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MicroRNA is regarded as a significant biomarker for cancer diagnosis, disease process evaluation and therapeutic guidance, and dual-parameter measurement may contribute to a more accurate and realistic assessment. To meet the urgent need for simultaneous detection of multiple biomarkers, we combined three-dimensional DNAzyme motors with single molecule imaging technique to construct a convenient, intuitive, and sensitive approach for the simultaneous detection of dual miRNAs in the free state or in extracellular vesicles. Quantification of target miRNAs can be realized through the detection of amplified fluorescence signals generated by the target miRNA-initiated cleavage of fluorescent substrate strands by the DNAzyme motors. The practicability was systematically validated with microRNA-21-5p and microRNA-10b-5p as targets, acquiring a satisfactory sensitivity sufficient to detect low abundance targets at 0.5 or 1 pM to 100 pM. Besides, the extracellular vesicular miRNAs can be conveniently detected without extraction. The clinical applicability was verified with a series of extracellular vesicles from clinical samples, which exhibited good distinguishability between colorectal cancer patients and healthy donors. In addition to the advantages of good specificity and high sensitivity, the system has potential to be easily adapted by minor alteration of the DNA sequences and fluorophore sets for detection of multiple miRNAs and even other types of biomarkers such as proteins. Therefore, it shows promise to be widely applied in various fields such as early diagnosis of cancer and its prognostic assessment.
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Neoplasias Colorretais , DNA Catalítico , Vesículas Extracelulares , MicroRNAs , Humanos , MicroRNAs/análise , MicroRNAs/genética , DNA Catalítico/química , DNA Catalítico/metabolismo , DNA Catalítico/genética , Vesículas Extracelulares/química , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Corantes Fluorescentes/química , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Limite de DetecçãoRESUMO
[This corrects the article DOI: 10.7150/thno.44419.].
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Background: Insomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia. Methods: This study was designed as a multicenter, randomized, sham-controlled clinical trial. A total of 264 eligible patients with breast cancer-related insomnia will be randomized into an acupuncture group and a sham acupuncture group in a 1:1 ratio. In the trial, patients in the acupuncture and sham acupuncture groups will receive 12 sessions over a consecutive 4-week period. The primary outcome will be the treatment response rate of Insomnia Severity Index (ISI) at week 4; secondary outcomes include treatment remission rate of ISI, Sleep Efficiency (SE) obtained by the use of Sleep diary, treatment response rate of ISI at 8th and 16th weeks of follow-up, the mean changes of ISI, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Questionnaire - Core 30 (QLQ-C30), sleep parameters recorded in Actigraphy and weekly usage of remedial drugs. Adverse events will be recorded throughout the study. All analyses will be based on the ITT principle and performed with SAS 9.4 statistical software. Discussion: This trial will evaluate the clinical efficacy and safety of acupuncture for breast cancer-related insomnia. If proven effective, acupuncture will provide an effective option for patients with breast cancer-related insomnia, which will play a positive role in helping patients reduce their use of sleeping medications. Clinical trial registration: ClinicalTrials.gov, identifier NCT05510700.
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Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.
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Proliferação de Células , Fatores Reguladores de Interferon , Metiltransferases , Fosfoproteínas Fosfatases , Regulação para Cima , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neovascularização Patológica/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismoRESUMO
Gene expression profiling of tissue cells with spatial context is in high demand to reveal cell types, locations, and intercellular or molecular interactions for physiological and pathological studies. With rapid advances in barcoding chemistry and sequencing chemistry, spatially resolved transcriptome (SRT) techniques have emerged to quantify spatial gene expression in tissue samples by correlating transcripts with their spatial locations using diverse strategies. These techniques provide both physical tissue structure and molecular characteristics and are poised to revolutionize many fields, such as developmental biology, neuroscience, oncology, and histopathology. In this context, this Perspective focuses on next-generation sequencing-based SRT methods, particularly highlighting spatial barcoding chemistry. It delves into optically manipulated spatial indexing methods and DNA array-barcoded spatial indexing methods by exploring current advances, challenges, and future development directions in this nascent field.
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RATIONALE AND OBJECTIVES: We examined the effectiveness of computed tomography (CT)-based deep learning (DL) models in differentiating benign and malignant solid pulmonary nodules (SPNs) ≤ 8 mm. MATERIALS AND METHODS: The study patients (n = 719) were divided into internal training, internal validation, and external validation cohorts; all had small SPNs and had undergone preoperative chest CTs and surgical resection. We developed five DL models incorporating features of the nodule and five different peri-nodular regions with the Multiscale Dual Attention Network (MDANet) to differentiate benign and malignant SPNs. We selected the best-performing model, which was then compared to four conventional algorithms (VGG19, ResNet50, ResNeXt50, and DenseNet121). Furthermore, another five DL models were constructed using MDANet to distinguish benign tumors from inflammatory nodules and the one performed best was selected out. RESULTS: Model 4, which incorporated the nodule and 15 mm peri-nodular region, best differentiated benign and malignant SPNs. The model had an area under the curve (AUC), accuracy, recall, precision, and F1-score of 0.730, 0.724, 0.711, 0.705, and 0.707 in the external validation cohort. Model 4 also performed better than the other four conventional algorithms. Model 8, which incorporated the nodule and 10 mm peri-nodular region, was the best model for distinguishing benign tumors from inflammatory nodules. The model had an AUC, accuracy, recall, precision, and F1-score of 0.871, 0.938, 0.863, 0.904, and 0.882 in the external validation cohort. CONCLUSION: The study concludes that CT-based DL models built with MDANet can accurately discriminate among small benign and malignant SPNs, benign tumors and inflammatory nodules.
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Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis. To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase ß (IKKß) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKß siRNA-loaded liposome (siIKKß-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKß-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.
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Neovascularização de Coroide , Quinase I-kappa B , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Quinase I-kappa B/genética , Quinase I-kappa B/farmacologia , Lipossomos/farmacologia , Manose , Neovascularização de Coroide/genética , Macrófagos , Terapia GenéticaRESUMO
Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.
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Proteoma , Espectrometria de Massas em Tandem , Humanos , Proteoma/metabolismo , Cromatografia Líquida , Metaboloma , Células HeLaRESUMO
To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.
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Exossomos , Proteínas de Membrana , Nucleotidiltransferases , Diester Fosfórico Hidrolases , Pirofosfatases , Transdução de Sinais , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Exossomos/metabolismo , Exossomos/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/imunologia , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Diester Fosfórico Hidrolases/metabolismo , Diester Fosfórico Hidrolases/genética , Pirofosfatases/metabolismo , Pirofosfatases/genética , Transdução de Sinais/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genéticaRESUMO
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the numerous immunohistochemical images shown in Fig. 1D on p. 2626 exhibited a number of overlaps comparing among the data panels, such that data which were intended to show the results from differently performed experiments were likely to have been derived from a smaller number of original sources. A subsequent independent investigation of the data in this paper in the Editorial Office also revealed that certain of the cell migration and invasion assay data shown in Fig. 4A on p. 2629 were strikingly similar to data that had previously appeared in a couple of already published papers written by different authors at different research institutes. Owing to the fact that the contentious data in Fig. 4 in the above article had already been published prior to its submission to Oncology Reports, in addition to the matter of several panels in Fig. 1D showing overlapping data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2624-2634, 2018; DOI: 10.3892/or.2018.6389].
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CONTEXT: Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI). OBJECTIVE: To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC-MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated. RESULTS: Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 µm vs. 14.32 ± 1.37 µm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA. DISCUSSION AND CONCLUSIONS: This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.
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Espessura Intima-Media Carotídea , Intervenção Coronária Percutânea , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Cromatografia Líquida , Simulação de Acoplamento Molecular , Farmacologia em Rede , Espectrometria de Massas em Tandem , Fator A de Crescimento do Endotélio Vascular , Constrição Patológica , MetabolômicaRESUMO
NADPH oxidases 2 (NOX2) is the main source of ROS in macrophages, which plays a critical role in the formation of atherosclerosis. However, effects of NOX2 inhibition on established vulnerable plaques and the potential role involved remain unclear. The purpose of this study is to investigate the latent mechanism of NOX2-triggered vulnerable plaque development. We generated a vulnerable carotid plaque model induced by carotid branch ligation and renal artery constriction, combined with a high-fat diet in ApoE-/- mice. NOX2 specific inhibitor, GSK2795039 (10 mg/kg/day by intragastric administration for 8 weeks) significantly prevented vulnerable plaque, evaluated by micro-ultrasound imaging parameters. A profile of less intraplaque hemorrhage detection, increased collagen-lipid ratio, fibrous cap thickness and less necrotic core formation were also found in GSK2795039 treated group. Mechanistically, reduced 4-HNE, in situ lesional apoptosis and enhanced efferocytosis were involved in mice treated with NOX2 inhibitor. Further analysis in mouse macrophages confirmed the role of NOX2 inhibition in enhancing macrophage efferocytosis by regulating the MertK/PI3K/AKT pathway. In summary, our data defined previously few recognized roles of NOX2 in vulnerable plaque pathogenesis and an undescribed NOX2-ROS-MerTK axis acts involved in regulating macrophage efferocytosis in the formation of rupture-prone vulnerable plaques.
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Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Placa Aterosclerótica/metabolismo , Macrófagos/metabolismo , ApoptoseRESUMO
MicroRNAs (miRNAs) in tumor-derived extracellular vesicles (tEVs) are important cancer biomarkers for cancer screening and early diagnosis. Multiplex detection of miRNAs in tEVs facilitates accurate diagnosis but remains a challenge. Herein, we propose an encoded fusion strategy to profile the miRNA signature in tEVs for pancreatic cancer diagnosis. A panel of encoded-targeted-fusion beads was fabricated for the selective recognition and fusion of tEVs, with the turn-on fluorescence signals of molecule beacons for miRNA quantification and barcode signals for miRNA identification using readily accessible flow cytometers. Using this strategy, six types of pancreatic-cancer-associated miRNAs can be profiled in tEVs from 2 µL plasma samples (n = 36) in an isolation-free and lysis-free manner with only 2 h of processing, offering a high accuracy (98%) to discriminate pancreatic cancer, pancreatitis, and healthy donors. This encoded fusion strategy exhibits great potential for multiplex profiling of miRNA in tEVs, offering new avenues for cancer diagnosis and screening.
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Vesículas Extracelulares , MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Vesículas Extracelulares/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Neoplasias PancreáticasRESUMO
PURPOSE: To evaluate the effects of different programmed optical zones (POZs) on achieved corneal refractive power (CRP) with myopic astigmatism after small incision lenticule extraction (SMILE). METHODS: In total, 113 patients (113 eyes) were included in this retrospective study. The eyes were divided into two groups according to POZ: group A (6.5, 6.6, and 6.7 mm, n = 59) and group B (6.8, 6.9, and 7.0 mm, n = 54). Fourier vector analysis was applied to evaluate the error values between the attempted and achieved corneal refractive power (CRP). Alpins vector analysis was used to calculate surgically induced astigmatism (SIA), difference vector (DV), magnitude of error (ME), and astigmatism correction index (ACI). Multivariate regression analysis was performed to assess potential factors associated with the error values. RESULTS: The error values in the group with large POZ were closer to zero, and significantly associated with the POZ at 2 and 4 mm of the cornea (ß = - 0.50, 95% confidence interval [CI] [- 0.80, - 0.20]; ß = - 0.37, 95% CI [- 0.63, - 0.10], P < 0.05, respectively). For the correction of astigmatism, the values of SIA, ME, and ACI were lower in group B than in group A (P < 0.05). The fitting curves between TIA and SIA were y = 0.83x + 0.19 (R2 = 0.84) and y = 1.05x + 0.04 (R2 = 0.90), respectively. CONCLUSIONS: Smaller POZs resulted in higher error values between the achieved- and attempted-CRP in the SMILE procedure, which should be considered when performing surgery.
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Astigmatismo , Cirurgia da Córnea a Laser , Miopia , Humanos , Astigmatismo/diagnóstico , Astigmatismo/etiologia , Astigmatismo/cirurgia , Refração Ocular , Acuidade Visual , Estudos Retrospectivos , Miopia/cirurgia , Córnea/cirurgia , Substância Própria/cirurgia , Lasers de Excimer/uso terapêutico , Cirurgia da Córnea a Laser/efeitos adversos , Cirurgia da Córnea a Laser/métodosRESUMO
Background: Breast cancer survivors (BCSs) are at a higher risk of developing insomnia. The negative effects of cancer-related insomnia (CRI) include depression, anxiety, fatigue, aggressive pain, impaired immune functioning, decreased quality of life, and even increased cancer mortality. Although preliminary progress has been made in the treatment of CRI with acupuncture, the evidence is insufficient and the neurological mechanism underlying the effect of acupuncture is still unclear. Methods: The study employs a single-blinded, randomized, controlled trial design. A total of 80 participants will be randomly allocated in a 1:1 ratio to either the treatment group (n = 40) or the control group (n = 40). The former will receive acupuncture treatment, while the latter will receive sham acupuncture treatment. Both groups will receive 12 sessions over a 4-week period, three times per week (every other day), and each session will last for 30 min. Follow-up assessments will be conducted in week 8. The primary outcome will be the treatment response rate. Secondary outcomes include the change in Insomnia Severity Index (ISI), the treatment remission rate, actigraphy sleep assessment, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Core Scale (QLQ-C30), the weekly usage of remedial drugs, and functional magnetic resonance imaging (fMRI) analysis. Data for the outcomes will be collected at week 0 (the baseline), week 1 (the intervention period), week 4 (the post-treatment period), and week 8 (the follow-up period). Discussion: The objective of this study is to assess the efficacy of acupuncture for patients with CRI in comparison with sham acupuncture. Additionally, the research aims to explore the neuropathological mechanisms of CRI and provide the first evidence on the characteristics of acupuncture treatment using fMRI. We expect that the results of this study will provide valuable scientific evidence of acupuncture treatment for CRI.Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2300070349: https://www.chictr.org.cn/showproj.html?proj=188677.
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Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.
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Gentamicinas , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Gentamicinas/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose , Rim , Malondialdeído/metabolismo , Glutationa/metabolismoRESUMO
Purpose: The purposes of this study were to investigate cytokine changes in the aqueous humor after treatment of acquired immune deficiency syndrome (AIDS) complicated with cytomegalovirus retinitis (CMVR) and to determine whether these changes are useful prognostic indicators. Methods: This study included 12 patients (15 eyes) undergoing treatment for AIDS and CMVR. The patients received intravitreal injections and systemic intravenous treatment with ganciclovir and foscarnet sodium. The aqueous humor of each eye was sampled before treatment and before the third and fifth injections. The samples were tested to determine the concentrations of each of 27 cytokines using the Luminex 200™ liquid phase chip. Results: The concentrations of cytokines interleukin (IL)-1rα (P = 0.002), IL-1b (P = 0.001), IL-8 (P = 0.001), basic fibroblast growth factor (bFGF) (P < 0.001), interferon γ-induced protein 10 (IP-10) (P = 0.001), and tumor necrosis factor (TNF)-α (P = 0.004) in the aqueous humor before the third and fifth injections were significantly lower after than before treatment. The reductions in TNF-α (P = 0.028) and IL-1b (P = 0.028) concentrations after treatment were statistically significant compared with the postoperative visual acuity improvement (≥3 lines and <3 lines). The difference in TNF-α (P = 0.018) level before and after treatment (the difference between before treatment and before the fifth intravitreal injection) was also statistically significant compared with the number of injections (≥6 times and <6 times). Conclusion: The cytokines IL-1rα, IL-1b, IL-8, bFGF, IP-10, and TNF-α may offer new avenues for evaluation of therapeutic effect, and TNF-α and IL-1b may be important cytokines for prognostic evaluation (based on visual acuity and the number of injections) in patients suffering from AIDS and CMVR. Clinical Trial Registration: Number: ChiCTR2200056955.
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Síndrome da Imunodeficiência Adquirida , Retinite por Citomegalovirus , Humanos , Retinite por Citomegalovirus/diagnóstico , Retinite por Citomegalovirus/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Citocinas , Fator de Necrose Tumoral alfa , Interleucina-8RESUMO
Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.
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Backgrounds: Postoperative urinary retention (POUR) is one of the most common complications after hemorrhoidectomy. The best treatment for POUR is prevention and should be involved in the whole perioperative period. Moxibustion has been used to treat urinary retention for thousands of years, and clinical studies have also proved its effects. We try to carry out a randomized, controlled, prospective study to observe whether prophylactic moxibustion could effectively reduce the incidence of POUR of hemorrhoidectomy in 24 h. Methods: This study is a single-center, evaluator-blinded, randomized, and controlled trial. Participants who meet the inclusion and exclusion criteria in this RCT will be randomly assigned to either the treatment group (moxibustion) or the control group (tamsulosin hydrochloride) in a 1:1 ratio according to a computer-generated randomization list. Both moxibustion and tamsulosin will be used 1, 10, and 24â h after operation, respectively. The outcomes of occurrence of POUR, time to first urination, catheterization rate, urinary tract infection, length of hospitalization, and adverse effects will be recorded. Discussion: The findings of the study will help to explore the preventive efficacy of prophylactic moxibustion against POUR of hemorrhoidectomy in 24 h. Trial Registration: CHiCTR, CHiCTR2000039350, registered 24 October, 2020, http://www.chictr.org.cn/showproj.aspx?proj = 63204.