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Gait and balance have emerged as a critical area of research in health technology. Gait and balance studies have been affected by the researchers' slow follow-up of research advances due to the absence of visual inspection of the study literature across decades. This study uses advanced search methods to analyse the literature on gait and balance in older adults from 1993 to 2022 in the Web of Science (WoS) database to gain a better understanding of the current status and trends in the field for the first time. The study analysed 4484 academic publications including journal articles and conference proceedings on gait and balance in older adults. Bibliometric analysis methods were applied to examine the publication year, number of publications, discipline distribution, journal distribution, research institutions, application fields, test methods, analysis theories, and influencing factors in the field of gait and balance. The results indicate that the publication of relevant research documents has been steadily increasing from 1993 to 2022. The United States (US) exhibits the highest number of publications with 1742 articles. The keyword "elderly person" exhibits a strong citation burst strength of 18.04, indicating a significant focus on research related to the health of older adults. With a burst factor of 20.46, Harvard University has made impressive strides in the subject. The University of Pittsburgh displayed high research skills in the area of gait and balance with a burst factor of 7.7 and a publication count of 103. The research on gait and balance mainly focuses on physical performance evaluation approaches, and the primary study methods include experimental investigations, computational modelling, and observational studies. The field of gait and balance research is increasingly intertwined with computer science and artificial intelligence (AI), paving the way for intelligent monitoring of gait and balance in the elderly. Moving forward, the future of gait and balance research is anticipated to highlight the importance of multidisciplinary collaboration, intelligence-driven approaches, and advanced visualization techniques.
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Bibliometría , Marcha , Equilibrio Postural , Humanos , Equilibrio Postural/fisiología , Marcha/fisiología , AncianoRESUMEN
Paramyxoviruses are important pathogens affecting various animals, including mammals and humans. Parainfluenza virus 5 (PIV5)-a member of the family Paramyxoviridae-is a major threat to the health of mammals and humans. However, studies on terrestrial wild animals infected with PIV5 are scanty. In this study, we utilized reverse transcription PCR to detect PIV5 infection in the visceral organ tissues of a Siberian tiger (Panthera tigris ssp. altaica) with vomiting, diarrhea, and dyspnea before its death. A novel PIV5 (named SR strain) with a slowly progressive cytopathic effect was isolated in Vero cells and validated using a transmission electron microscope. Full-length sequencing and analysis revealed that the whole genome of the PIV5 SR strain contained 15,246 nucleotides (nt) and seven non-overlapping genes (3'-N-V/P-M-F-SH-HN-L-5') encoding eight proteins. Phylogenetic analysis of three PIV5 strains identified in the same zoo confirmed that PIV5 strains SR and ZJQ-221 shared the closest genetic relationship as they were clustered in the same branch, while the recently found Siberian tiger strain SZ2 kept a certain distance and formed a relatively unique branch. Furthermore, mutations of nt and amino acids (aa) between strains ZJQ-221, SR, and SZ2 were identified. In summary, we report the identification and genomic characterization of a novel PIV5 strain SR isolated in a Siberian tiger, which may help future research on interspecific transmission mechanisms.
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IMPORTANCE: Respiratory syncytial virus (RSV) matrix (M) protein is indispensable for virion assembly and release. It is localized to the nucleus during early infection to perturb host transcription. However, the function of RSV M protein in other cellular activities remains poorly understood. In this study, several interferon response-associated host factors, including RACK1, were identified by proteomic analysis as RSV M interactors. Knockdown of RACK1 attenuates RSV-restricted IFN signaling leading to enhanced host defense against RSV infection, unraveling a role of M protein in antagonizing IFN response via association with RACK1. Our study uncovers a previously unrecognized mechanism of immune evasion by RSV M protein and identifies RACK1 as a novel host factor recruited by RSV, highlighting RACK1 as a potential new target for RSV therapeutics development.
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Receptores de Cinasa C Activada , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Proteínas de la Matriz Viral , Humanos , Interferones , Proteínas de Neoplasias/genética , Proteínas , Proteómica , Receptores de Cinasa C Activada/metabolismo , Infecciones por Virus Sincitial Respiratorio/metabolismo , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Proteínas de la Matriz Viral/metabolismoRESUMEN
Biotreatment of acidic rare earth mining wastewater via acidophilic living organisms is a promising approach owing to their high tolerance to high concentrations of rare earth elements (REEs); however, simultaneous removal of both REEs and ammonium is generally hindered since most acidophilic organisms are positively charged. Accordingly, immobilization of acidophilic Galdieria sulphuraria (G. sulphuraria) by calcium alginate to improve its affinity to positively charged REEs has been used for simultaneous bioremoval of REEs and ammonium. The results indicate that 97.19%, 96.19%, and 98.87% of La, Y, and Sm, respectively, are removed by G. sulphuraria beads (GS-BDs). The adsorption of REEs by calcium alginate beads (BDs) and GS-BDs is well fitted by both pseudo first-order (PFO) and pseudo second-order (PSO) kinetic models, implying that adsorption of REEs involves both physical adsorption caused by affinity of functional groups such as -COO- and -OH and chemical adsorption based on ion exchange of Ca2+ with REEs. Notably, GS-BDs exhibit high tolerance to La, Y, and Sm with maximum removal efficiencies of 97.9%, 96.6%, and 99.1%, respectively. Furthermore, the ammonium removal efficiency of GS-BDs is higher than that of free G. sulphuraria cells at an initial ammonium concentration of 100 mg L-1, while the efficiency decreases when initial concentration of ammonium is higher than 150 mg L-1. Last, small size of GS-BDs favors ammonium removal because of their lower mass transfer resistance. This study achieves simultaneous removal of REEs and ammonium from acidic mining drainage, providing a potential strategy for biotreatment of REE tailing wastewater.
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Booming graphitic carbon nitride (g-C3N4) photocatalyzed water splitting increases crisis of aquatic contamination. However, a controversial understanding regarding effect of g-C3N4 on growth of microalgae still exists. Accordingly, Chlorella vulgaris were cultured in 0-250 mg/L of g-C3N4 with biomass named as C-0, C-50, C-100, C-150, C-200, and C-250, respectively. g-C3N4 below 200 mg/L was beneficial to short-term cultivation of microalgae, while it was harmful to long-time cultivation. Protein factions of C-0, C-100, and C-250 were 41.4, 42.3, and 36.4 wt%, while their lipid factions varied from 21.5, 16.9, to 17.8 wt%, respectively. In short-term cultivation, superoxide dismutase's activity of C-0, C-150, and C-250 increased dramatically, while accumulated H2O2 led to increased activity of catalase. However, it started to decrease once antioxidant enzymes were per-oxidized, leading to increase of malondialdehyde content. In long-term cultivation, activities of superoxide dismutase, catalase and malondialdehyde content decreased dramatically owning to peroxidation of algae. Scavenger tests with tertiary butanol and triethanolamine implied that·OH was dominate parameter affecting growth of microalgae. This work indicates that g-C3N4 below 200 mg/L is propitious to short-term cultivation of microalgae, while it is bad to long-time cultivation of microalgae, revealing dual rules of g-C3N4 in Chlorella vulgaris cultivation.
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Chlorella vulgaris , Microalgas , Biomasa , Peróxido de Hidrógeno , LípidosRESUMEN
The traditional self-supported piezoelectric thin films prepared by filtration methods are limited in practical applications due to their poor tensile properties. The strategy of using flexible polyethylene terephthalate (PET) fabric as the flexible substrate is beneficial to enhancing the flexibility and stretchability of the flexible device, thus extending the applications of pressure sensors. In this work, a novel wearable pressure sensor is prepared, of which uniform and dense ZnO nanoarray-coated PET fabrics are covered by a two-dimensional MXene nanosheet. The ternary structure incorporates the advantages of the three components including the superior piezoelectric properties of ZnO nanorod arrays, the excellent flexibility of the PET substrate, and the outstanding conductivity of MXene, resulting in a novel wearable sensor with excellent pressure-sensitive properties. The PET/ZnO@MXene pressure sensor exhibits excellent sensing performance (S = 53.22 kPa-1), fast response/recovery speeds (150 ms and 100 ms), and superior flexural stability (over 30 cycles at 5% strain). The composite fabric also shows high sensitivity in both motion monitoring and physiological signal detection (e.g., device bending, elbow bending, finger bending, wrist pulse peaks, and sound signal discrimination). These findings provide insight into composite fabric-based pressure-sensitive materials, demonstrating the great significance and promising prospects in the field of flexible pressure sensing.
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Tereftalatos Polietilenos , Óxido de Zinc , Textiles , Fenómenos FísicosRESUMEN
Consumer testing assays a panel's liking of a food or other sensory stimulus. However, liking can be influenced by mood, with people feeling more uncomfortable, or more unhappy reporting lower liking ratings than those in a higher affect. Though consumer testing typically takes place as a central location test (CLT, usually in a set of standardized sensory booths), the COVID-19 pandemic has resulted in a global pivot to home use tests (HUTs), where panelists can taste and smell samples unmasked more safely while in their own homes. Unfortunately, as this situation differs in many ways to a central location test, this puts the validity of longitudinal comparisons of liking scores under question. Further, as people across the globe report feelings of worry, unease, and stress during the pandemic, this may present a second source of variation in affect with previous years. We tested a set of snack bar samples both at home and in a central location, in repeated measures with the same panel, to test the validity of comparisons across locations. We further compared CLT results to those when testing the same samples in a previous year. Finally, we performed a meta-analysis of existing data on this subject. While liking behavior in CLTs did not differ between years, panelists rated some samples higher when in their own homes, in line with results from the meta-analysis of previous reports. Interestingly, panelists in the study also assigned fewer penalties in the HUT, implying a less analytical mindset when in the home. Results suggest that care should be taken when comparing results taken at home during the COVID-19 pandemic to those taken previously in a central location. PRACTICAL APPLICATION: Consumer testing is applied in the food industry to evaluate a panelist's liking for a food product or stimulus. However, liking is also dependent on factors extrinsic to the samples tested. Thus, with the switch to in-home testing due to COVID-19, we compared liking scores from in-home and central locations testing, with higher scores common in HUTs.
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COVID-19 , Comportamiento del Consumidor , Vivienda , Pandemias , Distanciamiento Físico , Adolescente , Adulto , Anciano , COVID-19/epidemiología , Preferencias Alimentarias , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Reproducibilidad de los Resultados , Olfato , Gusto , Adulto JovenRESUMEN
Bio-removal of negative charged platinum complex is of great challenge owing to electrostatic repulsions between PtCl62- and general extracellular polymeric substance (EPS) of microorganism. Galdieria sulphuraria (GS) are thermophilic and acidophilic microalga with specific metabolism, which subsequently lead to their unique cellular compositions such as EPS and phycocyanin, possibly providing a strategy to deal with negative charged metal complex. Accordingly, G. sulphuraria are employed to remove negative charged PtCl62- complex with initial concentrations ranging from 0, 10, 20, 30, to 45 ppm. The growth rates of G. sulphuraria with microalgae named as GS-0, GS-10, GS-20, GS-30, and GS-45, respectively, and simultaneously bio-removal efficiencies of PtCl62- are investigated. G. sulphuraria are independent to PtCl62- within 0-30 ppm, while they are inhibited within 45 ppm of PtCl62-. The PtCl62- removal efficiencies of GS-10, GS-20, and GS-30 increase from 94.58%, 95.52%, to 95.92%, while decrease to 71.81% of GS-45. About 92.39%, 93.77%, 94.29%, and 75.21% of PtCl62- adsorbed are accumulated within GS-10, GS-20, GS-30, GS-45, with few in EPS. The PtCl62- complexes accumulated in EPS and algae cells are possibly decomposed to PtCl4 according to the increasing zeta potentials of EPS and algae cells. The results indicate that PtCl62- is efficiently removed by G. sulphuraria, achieving bio-removal of negative charged PtCl62- complex from wastewater.
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Microalgas , Rhodophyta , Matriz Extracelular de Sustancias Poliméricas , Ficocianina , Aguas ResidualesRESUMEN
Alcohol drinking has been established as a major risk factor for esophageal diseases. Our previous study showed that ethanol exposure inhibited PAX9 expression in human esophageal squamous epithelial cells in vitro and in vivo. In this study, we aimed to investigate the molecular pathways through which alcohol drinking suppresses PAX9 in esophageal squamous epithelial cells. We first demonstrated the inhibition of NOTCH by ethanol exposure in vitro. NOTCH regulated PAX9 expression in KYSE510 and KYSE410 cells in vitro and in vivo. RBPJ and NOTCH intracellular domain (NIC) D1 ChIP-PCR confirmed Pax9 as a direct downstream target of NOTCH signaling in mouse esophagus. NOTCH inhibition by alcohol drinking was further validated in mouse esophagus and human tissue samples. In conclusion, ethanol exposure inhibited NOTCH signaling and thus suppressed PAX9 expression in esophageal squamous epithelial cells in vitro and in vivo. Our data support a novel mechanism of alcohol-induced esophageal injury through the inhibition of NOTCH-PAX9 signaling. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma de Células Escamosas de Esófago/patología , Factor de Transcripción PAX9/efectos de los fármacos , Receptores Notch/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Animales , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Etanol/toxicidad , Humanos , Ratones , Factor de Transcripción PAX9/metabolismo , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
BACKGROUND: Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. SUBJECTS, MATERIALS, AND METHODS: We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. RESULTS: Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort. CONCLUSION: This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD. IMPLICATIONS FOR PRACTICE: Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.
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Enfermedad de Castleman , Herpesvirus Humano 8 , Adulto , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/tratamiento farmacológico , China , Humanos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify risk factors associated with surgical site infection (SSI) after major oral oncological surgery. METHODS: This retrospective study reviewed data from patients that underwent major surgery for oral cancer at a tertiary referral hospital in China between January 2005 and July 2016. SSI was diagnosed within 30 days. Demographic, cancer-related, preoperative, perioperative and postoperative data were analysed using descriptive statistics and univariate and multivariate analyses of the risk factors for SSI. RESULTS: A total of 786 patients were enrolled, of whom 125 had SSI (15.9%), which were all incisional. Independent risk factors for SSI, identified by multivariate analysis, were diabetes mellitus (odds ratio [OR] 2.147, 95% confidence interval [CI] 1.240, 3.642), prior radiotherapy (OR 4.595, 95% CI 1.293, 17.317) and oral-neck communication (OR 2.838, 95% CI 1.263, 7.604); and factors reflecting large extent resections were tracheostomy (OR 2.235, 95% CI 1.435, 3.525), anterolateral thigh flap (OR 1.971, 95% CI 1.103, 3.448) and latissimus dorsi flap (OR 4.178, 95% CI 1.325, 13.189). CONCLUSIONS: Multiple risk factors were associated with SSI after major oral oncological surgery. To minimize SSI risk, surgeons managing oral cancer patients should have a better understanding of the risk factors, including diabetes mellitus, prior radiotherapy, tracheostomy, oral-neck communication and flap reconstruction.
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Infección de la Herida Quirúrgica , China/epidemiología , Humanos , Estudios Retrospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Centros de Atención TerciariaRESUMEN
Development of novel activable dual-mode T1/T2-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we demonstrated a strategy to prepare clustered Fe3O4 nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T2/T1-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe3O4 NPs with an average size of 3.3 nm and an r1 relaxivity of 4.3 mM-1 s-1, and then cross-linked the single Fe3O4 NPs using cystamine dihydrochloride (Cys) to form clustered Fe3O4/Cys NPs. The Fe3O4 nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high r2 relaxivity (26.4 mM-1 s-1), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe3O4 NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T2/T1-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells in vitro and a subcutaneous tumor model in vivo due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T2 to T1 MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe3O4 NCs may be used as a promising switchable T2/T1 dual-mode MR contrast agent for precision imaging of different biosystems.
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Nanopartículas Magnéticas de Óxido de Hierro/análisis , Imagen por Resonancia Magnética/métodos , Neoplasias/diagnóstico por imagen , Animales , Línea Celular , Disulfuros/análisis , Nanopartículas Magnéticas de Óxido de Hierro/ultraestructura , Ratones , Nanotecnología , Oxidación-ReducciónRESUMEN
The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core-shell tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and ß-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host-guest recognition and pH-responsiveness of BM/ß-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.
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Antineoplásicos/química , Dendrímeros/química , Doxorrubicina/química , Portadores de Fármacos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Bencimidazoles/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Liberación de Fármacos , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , beta-Ciclodextrinas/químicaRESUMEN
Sirtuin 3 (Sirt3)-modified mitochondrial fission participates in the progression of several types of cancers. However, its role in tongue cancer requires investigation. The aim of our study is to determine whether Sirt3 knockdown regulates the viability of tongue cancer cells via modulating mitochondrial fission. Two types of tongue cancer cells were used in the present study, and siRNA was transfected into the cells to suppress Sirt3 expression. Mitochondrial function and cell apoptosis were determined via immunofluorescence, Western blotting, ELISA, and qPCR assays. A pathway blocker was applied to verify the role of the JNK-Fis1 signaling pathway in regulation of mitochondrial fission. The present study showed that loss of Sirt3 promoted tongue cancer cell death in a manner dependent on mitochondrial apoptosis. Mitochondrial oxidative stress, energy metabolism disorder, mitochondrial cyt-c liberation, and mitochondrial apoptosis activation were observed after Sirt3 silencing. Furthermore, we demonstrated that Sirt3 knockdown activated mitochondrial stress via triggering Fis1-related mitochondrial fission and that inhibition of Fis1-related mitochondrial fission abrogated the pro-apoptotic effect of Sirt3 knockdown on tongue cancer cells. To this end, we found that Sirt3 modulated Fis1 expression via the c-Jun N-terminal kinases (JNK) signaling pathway and that blockade of the JNK pathway attenuated mitochondrial stress and repressed apoptosis in Sirt3 knockdown cells. Altogether, our results identified a tumor-suppressive role for Sirt3 deficiency in tongue cancer via activation of the JNK-Fis1 axis and subsequent initiation of fatal mitochondrial fission. Given these findings, strategies to repress Sirt3 activity and enhance the JNK-Fis1-mitochondrial fission cascade have clinical benefits for patients with tongue cancer.
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Carcinoma de Células Escamosas/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas de la Membrana/metabolismo , Dinámicas Mitocondriales , Proteínas Mitocondriales/metabolismo , Sirtuina 3/metabolismo , Estrés Fisiológico , Neoplasias de la Lengua/patología , Apoptosis , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas , Mitocondrias/metabolismo , Sirtuina 3/antagonistas & inhibidores , Sirtuina 3/genéticaRESUMEN
The development of a powerful nanoplatform to realize the simultaneous therapy and diagnosis of cancer using a similar element for theranostics remains a critical challenge. Herein, we report such a theranostic nanoplatform based on pyridine (Pyr)-functionalized generation 5 (G5) poly(amidoamine) dendrimers complexed with copper(II) (Cu(II)) for radiotherapy-enhanced T1-weighted magnetic resonance (MR) imaging and the synergistic radio-chemotherapy of both tumors and tumor metastasis. In this study, amine-terminated G5 dendrimers were covalently linked with 2-pyridinecarboxylic acid, acetylated to neutralize their remaining terminal amines, and complexed with Cu(II) through both the internal tertiary amines and the surface Pyr groups to form the G5.NHAc-Pyr/Cu(II) complexes. We show that the complexes are able to inhibit the proliferation of different cancer cell lines with half-maximal inhibitory concentrations ranging from 4 to 10 µM and induce significant cancer cell apoptosis. Due to the presence of Cu(II), the G5.NHAc-Pyr/Cu(II) complexes display an r1 relaxivity of 0.7024 mM-1 s-1, enabling effective in vivo MR imaging of tumor xenografts and lung metastatic nodules. Further, under radiotherapy (RT) conditions, the tumor MR imaging sensitivity can be significantly enhanced, and the G5.NHAc-Pyr/Cu(II) complexes enable the enhanced chemotherapy of both a xenografted tumor model and a blood-vessel metastasis model. With the demonstrated theranostic potential of the dendrimer-Cu(II) nanocomplexes without additional agents or elements for RT-enhanced MR imaging and chemotherapy of tumor and tumor metastasis, this novel Cu(II)-based nanohybrids may hold great promise for the theranostics of different cancer types and metastases.
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Polydopamine-coated magnetic mesoporous silica nanoparticles have been designed by loading ultrasmall iron oxide nanoparticles within hollow mesoporous silica nanopartricles and then coating polydopamine onto the particle surface. The developed nanoplatform displayed improved colloidal stability, enhanced r1 relaxivity and near infrared absorption feature, affording their use for multimodal cancer theranostics.
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Antineoplásicos/farmacología , Indoles/química , Nanopartículas de Magnetita/química , Neoplasias Mamarias Animales/tratamiento farmacológico , Polímeros/química , Dióxido de Silicio/química , Nanomedicina Teranóstica , Animales , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Neoplasias Mamarias Animales/patología , Ratones , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
Noninvasive physical treatment with relatively low intensity stimulation and the development of highly efficient anticancer medical strategy are still desirable for cancer therapy. Herein a versatile, biodegradable, hollow mesoporous organosilica nanocapsule (HMONs) nanoplatform that is capped by the gemcitabine (Gem) molecule through a pH-sensitive acetal covalent bond is designed. The fabricated nanocapsule exhibits desirable small molecule release at the tumor tissues/cell sites and shows a reduced risk for drug accumulation. After loading indocyanine green (ICG), the heat-shock protein 90 (Hsp 90) inhibitor, and 17AAG and modification with polyethylene glycol (NH2-PEG), the resulting ICG-17AAG@HMONs-Gem-PEG exhibited a precisely controlled release of ICG and 17AAG and low-temperature photothermal therapy (PTT) (â¼41 °C) with excellent tumor destruction efficacy. In addition, ICG loading conferred the nanoplatform with near-infrared fluorescence imaging (FL) and photoaccoustic (PA) imaging capability. In short, this work not only presents a smart drug self-controlled nanoplatform with pH-responsive payload release and theranostic performance but also provides an outstanding low-temperature PTT strategy, which is highly valid in the inhibition of cancer cells with minimal damage to the organism. Therefore, this research provides a paradigm that has a chemodrug-gated HMONs-based theranostic nanoplatform with intrinsic biodegradability, multimodal imaging capacity, high low-temperature PTT/chemotherapy efficacy, and reduced systemic toxicity.