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BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. METHODS: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.
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Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Acetiltransferase N-Terminal E , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animais , Camundongos , Acetiltransferase N-Terminal E/metabolismo , Acetiltransferase N-Terminal E/genética , Masculino , Feminino , Progressão da Doença , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Pessoa de Meia-Idade , Acetiltransferases N-TerminalRESUMO
Drug resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a primary factor affecting their therapeutic efficacy in human non-small cell lung cancer (NSCLC). NSCLC cells can undergo epithelial-mesenchymal transition (EMT) induced by many factors in the tumour microenvironment (TME), which plays a crucial role in tumour drug resistance. In this study, a multicellular lung-on-a-chip that can realise the cell co-culture of the human non-small cell lung cancer cell line HCC827, human foetal lung fibroblasts (HFL-1), and human umbilical vein endothelial cells (HUVECs) is prepared. The TME was simulated on the chip combined with perfusion and other factors, and the drug evaluation of osimertinib was performed to explore the drug resistance mechanism of EGFR-TKIs. In the early stages, a two-dimensional static cell co-culture was achieved by microchip, and the results showed that HFL-1 cells could be transformed into cancer-associated fibroblasts (CAFs), and HCC827 cells could undergo EMT, both of which were mediated by Interleukin-6 (IL-6). Vimentin (VIM) and Alpha Skeletal Muscle Actin (a-SMA) expression of HFL-1 was upregulated, whereas E-cadherin (E-cad) expression of HCC827 was down-regulated. Further, N-cadherin (N-cad) expression of HCC827 was upregulated. In both the static cell co-culture and multicellular lung-on-a-chip, HCC827 cells with CAFs co-culture or IL-6 treatment developed resistance to osimertinib. Further use of the IL-6 antibody inhibitor tocilizumab could reverse EGFR-TKI resistance to a certain extent. Combination therapy with tocilizumab and EGFR-TKIs may provide a novel therapeutic strategy for overcoming EGFR-TKI resistance caused by EMT in NSCLC. Furthermore, the lung-on-a-chip can simulate complex TME and can be used for evaluating tumour resistance and exploring mechanisms, with the potential to become an important tool for personalised diagnosis, treatment, and biomedical research.
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Acrilamidas , Compostos de Anilina , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Receptores ErbB , Células Endoteliais da Veia Umbilical Humana , Dispositivos Lab-On-A-Chip , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Indóis , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas , Microambiente Tumoral/efeitos dos fármacosRESUMO
Dystrophic epidermolysis bullosa (DEB) is a rare disease and the associated esophageal stricture is frequently complicated by the lack of clinical experience. The present study reported a very rare case of DEB in a 37-year-old male, who was admitted to Shenzhen Hospital (Shenzhen, China) due to an esophageal stricture. The patient received esophageal dilation under digital subtraction angiography. In this patient, dilation therapy was effective and safe. The patient underwent skin biopsies, and histological examination of the resected tissue specimens confirmed DEB diagnosis. The patient was followed up in the Department of Thoracic Surgery, Shenzhen Hospital, for 2 years without any recurrence of esophageal stricture. This is the first case report of dilation therapy in a very rare case of DEB with a satisfactory outcome, but the long-term efficacy needs further observation. In addition, the latest relevant literature was reviewed and it was found that this treatment is uncommonly reported, as is the condition.
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The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.
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Metabolismo dos Lipídeos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Proteínas de Ligação a RNA , Neoplasias do Colo do Útero , Feminino , Humanos , Ácidos Graxos , Lipogênese , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Metástase Linfática , Neoplasias do Colo do Útero/genética , Proteínas de Ligação a RNA/genéticaRESUMO
Lung cancer has become the primary cause of cancer-related deaths because of its high recurrence rate, ability to metastasise easily, and propensity to develop drug resistance. The wide-ranging heterogeneity of lung cancer subtypes increases the complexity of developing effective therapeutic interventions. Therefore, personalised diagnostic and treatment strategies are required to guide clinical practice. The advent of innovative three-dimensional (3D) culture systems such as organoid and organ-on-a-chip models provides opportunities to address these challenges and revolutionise lung cancer research and drug evaluation. In this review, we introduce the advancements in lung-related 3D culture systems, with a particular focus on lung organoids and lung-on-a-chip, and their latest contributions to lung cancer research and drug evaluation. These developments include various aspects, from authentic simulations and mechanistic enquiries into lung cancer to assessing chemotherapeutic agents and targeted therapeutic interventions. The new 3D culture system can mimic the pathological and physiological microenvironment of the lung, enabling it to supplement or replace existing two-dimensional culture models and animal experimental models and realize the potential for personalised lung cancer treatment.
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Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. The research strived to establish a prognostic model based on malignancy-related risk score (MRRS) in LUAD. Methods: We applied the single-cell RNA sequencing (scRNA-seq) data from Tumor Immune Single Cell Hub database to recognize malignancy-related geneset. Meanwhile, we extracted RNA-seq data from The Cancer Genome Atlas database. The GSE68465 and GSE72094 datasets from the Gene Expression Omnibus database were downloaded to validate the prognostic signature. Random survival forest analysis screened MRRS with prognostic significance. Multivariate Cox analysis was leveraged to establish the MRRS. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the malignancy-related signature. In addition, we used qRT-PCR to explore the expression profile of MRRS-constructed genes in LUAD cells. Results: The scRNA-seq analysis revealed the markers genes of malignant celltype. The MRRS composed of 7 malignancy-related genes was constructed for each patient, which was shown to be an independent prognostic factor. The results of the GSE68465 and GSE72094 datasets validated MRRS's prognostic value. Further analysis demonstrated that MRRS was involved in oncogenic pathways, genetic mutations, and immune functions. Moreover, the results of qRT-PCR were consistent with bioinformatics analysis. Conclusion: Our research recognized a novel malignancy-related signature for predicting the prognosis of LUAD patients and highlighted a promising prognostic and treatment marker for LUAD patients.
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Viral infectious diseases remain a global public health problem. The rapid and widespread spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has had a severe impact on the global economy and human activities, highlighting the vulnerability of humans to viral infectious diseases and the urgent need to develop new technologies and effective treatments. Organ-on-a-chip is an emerging technology for constructing the physiological and pathological microenvironment of human organs in vitro and has the advantages of portability, high throughput, low cost, and accurate simulation of the in vivo microenvironment. Indeed, organ-on-a-chip provides a low-cost alternative for investigating human organ physiology, organ diseases, toxicology, and drug efficacy. The lung is a main target organ of viral infection, and lung pathophysiology must be assessed after viral infection and treatment with antiviral drugs. This review introduces the construction of lung-on-a-chip and its related pathophysiological models, focusing on the in vitro simulation of viral infection and evaluation of antiviral drugs, providing a developmental direction for research and treatment of viral diseases.
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COVID-19 , Viroses , Humanos , SARS-CoV-2 , Avaliação de Medicamentos , Antivirais/farmacologia , Antivirais/uso terapêutico , Viroses/tratamento farmacológico , PulmãoRESUMO
We report a female patient, who presented as a carcinoma of unknown primary site with multiple tumors in breast, lung, stomach, and ovary, was confirmed to be lung adenocarcinoma as primary cancer through detecting EML4-ALK rearrangement by the next generation sequencing (NGS). The patient was treated with crizotinib and resulted in significant regression of the primary and metastatic tumors, but resistance to crizotinib was developed 5 months after the treatment. Targeted therapy was, therefore, switched to alectinib, one of the second-generation of anaplastic lymphoma kinase (ALK) inhibitors, with excellent therapeutic response till November 16th, 2021. This study suggested that NGS be recommended to detect ALK rearrangement in the patients with carcinoma of unknown primary site, and that resistance to targeted therapy with ALK inhibitors should be considered for personalized precision medicine.
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BACKGROUND: The prevalence of ectopic thyroid tissue is 1 in every 100,000 to 300,000 persons in the general population, and ectopic thyroid tissue in the bilateral lung lobes is even rarer. Due to its rarity, there is no definitive or standard guidance on the diagnosis and treatment of ectopic thyroid tissue presenting as multiple bilateral pulmonary nodules. CASE PRESENTATION: A 56-year-old woman presented with multiple bilateral pulmonary nodules, and the patient had a history of hyperthyroidism but had no symptoms of ectopic thyroid tissue. Computed tomography (CT) demonstrated multiple solid nodules in both lungs, and the largest nodule (sized 15 × 14 mm) was located in segment 5 of the upper left lung. The initial diagnosis based on imaging was metastatic malignancies. Positron emission tomography-computed tomography (PET-CT) showed multiple bilateral intrapulmonary nodules that had slightly increased metabolism (SUVmax 1.7). The largest pulmonary nodule and another nodule in the left lung were resected by video-assisted thoracoscopy surgery (VATS). The pathological and immunohistochemical (IHC) examinations confirmed a diagnosis of ectopic thyroid tissue. No postoperative adjuvant therapy was given, and the patient was discharged 3 days after the operation and had regular follow-up examinations. CONCLUSION: The diagnosis of ectopic thyroid tissue in the bilateral lung lobes is extremely difficult and should be considered carefully. PET-CT and surgical resection of intrapulmonary nodules are alternatives for clinicians in diagnosing ectopic thyroid tissue. Regular postoperative follow-up is needed.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Disgenesia da Tireoide , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Cirurgia Torácica Vídeoassistida/métodos , Disgenesia da Tireoide/diagnóstico , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. METHODS: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. RESULTS: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341-3.405) and the 11-20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359-3.143). CONCLUSIONS: The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline.
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COVID-19/psicologia , Dieta/normas , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Comportamento de Redução do Risco , Adulto , COVID-19/prevenção & controle , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression in vivo. miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression in vivo. In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression.
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BACKGROUND: Vascular air embolism (VAE) is a rare but important complication that has not been paid enough attention to in the medical process such as surgery and anesthesia. CASE PRESENTATION: We report for the first time that a 54-year-old male patient with central lung cancer developed severe complications of CAE after right pneumonectomy. After targeted first-aid measures such as assisted breathing, mannitol dehydration and antibiotic treatment, the patient gradually improved. The patient became conscious at discharge after 25 days of treatment but left limb was left with nerve injury symptoms. CONCLUSION: We analyzed the possible causes of CAE in this case, and the findings from this report would be highly useful as a reference to clinicians.
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Carcinoma de Células Escamosas/cirurgia , Infarto Cerebral/diagnóstico por imagem , Embolia Aérea/diagnóstico , Embolia Intracraniana/diagnóstico , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/diagnóstico , Angiografia Cerebral , Infarto Cerebral/etiologia , Infarto Cerebral/terapia , Angiografia por Tomografia Computadorizada , Diuréticos Osmóticos/uso terapêutico , Embolia Aérea/complicações , Embolia Aérea/fisiopatologia , Embolia Aérea/terapia , Humanos , Embolia Intracraniana/complicações , Embolia Intracraniana/fisiopatologia , Embolia Intracraniana/terapia , Masculino , Manitol/uso terapêutico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Respiração ArtificialRESUMO
Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.
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BACKGROUND: Severe flail chest is a life-threatening situation. The Nuss procedure is a new effective treatment for severe flail chest patients who cannot be weaned from prolonged mechanical ventilation in the last few years. However, the procedure is not suitable when there are multiple fractures in both the anterior and lateral chest walls. Here, we reported a rare case of severe flail chest in a patient who suffered multiple fractures in both the anterior and lateral chest walls in a traffic accident. CASE PRESENTATION: A 49-year-old patient suffered severe flail chest by a steering wheel in a traffic accident with multiple fractures in both the anterior and lateral chest walls. In the beginning, the patient was administrated with mechanical ventilation because of acute respiratory distress syndrome (ARDS) for more than 1 week. Then the patient suffered from a severe lung infection and decreased blood oxygen saturation. After a multidiscipline discussion (MDT), three rib fixation plates were first used to rebuild the stability of lateral chest walls, then two Nuss bars were inserted to eliminate paradoxical movement in the anterior chest wall. Finally, the patient recovered smoothly after the combining procedure. CONCLUSIONS: Severe flail chest patients with both the anterior and lateral chest walls after trauma are in a life-threatening situation, and require an appropriate procedure to get out of danger in time. Rib fixation is an effective treatment when the fractured sites are few and the fractured area is small. The Nuss procedure is a new effective method for severe flail chest with multiple fractures in an anterior chest wall, which is also a minimally invasive and short time-consuming procedure. However, it does not suitable for the patient with multiple fractures in lateral chest walls. Combining the use of Nuss procedure and rib fixation can solve severe flail chest with multiple ribs and sternum fractures in both the anterior and lateral chest walls, and the outcome of this procedure is satisfying in the present rare case.
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Tórax Fundido/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas das Costelas/complicações , Acidentes de Trânsito , Humanos , Masculino , Pessoa de Meia-Idade , Costelas/lesões , Esterno/lesões , Resultado do TratamentoRESUMO
Low selectivity is a major problem for cancer theranostics that has promoted the development of molecularly-responsive nanomaterials. Herein, we report a novel doxorubicin (DOX)-loaded degradable cobalt oxide nanoprism (Co3O4-DOX) for T1/T2 ratiometric magnetic resonance imaging (MRI)-monitored synergistic cancer therapy that simultaneously responds to intratumoral oxidability and acidity. Co3O4-DOX degraded under both H2O2-rich and acidic conditions, producing Co3+ and releasing DOX, not only resulted in an MRI contrast switch from T2 to T1, but also led to DOX luminescence recovery by weakening energy transfer. Thus, highly sensitive and selective H2O2 detection was achieved by these changes in MRI and luminescence signals. Importantly, Co3O4-DOX showed outstanding T1/T2 ratiometric MRI performance in vivo, significantly improving the contrast between tumor and normal tissues. Moreover, the produced Co3+ also resulted in intracellular radical generation for chemodynamic therapy, which had a synergistic effect with the photothermal and chemotherapy induced by Co3O4 and DOX, respectively. Under ratiometric MRI guidance, successful synergistic cancer therapy was performed on a tumor-bearing mice model. This work provides a new imaging application to improve selectivity that uses molecularly-responsive magnetic nanomaterials for ratiometric MRI tumor imaging and cancer theranostics.
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Imageamento por Ressonância Magnética/métodos , Nanoestruturas/química , Animais , Cobalto/química , Meios de Contraste/química , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Peróxido de Hidrogênio , Camundongos , Neoplasias/tratamento farmacológico , Oxirredução , Óxidos/química , Fototerapia , Nanomedicina Teranóstica/métodosRESUMO
Oxidative stress, as an essential cause to many diseases via irreversible biomolecule oxidation, can be induced by casual-contacted nanomaterials, which can generate hydroxyl radical (â¢OH) due to their active surface capacity. Herein, we report a novel upconversion nanoprobe for ratiometric â¢OH detection and monitoring titanium oxide nanomaterial-induced oxidative stress. Unlike previously developed nanoprobes, the â¢OH-responsive acceptor in these nanoprobes can be rapidly prepared and easily recycled. With a detection limit of â¼2 nM and a broad linear range of 4 nM-16 µM, the nanoprobe is suitable for both in vitro and in vivo applications. The facile preparation and recyclable strategy provide a new method for developing novel nanoprobes that can directly detect hazardous molecules in biological samples and systems.
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Corantes Fluorescentes/química , Hepatócitos/efeitos dos fármacos , Radical Hidroxila/análise , Nanopartículas/química , Estresse Oxidativo , Titânio/farmacologia , Animais , Linhagem Celular , Hepatócitos/química , Humanos , Injeções Intravenosas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Propriedades de Superfície , Titânio/administração & dosagem , Titânio/químicaRESUMO
To achieve accurate tumor location and highly efficient cancer therapy effect, the properties of cancer theranostic agents should be optimized and enhanced. In this work, ultra-small Nd doped NaDyF4 were firstly reported as novel contrast agents for near-infrared second window downconversion luminescence (NIR II DCL) and magnetic resonance imaging. Based on the optimization strategy, gallic acid-Fe(III) complex modified NaDyF4:10%Nd (NaDyF4:10%Nd-GA-Fe) was selected as the optimal agent with high transversal relaxivity, strong NIR II DCL, high photothermal conversion efficiency, and low toxicity. In vitro experiment found that it can be aggregated rapidly in low pH condition, leading to the particle size increasing. Due to the theranostic properties coupled in NaDyF4:10%Nd-GA-Fe are size dependent, properties enhancement was observed within the pH responsive aggregation progress. Further study in small animal model bearing tumor demonstrated the enhanced cancer theranostic by in situ aggregation. The optimized nanoagents have potential applications in medical and also provide a novel strategy for future study of cancer theranostic enhancement.
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Imageamento por Ressonância Magnética/métodos , Neodímio/química , Nanomedicina Teranóstica/métodos , Modelos Teóricos , FototerapiaRESUMO
The aim of the study was to compare the efficacy and safety between high-intensity focused ultrasound (HIFU) treatment and uterine artery embolization (UAE) treatment; we retrospectively analyzed 152 cases with cesarean scar pregnancy (CSP). Based on our inclusion and exclusion criteria, 152 patients (average age, 31.8â±â4.6 years old) with CSP were eligible for the HIFU group (85 patients) or the UAE group (77 patients). All patients in 2 groups received the treatment with suction curettage under hysteroscopy prior to HIFU or UAE treatment and followed up for 12 months. The assessment criteria of treatment efficacy included the success rate, intraoperative blood loss, duration of vaginal bleeding, normal menstrual function recovery time, time for ß-human chorionic gonadotrophin (ß-HCG) back to normal level, duration of hospital stays, and other adverse effects. Following up for 12 months, the HIFU group was of less intraoperative blood loss (76.38â±â22.89 vs 114.42â±â30.34âmL, Pâ=â.02), shorter duration of postoperative vaginal bleeding (11.28â±â3.65 vs 15.77â±â7.24 days, Pâ=â.01) and lower adverse effects rate comparing to the UAE group. However, the HIFU group have longer time for the ß-HCG recovery to the normal level (35.28â±â9.86 vs 29.91â±â7.29, Pâ=â.03). Additionally, there were no significantly statistic differences between the 2 groups in baseline characteristics, success rate, and average time of gestational sac disappeared and menstrual recovery and hospital stay. Thus, we concluded that the method of both HIFU and UAE combined with suction curettage under hysteroscopy is safe and effective in the management of CSP. Meanwhile, HIFU is a better therapy option than UAE for those women who are seeking complete relieve of symptom to gain fertility.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Gravidez Ectópica/terapia , Embolização da Artéria Uterina , Adulto , Perda Sanguínea Cirúrgica , Cesárea/efeitos adversos , Gonadotropina Coriônica Humana Subunidade beta/sangue , Cicatriz/etiologia , Feminino , Seguimentos , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Humanos , Histeroscopia , Hemorragia Pós-Operatória , Gravidez , Gravidez Ectópica/sangue , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Embolização da Artéria Uterina/efeitos adversos , Hemorragia Uterina , Curetagem a VácuoRESUMO
Hydroxyl radical (â¢OH) is an important marker of the progress of heavy metal induced oxidative stress. However, most reported probes and detection methods cannot meet the need of monitoring the â¢OH concentration within the whole progress because of the limited linear range. Besides, a low detection limit, high sensitivity, and good selectivity were also required. In this study, an ultrahigh sensitivity multifunctional nanoprobe (ICG-modified NaLuF4:Yb,Er) was developed to evaluate heavy metal induced oxidative stress by detecting â¢OH concentration, with a colorimetric, upconversion luminescence, and photothermal stepped method. This method has a broad linear detection range, from 16 pM to 2 µM, and a low detection limit of 4 pM. Besides, the nanoprobe showed less response to ions, amino acids, biomolecules, and other radical oxygen species (H2O2 and O2-) than â¢OH. This highly selective, highly sensitive probe with a broad linear detection range has great potential utility for monitoring â¢OH concentration in live hypatocyte within the progress of heavy metal induced oxidative stress, with probable in vivo applications in the future.