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In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure-activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.
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BACKGROUND: Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis. METHODS: circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays. RESULTS: In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as "tumorigenic-angiogenic coupling". Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p. CONCLUSIONS: We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.
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Neoplasias Ósseas , Neoplasias Pulmonares , MicroRNAs , Osteossarcoma , Neoplasias Ósseas/patologia , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/patologia , RNA Circular/genéticaRESUMO
BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Large numbers of studies have focused on the long non-coding RNA (lncRNA) that plays essential roles in the progression of osteosarcoma. Nevertheless, the functions and underlying mechanisms of LncRNA NDRG1 in osteosarcoma remain unknown. METHODS: Differentially expressed lncRNAs between osteosarcoma and adjacent normal tissues were identified through RNA sequencing. The role of LncRNA NDRG1 in osteosarcoma proliferation and metastasis were investigated through in vitro and in vivo functional experiments. The interaction between LncRNA NDRG1 and miR-96-5p was verified through bioinformatic analysis and luciferase reporter assay. Regulation relationship between LncRNA NDRG1 and miR-96-5p was further evaluated by the rescue experiments. Additionally, the changes in the expression of epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were verified by Western blot. RESULTS: LncRNA NDRG1 was up-regulated in osteosarcoma cell lines and tissues and the expression of LncRNA NDRG1 was correlated with the overall survival of osteosarcoma patients. Functional experiments exhibited that LncRNA NDRG1 aggravated osteosarcoma proliferation and migration in vitro; meanwhile, animals experiments showed that LncRNA NDRG1 promoted osteosarcoma growth and metastasis in vivo. Mechanistically, LncRNA NDRG1 was found to aggravate osteosarcoma progression and regulate the PI3K/AKT pathway by sponging miR-96-5p. CONCLUSIONS: LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p. Therefore, LncRNA NDRG1 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Animais , Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante/genéticaRESUMO
We used UV-guided method to isolate and identify 12 secondary metabolites from Meehania fargesii var. Radicans for the first time, including eight triterpenoids (1-8), two phenylpropanoid derivatives (9-10) and two flavone glycosides (11-12). Their structures were identified by NMR spectroscopic methods, as well as literature comparison. The identified compounds and positive drugs (amoxicillin, omeprazole and clarithromycin) were further analyzed for their in silico docking interactions with HtrA using igemdock. Docking studies revealed the high binding affinity of phytochemicals at significant sites with HtrA, compounds 11 and 12 exhibiting stronger binding ability than standard drug, 1 and 3-10 demonstrating comparable docking capacity to standard drugs. The chemotaxonomic relationships were carried out to exploring the possibilities of other medicinal plants against Hp-induced gastric carcinoma. The results demonstrated there are closely chemotaxonomic similarity among several genera of the Lamiaceae family as well as among Lamiaceae, Actinidiaceae and Rosaceae families, indicating a similar chemical compositions and anti-Hp-induces gastric carcinoma activity among them.
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Carcinoma , Infecções por Helicobacter , Helicobacter pylori , Lamiaceae , Antibacterianos/farmacologia , Carcinoma/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologiaRESUMO
A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13â µM) and an excellent antioxidant activity (IC50 0.527±0.06â µM in ABTS assay, and 1.235±0.09â µM in DPPH assay, respectively), which was superior to vitaminâ C in ABTS (IC50 1.670±0.07â µM) and DPPH (IC50 19.10±0.40â µM) methods.
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Antineoplásicos , Delphinium , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Delphinium/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , SuccinatosRESUMO
Osteosarcoma (OS) is the most common bone malignant tumor. However, the genetic basis of OS pathogenesis is still not understood, and occurrence of chemo-resistance is a major reason for the high morbidity of OS patients. Recently, chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) has been identified as a gene related to malignant tumor progression. Unfortunately, its effects on OS development and drug resistance are still not understood. In the study, we attempted to investigate the effects of CHD1L on tumorigenesis and chemoresistance in OS. We found that CHD1L expression was markedly up-regulated in OS samples, especially in cisplatin (cDDP)-resistant patients. We also showed that OS cells with CHD1L knockdown were more sensitive to cDDP treatment with lower IC50 values. In addition, we found that CHD1L deletion markedly reduced cell proliferation and induced apoptosis in OS cells with cDDP resistance. Moreover, the properties of cancer stem cells were highly suppressed in cDDP-resistant OS cells following CHD1L knockdown. Furthermore, multidrug resistance protein 1 (MDR-1) expression levels were dramatically decreased in OS cells with cDDP resistance when CHD1L was suppressed. Functional analysis indicated that CHD1L knockdown clearly restrained the activation of ERK1/2, protein kinase B (AKT) and NF-κB signaling pathways in cDDP-resistant OS cells. Consistently, animal experiments suggested that CHD1L suppression mitigated cDDP resistance in the generated in vivo xenografts. Collectively, CHD1L could modulate chemoresistance of OS cells to cDDP, and thus may be inspiring findings for overcoming drug resistance in OS.
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Neoplasias Ósseas/tratamento farmacológico , Cisplatino/farmacologia , DNA Helicases/antagonistas & inibidores , Proteínas de Ligação a DNA/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Células-Tronco Neoplásicas/patologia , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND/OBJECTIVE: Brain metastasis in osteosarcoma (BMO) is rare and its clinical characteristics are often buried among studies on brain metastasis of bone and soft tissue sarcomas. The aim of the present study was to summarize the incidence, clinical characteristics, treatment and outcomes of patients with BMO. METHODS: This retrospective study included 7 patients with BMO who received treatment in our center between 2005 and 2019. The clinical medical records of the 7 patients, together with data of 70 BMO patients published in 33 articles and retrieved by means of PubMed and Medline, were analyzed, retrospectively. RESULTS: Data analysis of the 97 BMO patients showed a high correlation between the interval from the primary diagnosis to BMO occurrence and the interval from the primary diagnosis to prior metastases. Multivariate analysis showed that chemotherapy, radiotherapy and surgery were three main factors affecting the overall survival of BMO patients (HR = 0.427; HR = 0.372; HR = 0.296). Surgery combined with chemotherapy or radiotherapy offered a better overall survival than surgery alone. CONCLUSION: Patients with BMO may obtain survival benefits from regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy. SYNOPSIS: This is a retrospective study describing the characteristics of metastasic intervals, locations, clinical features and prognosis in 97 patients with brain metastasis of osteosarcoma (BMO). Multivariate analysis showed that chemotherapy was effective as surgery and radiotherapy for the treatment of BMO. Our findings emphasize the importance of regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy.
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BACKGROUND/AIMS: This study focused on the oncogenic role of Diphthamide biosynthesis 1 (DPH1) in colorectal cancer (CRC) cells. METHODS: The expression of DPH1 was determined by quantitative RT-PCR analysis and western blotting in CRC tissues. The role of DPH1 in CRC cells was investigated via cell viability and invasion assays under the condition of DPH1 silencing or overexpression. Bioinformatics analysis and luciferase reporter analysis were used to identify the upstream microRNA which might regulate DPH1.The inverse correlation between the microRNA and DPH1 was also detected in CRC cells. RESULTS: We identified an unexpected role for DPH1 as an oncogene in CRC cells. The tumour-suppressive miR-218-5p regulates DPH1 directly and negatively. Loss of miR-218-5p drives the oncogenic role of DPH1 in CRC cells. CONCLUSION: The modulation of DPH1 by miR-218-5p may be an important regulatory axis during CRCtumourigenesis.
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Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Regiões 3' não Traduzidas , Adenocarcinoma/metabolismo , Idoso , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Neoplasias Colorretais/metabolismo , Feminino , Células HT29 , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genéticaRESUMO
Emerging evidence has suggested that circulating microRNAs (miRNAs) in serum/plasma can serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in osteosarcoma, a primary malignant bone tumor with high morbidity in young adults and adolescents. The objective of this study was to investigate whether circulating miRNAs in serum could be a useful biomarker for detecting osteosarcoma and monitoring tumor dynamics. Serum samples were obtained from 60 patients before surgery, 28 patients after 1 month of surgery, and 60 healthy individuals. The study was divided into three steps: (1) initial screening of the profiles of circulating miRNAs in pooled serum samples from both healthy controls and pre- and postoperative osteosarcoma patients using a TaqMan low-density qPCR array (TLDA); (2) evaluation of miRNA concentration in individual serum samples from 60 preoperative osteosarcoma patients and 60 healthy controls by a quantitative RT-PCR assay; and (3) evaluation of miRNA concentration in paired serum samples from 28 pre- and postoperative osteosarcoma patients by a quantitative RT-PCR assay. The initial analysis showed that concentrations of serum miRNAs were significantly altered between preoperative osteosarcoma patients and healthy controls and between pre- and postoperative osteosarcoma patients. The quantitative RT-PCR assay showed that serum miR-199a-5p concentrations were significantly higher in osteosarcoma patients than in controls. The value of the area under the ROC curve was 0.8606. Serum levels of miR-199a-5p were significantly lower in post- than preoperative samples. The results indicated the potential of circulating miRNAs as novel noninvasive biomarkers for detecting and monitoring osteosarcoma.
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Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Osteossarcoma/sangue , Adolescente , Adulto , Neoplasias Ósseas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Osteossarcoma/genética , Osteossarcoma/patologia , PrognósticoRESUMO
BACKGROUND: Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown. METHODS: In this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cells in vitro were assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT. RESULTS: We identified a specific target site for miR-16 in the 3'-untranslated region (3'-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells. CONCLUSIONS: Our findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation.
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Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Metiltransferases/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Apoptose , Neoplasias da Mama/genética , Carcinoma Hepatocelular/genética , Biologia Computacional , Humanos , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Células MCF-7 , Metiltransferases/genética , MicroRNAs/genética , RNA Interferente Pequeno , Regulação para CimaRESUMO
Ampelopsin (AMP), a novel flavonoid, has been shown to effectively inhibit the proliferation and induce apoptosis of some prostate cancer and breast cancer cell lines. Whether AMP has chemopreventive effects on the cell growth and apoptosis of human osteosarcoma MG-63 cells remains unknown. In the present study, MG-63 cells were exposed to different concentrations (0, 25, 50, 75, 100 µmol/L) of AMP for 24, 48, 72 and 96 h and then the cell viability was measured by CCK-8 assay. The AMP-induced apoptotic cells were identified by Hochest33258 staining and quantified by Annexin V-FITC/PI double staining using flowcytometry (FCM). The effect of ampelopsin (AMP) on cell cycle was evaluated using PI staining with FCM. The protein levels of cyclin A, CDK2 and p21(CIP1) were measured by Western blotting. The cell viability was reduced in a time- and dose-dependent manner after exposure to AMP atarangeof 20-100 µmol/L. For the treatment of AMP, increases of apoptotic index and rate were observed in MG-63 cells. The AMP blocked cells in the G0/G1 phase of the cell cycle. Furthermore, AMP increased p21(CIP1) expression but decreased cyclin A and CDK2 expression after AMP exposure. AMP inhibited cell growth and induced apoptosis and G0/G1 phase arrest in MG-63 cells in vitro, with the potential mechanism of the negative regulation of cell cycle-related protein.
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Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Fase de Repouso do Ciclo Celular/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the erectile and ejaculatory function of sacral tumor patients after sacral nerve root resection and investigate the relationship of erectile and ejaculatory dysfunction (EED) with the level of sacral nerve injury. METHODS: This retrospective study included 47 male patients aged 16 to 63 (32.6 +/- 6.8) years treated by sacral tumor resection between January 2008 and August 2013. According to the levels of the sacral nerve roots spared in surgery, the patients were divided into four groups: bilateral S1-S3 (n=16), unilateral S1-S3 (n=21), unilateral S1-S2 (n=6), and unilateral S1 (n=4). The patients were followed up for 12 to 41 (27.2 +/- 10.9) months by questionnaire investigation, clinic review, and telephone calls about their erectile and ejaculatory function at 3, 6 and 12 months after surgery and in August 2013. RESULTS: In the bilateral S1-S3 group, the incidence rates of EED were 31.25% (5/16), 25% (4/16), and 12.5% (2/16) at 3, 6, and 12 months respectively after surgery, with recovery of erectile and ejaculatory function in August 2013. The incidence rates of EED in the unilateral S1-S3 group were 85.71% (18/21), 71.43% (15/21), 52.38% (11/21), and 42.86% (9/21) at 3, 6 and 12 months and in August 2013, respectively; those in the unilateral S1-S2 group were 100% (6/6), 83.33% (5/6), 83.33% (5/6), and 66.67% (4/6) at the four time points; and those in the unilateral S1 group were all 100% (4/4). No statistically significant differences were found in the incidence rate of EED among the patients of different ages or tumor types (P > 0.05). CONCLUSION: The incidence of postoperative EED in male patients treated by sacral tumor resection is closely related to the mode of operation. Sparing the S3 nerve root at least unilaterally in sacral tumor resection is essential for protecting the erectile and ejaculatory function of the patient.
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Ejaculação/fisiologia , Disfunção Erétil/etiologia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Raízes Nervosas Espinhais/cirurgia , Adolescente , Adulto , Disfunção Erétil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Estudos Retrospectivos , Sacro , Raízes Nervosas Espinhais/lesões , Inquéritos e Questionários , Adulto JovemRESUMO
Combining iron-carbon micro-electrolysis and autotrophic denitrification is promising for nitrate removal from wastewater. In this study, four continuous reactors were constructed using CO2 and weak magnetic field (WMF) to address challenges like iron passivation and pH stability. In the reactors with CO2 + WMF (10 and 35 mT), the increase in total nitrogen removal efficiency was significantly higher (96.2 ± 1.6 % and 94.1 ± 2.7 %, respectively) than that of the control (51.6 ± 2.7 %), and Fe3O4 converted to low-density FeO(OH) and FeCO3, preventing passivation film formation. The WMF application decreased the N2O emissions flux by 8.7 % and 20.5 %, respectively. With CO2 + WMF, the relative enzyme activity and abundance of denitrifying bacteria, especially unclassified_Rhodocyclaceae and Denitratisoma, increased. Thus, this study demonstrates that CO2 and WMF optimize the nitrate removal process, significantly enhancing removal efficiency, reducing greenhouse gas emissions, and improving process stability.
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Processos Autotróficos , Dióxido de Carbono , Carbono , Desnitrificação , Ferro , Campos Magnéticos , Nitratos , Dióxido de Carbono/metabolismo , Ferro/química , Nitratos/metabolismo , Eletrólise , Nitrogênio , Reatores Biológicos , Bactérias/metabolismo , Purificação da Água/métodos , Águas Residuárias/químicaRESUMO
With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.
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Insuficiência Adrenal , Humanos , Feminino , Idoso , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/etiologia , Insuficiência Adrenal/diagnóstico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Doença de Addison/tratamento farmacológico , Doença de Addison/diagnóstico , Doença de Addison/induzido quimicamente , Doença de Addison/etiologia , Hidrocortisona/uso terapêuticoRESUMO
With the widespread vaccination of COVID-19 vaccine, a few cases have been reported that COVID-19 vaccine may cause endocrine disorders. A 59-y-old man presented with a loss of appetite after the first COVID-19 vaccination, which resolved spontaneously after 3 d. After the second COVID-19 vaccination, the symptoms including the loss of appetite, nausea, and vomiting reappeared and worsened along with loss of vision. He was found to have severe hyponatremia, and further investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and Rathke's cleft cyst. The patient responded well to glucocorticoid and levothyroxine supplementation, and at 1-y follow-up the patient developed hypogonadism. We hypothesize that hypophysitis is probably induced by COVID-19 vaccine and report the rare but serious adverse reactions for early recognition and intervention.
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Vacinas contra COVID-19 , COVID-19 , Cistos do Sistema Nervoso Central , Hipofisite , Humanos , Masculino , Cistos do Sistema Nervoso Central/complicações , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hipofisite/induzido quimicamente , Pessoa de Meia-IdadeRESUMO
Circular RNAs (circRNAs) are a class of non-coding RNAs which take part in the regulation of the initiation and development of different types of cancer. Numerous studies have demonstrated that circRNAs are involved in the progression of osteosarcoma (OS) as well. Thus, we put our emphasis on the exploration of crucial circRNAs in the process of OS initiation and progression. Using RNA sequencing, we found that circSATB2 was highly expressed in OS tissues compared with adjacent normal tissues. Then, we confirmed the high expression of circSATB2 in OS cell lines and OS tissues and its high expression was related to poor prognosis of OS patients. Functional experiments exhibited that circSATB2 promoted OS proliferation and migration in vitro, primary OS model and OS lung metastasis model showed that circSATB2 aggravated OS progression in vivo. Mechanistically, circSATB2 was found to promote OS progression through sponging miR-661 and FUS regulating the mRNA of ZNFX1. Therefore, circSATB2 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Circular , Humanos , Antígenos de Neoplasias , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Circular/genética , RNA Mensageiro/genética , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismoRESUMO
FRS2 has demonstrated oncogenic roles in various malignancies, including liposarcoma and giant cell tumor of bone. However, its role in osteosarcoma remains less understood, and the upstream regulatory molecules influencing FRS2 remain unclear. This study aims to explore the clinical implications and biological function of FRS2 in osteosarcoma, and the potential regulatory microRNAs (miRNAs) governing its expression. Our study indicated significant upregulation of FRS2 in osteosarcoma cells and tissues by Western blotting and immunohistochemical staining. Elevated FRS2 expression correlated positively with increased angiogenesis and poor prognosis, possibly serving as an independent prognostic indicator for osteosarcoma patients. Functional assays revealed that attenuating FRS2 in osteosarcoma cells could mitigate proliferation, migration, and angiogenesis of vascular endothelial cells. Further investigations revealed that miR-429 and miR-206 directly targeted FRS2, exerting a negative regulation on its expression. Furthermore, FRS2 played a role in repressing osteosarcoma advancement influenced by miR-429 or miR-206. In summary, FRS2, influenced by miR-429 and miR-206, emerges as a promising therapeutic candidate for antiangiogenic osteosarcoma treatments.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Células Endoteliais/metabolismo , Angiogênese , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Neoplasias Ósseas/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genéticaRESUMO
Objective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference. Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA. Results: The OWSA-REI (26.5±18.5 events/h) correlated well with PSG-AHI (33.2±25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: -6.7, 95% CI:16.0 to -29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values. Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for smartwatches to become a complementary tool to PSG, which is particularly useful for larger-scale preliminary screenings.
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The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan-Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two-phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14-miRNA profile differed between tumor and NAT samples. Downregulation of miR-29c-3p and miR-219-5p were found to be associated with advanced clinical stages of meningioma. Kaplan-Meier analysis showed that high expression of miR-190a and low expression of miR-29c-3p and miR-219-5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR-190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes.