of ()SCC. The relationships between the expressions of CD147, OPN and MMP-2 and clinic histopathologic parameters of OSCC were analyzed. RESULTS: The expression rates of CD147, OPN and MMP-2 in OSCC tissues were 65.71%, 71.43% and 68.57% respectively. The expressions of CD147, OPN and MMP-2 were positively correlated with tumor histopathologic type, clinical stage and lymph node metastasis (P < 0.05), but not correlated with age, gender and the location of tumor (P > 0.05). The positive correlations were found among the expressions of CD147, OPN and MMP-2 (MMP-2 and CD147, r = 0. 653; MMP-2 and OPN, r = 0.540; CD147 and OPN, r = 0.381; P < 0.05). CONCLUSION: The expressions of CD147, OPN and MMP-2 increase in OSCC and may be the potential predictor of the malignant degree of OSCC.
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Basigina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Osteopontina/metabolismo , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de NeoplasiasRESUMO
Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota and metabolome after short-term (2 weeks) or long-term (20 weeks) IF and therefore clarify the potential mechanisms by which IF ameliorates DSS-induced colitis in a murine model. Thirty-two C57BL/6 male mice were equally divided into four groups and underwent IF intervention for 2 weeks (SIF group, n = 8), 20 weeks (LIF group, n = 8), or were allowed free access to food for 2 weeks (SAL group, n = 8) or 20 weeks (LAL group, n = 8). The thirty-two C57BL/6 male mice were accepted for the diet intervention of 2 weeks of IF or fed ad libitum. Colitis was induced by drinking 2% DSS for 7 days. Our findings showed that short-term IF prominently elevates the abundance of Bacteroides, Muibaculum and Akkermansia (p < 0.001, p < 0.001, p < 0.001, respectively), and decreased the abundance of Ruminiclostridium (p < 0.05). Long-term IF, however, decreased the abundance of Akkermansia and obviously increased the abundance of Lactobacillus (p < 0.05, p < 0.001, respectively). Metabolites mainly associated with nucleoside, carbohydrate, amino acid, bile acid, fatty acid, polyol, steroid and amine metabolism were identified in the faeces using untargeted GC/MS. In particular, inosine was extremely enriched after short-term IF and long-term IF (p < 0.01, p < 0.01, respectively); butyrate, 2-methyl butyric acid and valeric acid were significantly decreased after short-term IF (p < 0.001, p < 0.001, p < 0.01, respectively); and 2-methyl butyric acid was significantly increased after long-term IF (p < 0.001). The abundance of lithocholic acid (LCA), one of the secondary bile acids, increased significantly after short-term and long-term IF based on UPLC−MS/MS (p < 0.001, p < 0.5, respectively). Of note, IF markedly mitigated DSS-induced acute colitis symptoms and down-regulated pro-inflammatory cytokines IL-1α, IL-6, keratinocyte-derived chemokine (KC) and G-CSF levels in the serum (p < 0.01, p < 0.001, p < 0.05, p < 0.001, respectively). Furthermore, a correlation analysis indicated that the disease activity index (DAI) score and serum levels of IL-1α, IL-6, KC, and G-CSF were negatively correlated with the relative abundance of Akkermansia and the faecal metabolites LCA and inosine. This study confirmed that IF altered microbiota and reprogramed metabolism, which was a promising development in the attempt to prevent DSS-induced colitis. Moreover, our findings provide new insights regarding the correlations among the mucosal barrier dysfunction, metabolome, and microbiome.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Colite Ulcerativa/induzido quimicamente , Cromatografia Líquida , Modelos Animais de Doenças , Interleucina-6 , Jejum Intermitente , Espectrometria de Massas em Tandem , Colite/induzido quimicamente , Metaboloma , Akkermansia , Ácidos e Sais Biliares , Ácido Butírico , Sulfato de Dextrana , ColoRESUMO
Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC. SIGNIFICANCE: This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.
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Adenosina/análogos & derivados , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Circular/genética , Proteínas de Sinalização YAP/genética , Adenosina/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Metilação , Pessoa de Meia-Idade , Prognóstico , RNA Circular/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Sinalização YAP/metabolismoRESUMO
The function of the N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in hepatocellular carcinoma (HCC) has not been thoroughly investigated. Here we determined the clinical value, biological functions, and potential mechanisms of RBM15 in HCC. Expression of RBM15 was identified using tissue microarrays and online databases. A risk-prediction model based on RBM15 was developed and validated. We determined the biological role of RBM15 on HCC cells in vitro and in vivo. RNA sequencing was used to screen candidate targets of RBM15. Subsequently, the m6A dot blot assay, methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, RNA decay assay, and RNA immunoprecipitation qPCR were employed to explore the mechanisms of RBM15. Our study showed that RBM15 was highly expressed in HCC, and overexpression of RBM15 indicated a worse outcome. A new nomogram combining RBM15 with age and TNM stage was developed and validated to predict the outcome of HCC patients; our nomogram increased the prediction accuracy of the TNM system. Functionally, RBM15 facilitates the proliferation and invasiveness of HCC. RBM15-mediated m6A modification contributed to a post-transcriptional activation of YES proto-oncogene 1 (YES1) in an insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)-dependent manner. In addition, YES1 was confirmed as an oncogene in HCC cells by activating the mitogen-activated protein kinase (MAPK) pathway. In conclusion, RBM15-mediated m6A modification might facilitate the progression of HCC via the IGF2BP1-YES1-MAPK axis. RBM15 may be a promising biomarker in the outcome prediction of HCC.
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Objectives: The objective of this study was to provide a new classification method by analyzing the relationship between urine color (Ucol) distribution and urine dry chemical parameters based on image digital processing. Furthermore, this study aimed to assess the reliability of Ucol to evaluate the states of body hydration and health. Methods: A cross-sectional study among 525 college students, aged 17-23 years old, of which 59 were men and 466 were women, was conducted. Urine samples were obtained during physical examinations and 524 of them were considered valid, including 87 normal samples and 437 abnormal dry chemistry parameters samples. The urinalysis included both micro- and macro-levels, in which the CIE L*a*b* values and routine urine chemical examination were performed through digital imaging colorimetry and a urine chemical analyzer, respectively. Results: The results showed that L* (53.49 vs. 56.69) in the abnormal urine dry chemistry group was lower than the normal group, while b* (37.39 vs. 33.80) was greater. Urine color can be initially classified based on shade by grouping b*. Abnormal urine dry chemical parameter samples were distributed more in the dark-colored group. Urine dry chemical parameters were closely related to Ucol. Urine specific gravity (USG), protein, urobilinogen, bilirubin, occult blood, ketone body, pH, and the number of abnormal dry chemical parameters were all correlated with Ucol CIE L*a*b*; according to a stepwise regression analysis, it was determined that more than 50% of the variation in the three-color space values came from the urine dry chemical parameters, and the b* value was most affected by USG (standardized coefficient ß = 0.734, p < 0.05). Based on a receiver operating characteristic curve (ROC) analysis, Ucol ≥ 4 provided moderate sensitivity and good specificity (AUC = 0.892) for the detection of USG ≥ 1.020. Conclusions: Our findings on the Ucol analysis showed that grouping Ucol based on b* value is an objective, simple, and practical method. At the same time, the results suggested that digital imaging colorimetry for Ucol quantification is a potential method for evaluating body hydration and, potentially, health.
RESUMO
OBJECTIVE: The purpose of this study was to investigate the relationship between miR-152-3p and the KLF4/IFITM3 axis, thereby revealing the mechanism underlying colon cancer occurrence and development, consequently providing a promising target for colon cancer treatment. METHODS: Bioinformatics methods were implemented to analyze the differential expression of miRNAs and mRNAs in colon cancer, confirm the target miRNA, and predict the downstream targeted mRNAs. qRT-PCR and Western blot were performed to detect the expression of miR-152-3p, KLF4, and IFITM3. CCK-8 and colony formation assays were conducted for the assessment of cell proliferation, and flow cytometry was carried out for the detection of cell apoptosis. Finally, dual-luciferase reporter gene assay was employed to verify the targeting relationship between miR-152-3p and KLF4. RESULTS: miR-152-3p was highly expressed in colon cancer cells, whereas KLF4 was poorly expressed. Dual-luciferase assay verified that miR-152-3p targeted to bind to KLF4 and suppressed its expression. Moreover, silencing miR-152-3p or overexpressing KLF4 was found to downregulate IFITM3, thereby inhibiting cell proliferation and potentiating cell apoptosis. In rescue experiments, we found that miR-152-3p deficiency decreased the expression of IFITM3 and weakened cancer cell proliferation, and such effects were restored when miR-152-3p and KLF4 were silenced simultaneously. CONCLUSION: In sum, we discovered that miR-152-3p can affect the pathogenesis of colon cancer via the KLF4/IFITM3 axis.
Assuntos
Neoplasias do Colo/genética , Fatores de Transcrição Kruppel-Like/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Regiões 3' não Traduzidas , Apoptose/genética , Sítios de Ligação/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Biologia Computacional , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Neuroendocrine tumors (NETs) are a group of heterogeneous cancers arising from a variety of anatomic sites. Their incidence has increased in recent years. This study aimed to analyze the prognosis of NETs originating from different anatomic sites. METHODS: We identified 73,782 patients diagnosed with NETs from the Surveillance Epidemiology and Ends Results (SEER) database from 1973 to 2014. Clinical data were compared between patients with different primary tumor sites using the chi-squared test. Differences in survival among NET patients with different tumor sites were compared by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify the prognostic factors of overall survival. RESULTS: In this cohort, the lung/bronchus was the most common site of NETs, accounting for 30.6%, followed by the small intestine (22.2%), rectum (16.2%), colon (13.4%), pancreas (10.8%), and stomach (6.8%). Totally, 73,782 patients were selected for this cohort from 1973 to 2014. The median survival duration was 41 months. The 1-, 3-, 5-, and 10-year overall survival rates for patients with NETs were 72.8%, 52.7%, 39.4%, and 18.1%, respectively. Patients with NETs located in the rectum had the best prognosis, followed by those with NETs in the small intestine (HR, 1.660, 95% CI, 1.579, 1.744), lung/bronchus (HR, 1.786, 95% CI, 1.703, 1.874), stomach (HR, 1.865, 95% CI, 1.755, 1.982), and colon (HR, 1.896, 95% CI, 1.799, 1.999). Patients with NETs in the pancreas had the highest risk of mortality (HR, 2.034, 95% CI, 1.925, 2.148). CONCLUSION: Significant differences in survival were found among various primary tumor sites. NETs in the rectum had the best prognosis, while those in the pancreas had the worst. Primary tumor sites might be one of the most useful outcome predictors in patients with NETs.