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BACKGROUND: There are no recent studies comparing the compliance rates of both patients and observers in tuberculosis treatment between the video-observed therapy (VOT) and directly observed therapy (DOT) programs. OBJECTIVE: This study aims to compare the average number of days that patients with pulmonary tuberculosis and their observers were compliant under VOT and DOT. In addition, this study aims to compare the sputum conversion rate of patients under VOT with that of patients under DOT. METHODS: Patient and observer compliance with tuberculosis treatment between the VOT and DOT programs were compared based on the average number of VOT and DOT compliance days and sputum conversion rates in a 60-day cluster randomized controlled trial with patients with pulmonary tuberculosis (VOT: n=63 and DOT: n=65) with positive sputum acid-fast bacilli smears and 38 observers equally randomized into the VOT and DOT groups (19 observers per group and n=1-5 patients per observer). The VOT group submitted videos to observers via smartphones; the DOT group followed standard procedures. An intention-to-treat analysis assessed the compliance of both the patients and the observers. RESULTS: The VOT group had higher average compliance than the DOT group (patients: mean difference 15.2 days, 95% CI 4.8-25.6; P=.005 and observers: mean difference 21.2 days, 95% CI 13.5-28.9; P<.001). The sputum conversion rates in the VOT and DOT groups were 73% and 61.5%, respectively (P=.17). CONCLUSIONS: Smartphone-based VOT significantly outperformed community-based DOT in ensuring compliance with tuberculosis treatment among observers. However, the study was underpowered to confirm improved compliance among patients with pulmonary tuberculosis and to detect differences in sputum conversion rates. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR) TCTR20210624002; https://tinyurl.com/3bc2ycrh. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/38796.
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Terapia por Observación Directa , Teléfono Inteligente , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Teléfono Inteligente/instrumentación , Teléfono Inteligente/estadística & datos numéricos , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Cumplimiento y Adherencia al Tratamiento/psicología , Cooperación del Paciente/estadística & datos numéricos , Tuberculosis Pulmonar/terapia , Tuberculosis Pulmonar/tratamiento farmacológico , Análisis por ConglomeradosRESUMEN
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.
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Clorofilidas , Nanogeles , Neoplasias , Óxido Nítrico , Porfirinas , Animales , Óxido Nítrico/administración & dosificación , Óxido Nítrico/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/metabolismo , Porfirinas/administración & dosificación , Porfirinas/farmacocinética , Línea Celular Tumoral , Nanogeles/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Polietilenglicoles/química , Ratones Desnudos , Polietileneimina/química , Ratones Endogámicos BALB C , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Femenino , Ratones , Terapia por Ultrasonido/métodos , Nanoestructuras/administración & dosificaciónRESUMEN
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
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Lesión Pulmonar Aguda , Cerio , Indoles , Polímeros , Especies Reactivas de Oxígeno , Cerio/química , Cerio/farmacología , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Polímeros/química , Polímeros/farmacología , Indoles/química , Indoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Ratones , Masculino , Células RAW 264.7 , Pulmón/efectos de los fármacos , Pulmón/patología , Antioxidantes/farmacología , Antioxidantes/química , Ratas Sprague-Dawley , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Rayos Infrarrojos , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/uso terapéutico , Nanopartículas/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Citocinas/metabolismoRESUMEN
Social deficits are debilitating features of many psychiatric disorders, including autism. While time-intensive behavioral therapy is moderately effective, there are no pharmacological interventions for social deficits in autism. Many studies have attempted to treat social deficits using the neuropeptide oxytocin for its powerful neuromodulatory abilities and influence on social behaviors and cognition. However, clinical trials utilizing supplementation paradigms in which exogenous oxytocin is chronically administered independent of context have failed. An alternative treatment paradigm suggests pharmacologically activating the endogenous oxytocin system during behavioral therapy to enhance the efficacy of therapy by facilitating social learning. To this end, melanocortin receptor agonists like Melanotan II (MTII), which induces central oxytocin release and accelerates formation of partner preference, a form of social learning, in prairie voles, are promising pharmacological tools. To model pharmacological activation of the endogenous oxytocin system during behavioral therapy, we administered MTII prior to social interactions between male and female voles. We assessed its effect on oxytocin-dependent activity in brain regions subserving social learning using Fos expression as a proxy for neuronal activation. In non-social contexts, MTII only activated hypothalamic paraventricular nucleus, a primary site of oxytocin synthesis. However, during social interactions, MTII selectively increased oxytocin-dependent activation of nucleus accumbens, a site critical for social learning. These results suggest a mechanism for the MTII-induced acceleration of partner preference formation observed in previous studies. Moreover, they are consistent with the hypothesis that pharmacologically activating the endogenous oxytocin system with a melanocortin agonist during behavioral therapy has potential to facilitate social learning.
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Núcleo Accumbens , Oxitocina , Masculino , Humanos , Femenino , Animales , Oxitocina/metabolismo , Núcleo Accumbens/metabolismo , Melanocortinas/metabolismo , Conducta Social , Receptores de Oxitocina/metabolismo , Medio Social , Arvicolinae/fisiologíaRESUMEN
Biofilms offer bacteria a physical and metabolic barrier, enhancing their tolerance to external stress. Consequently, these biofilms limit the effectiveness of conventional antimicrobial treatment. Recently, quorum sensing (QS) has been linked to biofilm's stress response to thermal, oxidative, and osmotic stress. Herein, a multiple synergistic therapeutic strategy that couples quorum sensing interference assisted therapy (QSIAT)-mediated enhanced thermal therapy with bacteria-triggered immunomodulation in a single nanoplatform, is presented. First, as magnetic hyperthermia amplifier, hyaluronic acid-coated ferrite (HA@MnFe2 O4 ) attenuates the stress response of biofilm by down-regulating QS-related genes, including agrA, agrC, and hld. Next, the sensitized bacteria are eliminated with magnetic heat. QS interference and heat also destruct the biofilm, and provide channels for further penetration of nanoparticles. Moreover, triggered by bacterial hyaluronidase, the wrapped hyaluronic acid (HA) decomposes into disaccharides at the site of infection and exerts healing effect. Thus, by reversing the bacterial tissue invasion mechanism for antimicrobial purpose, tissue regeneration following pathogen invasion and thermal therapy is successfully attained. RNA-sequencing demonstrates the QS-mediated stress response impairment. In vitro and in vivo experiments reveal the excellent antibiofilm and anti-inflammatory effects of HA@MnFe2 O4 . Overall, QSIAT provides a universal enhancement strategy for amplifying the bactericidal effects of conventional therapy via stress response interference.
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Hipertermia Inducida , Percepción de Quorum , Ácido Hialurónico , Biopelículas , Antibacterianos/farmacología , Bacterias , Fenómenos MagnéticosRESUMEN
Metal-based nanomaterials have attracted broad attention recently due to their unique biological physical and chemical properties after entering tumor cells, namely biological effects. In particular, the abilities of Ca2+ to modulate T cell receptors activation, K+ to regulate stem cell differentiation, Mn2+ to activate the STING pathway, and Fe2+/3+ to induce tumor ferroptosis and enhance catalytic therapy, make the metal ions and metal-based nanomaterials play crucial roles in the cancer treatments. Therefore, due to the superior advantages of metal-based nanomaterials and the characteristics of the tumor microenvironment, we will summarize the recent progress of the anti-tumor biological effects of metal-based nanomaterials. Based on the different effects of metal-based nanomaterials on tumor cells, this review mainly focuses on the following five aspects: (1) metal-enhanced radiotherapy sensitization, (2) metal-enhanced catalytic therapy, (3) metal-enhanced ferroptosis, (4) metal-enhanced pyroptosis, and (5) metal-enhanced immunotherapy. At the same time, the shortcomings of the biological effects of metal-based nanomaterials on tumor therapy are also discussed, and the future research directions have been prospected. The highlights of promising biosafety, potent efficacy on biological effects for tumor therapy, and the in-depth various biological effects mechanism studies of metal-based nanomaterials provide novel ideas for the future biological application of the nanomaterials.
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BACKGROUND: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. METHODS: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a fourfold decline in RPR titers at month 12. RESULTS: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P= .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% CI, 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12. CONCLUSIONS: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.
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BACKGROUND: The health care system in Thailand has struggled to cope with the COVID-19 pandemic, resulting in decreased administration of community-based directly observed therapy (DOT) for tuberculosis (TB). As an alternative to failed DOT, video-observed therapy (VOT) or the Thai asynchronous VOT system, "TH VOT," was devised. We developed a protocol for a study to test the superiority of VOT over DOT in ensuring treatment compliance. OBJECTIVE: We aim to compare the mean cumulative compliance days of TB patients and their observers under the VOT program with that of individuals under the DOT program during the intensive phase of TB treatment. METHODS: A cluster randomized controlled trial of pulmonary TB patients and their observers will be conducted over a 2-month period. This study will be conducted in the Hat Yai and Meuang Songkhla districts of Songkhla Province, Southern Thailand. A total of 38 observers working at 38 primary care units (PCUs) will be randomized equally into VOT and DOT groups. The TH VOT system will be implemented in 19 PCUs in the VOT group while the other 19 PCUs will continue with the traditional DOT program. Approximately 1-5 TB patients will be under observation, depending on the PCU jurisdiction in which the patients reside. The inclusion criteria for TB patients will be as follows: patients diagnosed with newly active pulmonary TB with a positive acid-fast bacilli sputum smear, aged >18 years, own a smartphone, and are able to use the LINE (Line Corporation) app. The exclusion criteria will be patients with a condition that requires the intervention of a specialist, rifampicin resistance according to a cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF), unable to continue the treatment, and/or alcohol dependence. After the 2-month observation period, all sessions and follow-up clinical outcomes recorded will be retrieved. An intention-to-treat analysis will be performed to assess the compliance of both patients undergoing drug administration and their observers. RESULTS: The Human Research Ethics Committee, Faculty of Medicine, Prince of Songkla University approved the trial on February 19, 2021 (approval number 64-03618-9). The trial was funded in May 2021. The recruitment period will be from January 2022 to July 2022. The observation is scheduled to end by September 2022. CONCLUSIONS: If the VOT shows superiority in observational compliance among patients and observers, the existing DOT policy will be replaced with VOT. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210624002; https://www.thaiclinicaltrials.org/show/TCTR20210624002. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38796.
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BACKGROUND: In Thailand, the health care system has struggled to cope with COVID-19, resulting in directly observed therapy for tuberculosis being de-emphasized. A video-observed therapy (VOT) system, or more specifically, the Thai VOT (TH VOT) system, was developed to replace directly observed therapy. According to the pilot study, the system needed notifications to improve usability and user compliance. The updated version of the TH VOT system thus enabled LINE (Line Corporation) notifications. OBJECTIVE: This study aimed to reassess users' compliance with and the usability of the updated TH VOT system. METHODS: This study was conducted in the Hat Yai and Mueang Songkhla districts in Songkhla Province, Southern Thailand, from September 18 to December 1, 2021. The system was used by not only patients with tuberculosis but also tuberculosis staff, who acted as observers in primary health care settings. Some of the observers used the simulated VOT system instead of the actual system due to the lack of participating patients in their jurisdiction. After 30 days of using the system, VOT session records were analyzed to determine the compliance of the patients and observers. The User Experience Questionnaire was administered to reassess the usability of the system and compare the ratings of the participants with the general benchmark scores of the User Experience Questionnaire. The results were summarized to reveal the degree of user compliance and usability in the following three groups: the patients, actual VOT observers, and simulated VOT observers. RESULTS: Of the 19 observers, 10 used the actual VOT system, and the remaining 9 used the simulated VOT system; there were also 10 patients with tuberculosis. The patients, actual VOT observers, and simulated VOT observers exhibited about 70%, 65%, and 50% compliance, respectively, in terms of following the standard operating procedures every day. The scores of all groups on all dimensions were well above the average scores. There was no significant difference in any of the dimensional scores among the three groups. CONCLUSIONS: The updated version of the TH VOT system was deemed usable by both the patients and the health care staff. Compliance with the use of the system was high among the patients but moderate among the observers.
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The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations-SonoVue®, Sonazoid™, and Optison™-were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh-Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.
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BACKGROUND: Directly observed therapy programs for monitoring tuberculosis (TB) treatment in Thailand are unsustainable, especially during the COVID-19 pandemic. The current video-observed therapy (VOT) system, the Thai VOT (TH VOT), was developed to replace the directly observed therapy program. OBJECTIVE: This study aimed to describe the VOT system design and identify the potential for system improvements. METHODS: This pilot study was conducted in Na Yong district, a small district in Trang province, south of Thailand. The TH VOT system consists of a smartphone app for patients, a secured web-based platform for staff, items used, and standard operating procedures. There were three groups of users: observers who were TB staff, healthy volunteers as simulated patients, and patients with active TB. All participants were trained to follow the standard operating procedures. After 2-week usage, VOT session records were analyzed to measure the compliance of the patients and observers. The User Experience Questionnaire was used to lead the participant users to focus on 6 standard dimensions of usability, and was supplemented with an in-depth interview to identify potential system improvements from users' experience. RESULTS: Only 2 of 16 patients with currently active TB had a usable smartphone. Sixty of 70 drug-taking sessions among 2 patients and 3 simulated patients in 2 weeks were recorded and uploaded. Only 37 sessions were inspected by the observers within 24 hours. All participants needed a proper notification system. An audit system was also requested. CONCLUSIONS: Before upscaling, the cost of smartphone lending, audit management, and notification systems should be elucidated.
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Reactive oxygen species (ROS)-related therapeutic approaches are developed as a promising modality for cancer treatment because the aberrant increase of intracellular ROS level can cause cell death due to nonspecific oxidation damage to key cellular biomolecules. However, the most widely considered strategy, photodynamic therapy (PDT), suffers from critical limitations such as limited tissue-penetration depth, high oxygen dependence, and phototoxicity. Non-photo-induced ROS generation strategies, which are defined as Xdynamic therapies (X = sono, radio, microwave, chemo, thermo, and electro), show good potential to overcome the drawbacks of PDT. Herein, recent advances in the development of Xdynamic therapies, including the design of systems, the working mechanisms, and examples of cancer therapy application, are introduced. Furthermore, the approaches to enhance treatment efficiency of Xdynamic therapy are highlighted. Finally, the perspectives and challenges of these strategies are also discussed.
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Fotoquimioterapia , Línea Celular Tumoral , Humanos , Fármacos Fotosensibilizantes , Especies Reactivas de OxígenoRESUMEN
Ulcerative colitis (UC) is a modern refractory disease with steadily increasing incidence worldwide that urgently requires effective and safe therapies. Therapeutic peptides delivered using nanocarriers have shown promising developments for the treatment of UC. We developed a novel colon-accumulating oral drug delivery nanoplatform consisting of Musca domestica cecropin (MDC) and mesoporous carbon nanoparticles (MCNs) and investigated its effects and mechanism of action for the treatment of UC. Methods: An optimized one-step soft templating method was developed to synthesize MCNs, into which MDC was loaded to fabricate MDC@MCNs. MCNs and MDC@MCNs were characterized by BET, XRD, and TEM. MDC and MDC@MCNs resistance to trypsin degradation was measured through Oxford cup antibacterial experiments using Salmonella typhimurium as the indicator. Uptake of MDC and MDC@MCNs by NCM460 cells was observed by fluorescence microscopy. The biocompatibility of MDC, MCNs, and MDC@MCNs was evaluated in three cell lines (NCM460, L02, and NIH3T3) and C57BL/6 mice. Dextran sulphate sodium was used to establish models of NCM460 cell injury and UC in mice. MTT assay, flow cytometry, and mitochondrial membrane potential assay were applied to determine the effects of MDC@MCNs on NCM460 cells injury. Additionally, a variety of biological methods such as H&E staining, TEM, ELISA, qPCR, Western blotting, and 16s rDNA sequencing were performed to explore the effects and underlying mechanism of MDC@MCN on UC in vivo. Colonic adhesion of MCNs was compared in normal and UC mice. The oral biodistributions of MDC and MDC@MCNs in the gastrointestinal tract of mice were also determined. Results: MDC@MCNs were successfully developed and exhibited excellent ability to resist destruction by trypsin and were taken up by NCM460 cells more readily than MDC. In vitro studies showed that MDC@MCNs better inhibited DSS-induced NCM460 cells damage with lower toxicity to L02 and NIH3T3 cells compared with MDC. In vivo results indicated that MDC@MCNs have good biocompatibility and significantly improved colonic injury in UC mice by effectively inhibiting inflammation and oxidative stress, maintaining colonic tight junctions, and regulating intestinal flora. Moreover, MDC@MCNs were strongly retained in the intestines, which was attributed to intestinal adhesion and aggregation of MCNs, serving as one of the important reasons for its enhanced efficacy after oral administration compared with MDC. Conclusion: MDC@MCNs alleviated DSS-induced UC by ameliorating colonic epithelial cells damage, inhibiting inflammation and oxidative stress, enhancing colonic tight junctions, and regulating intestinal flora. This colon-accumulating oral drug delivery nanoplatform may provide a novel and precise therapeutic strategy for UC.
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Antiinflamatorios/farmacología , Cecropinas/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Administración Oral , Animales , Antiinflamatorios/farmacocinética , Carbono/química , Carbono/farmacocinética , Cecropinas/farmacocinética , Línea Celular , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Femenino , Moscas Domésticas/química , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Nanopartículas/metabolismo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Dodecil Sulfato de Sodio/administración & dosificaciónRESUMEN
Ultrasound (US)-induced sonodynamic therapy (SDT) is an efficient and precise method against tumor, and the integration of multiple cancer therapies has been proved as a promising strategy for better therapeutic effects. Herein, for the first time, a multifunctional nanoreactor has been fabricated by integrating Fe-MIL-88B-NH2, PFC-1, and glucose oxidase (GOx) to form urchin-like Fe-MIL-88B-NH2@PFC-1-GOx (MPG) nanoparticles as Fenton's reagent, a sonosensitizer, and a tumor microenvironment (TME) modulator. In detail, MPG can generate â¢OH for chemodynamic therapy (CDT) and deplete glutathione (GSH) to alleviate the antioxidant ability of cancer cells. Moreover, catalase (CAT)-like MPG can react with H2O2 to generate O2 for relieving hypoxia in TME, enhancing GOx-catalyzed glucose oxidation to produce H2O2 and gluconic acid. Then, the regenerated H2O2 can promote the Fenton reaction to achieve GOx catalysis-enhanced CDT. Owing to its large π-electron conjugated system, MPG also serves as an ideal sonosensitizer, realizing a burst generation of 1O2 under US irradiation for efficient SDT. Therefore, the tumor treatment will be notably enhanced by MPG-based synergetic CDT/SDT/starvation therapy via a series of cascade reactions. Overall, this work develops a versatile nanoreactor with improved tumor treatment effectiveness and broadens the application prospects of porous materials in the field of biomedical research.
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Glucosa Oxidasa/uso terapéutico , Neoplasias Mamarias Animales/terapia , Estructuras Metalorgánicas/uso terapéutico , Nanocompuestos/uso terapéutico , Animales , Biocatálisis , Catálisis , Línea Celular Tumoral , Femenino , Glucosa Oxidasa/química , Glutatión/metabolismo , Enlace de Hidrógeno , Peróxido de Hidrógeno/metabolismo , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Estructuras Metalorgánicas/química , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Nanocompuestos/química , Nanocompuestos/ultraestructura , Nanomedicina , Hipoxia Tumoral/efectos de los fármacos , Terapia por UltrasonidoRESUMEN
Background: Traumatic experiences may result in Posttraumatic Stress Disorder (PTSD), which is characterized as an exaggerated fear response that cannot be extinguished over time or in safe environments. What are beneficial psychotherapeutic treatment options for PTSD patients? Can oxytocin (OXT), which is involved in the stress response, and safety learning, ameliorate PTSD symptomatology and enhance psychotherapeutic effects? Here, we will review recent studies regarding OXT's potential to enhance psychotherapeutic therapies for PTSD treatment. Method: We conducted a literature review on the neurobiological underpinnings of PTSD especially focusing on OXT's involvement in the biology and memory formation of PTSD. Furthermore, we researched successful psychotherapeutic treatments for PTSD patients and discuss how OXT may facilitate observed psychotherapeutic effects. Results: For a relevant proportion of PTSD patients, existing psychotherapies are not beneficial. OXT may be a promising candidate to enhance psychotherapeutic effects, because it dampens responses to stressful events and allows for a faster recovery after stress. On a neural basis, OXT modulates processes that are involved in stress, arousal and memory. OXT effectively counteracts memory impairments caused by stress and facilitates social support seeking which is a key resilience factor for PTSD and which is beneficial in psychotherapeutic settings. Conclusion: OXT has many characteristics that are promising to positively influence psychotherapy for PTSD patients. It potentially reduces intrusions, but preserves memory of the event itself. Introducing OXT into psychotherapeutic settings may result in better treatment outcomes for PTSD patients. Future research should directly investigate OXT's effects on PTSD, especially in psychotherapeutic settings.
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PURPOSE: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. METHODS: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). RESULTS: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. CONCLUSION: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.
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Carcinoma Hepatocelular/tratamiento farmacológico , Dendrímeros/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/administración & dosificación , Sorafenib/administración & dosificación , Animales , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/patología , Dendrímeros/farmacocinética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Ratones , Nanopartículas/química , Polímeros/química , Polímeros/farmacocinética , Vitamina E/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Two-dimensional (2D) MXenes have emerged as a promising planar theranostic nanoplatform for versatile biomedical applications; but their in vivo behavior and performance has been severely influenced and hindered by a lack of necessary surface chemistry for adequate surface engineering. To solve this critical issue, this work employs versatile sol-gel chemistry for the construction of a unique "therapeutic mesopore" layer onto the surface of 2D niobium carbide (Nb2C) MXene. Methods: The in situ self-assembled mesopore-making agent (cetanecyltrimethylammonium chloride, in this case) was kept within the mesopores for efficient chemotherapy. The abundant surface saline chemistry of mesoporous silica-coated Nb2C MXene was further adopted for stepwise surface engineering including PEGylation and conjugation with cyclic arginine-glycine-aspartic pentapeptide c(RGDyC) for targeted tumor accumulation. Results: 2D Nb2C MXenes were chosen based on their photothermal conversion capability (28.6%) in the near infrared (NIR)-II biowindow (1064 nm) for enhanced photothermal hyperthermia. Systematic in vitro and in vivo assessments demonstrate targeted and enhanced chemotherapy and photothermal hyperthermia of cancer (U87 cancer cell line and corresponding tumor xenograft; inhibition efficiency: 92.37%) in the NIR-II biowindow by these mesopore-coated 2D Nb2C MXenes. Conclusion: This work not only significantly broadens the biomedical applications of 2D Nb2C MXene for enhanced cancer therapy, but also provides an efficient strategy for surface engineering of 2D MXenes to satisfy versatile application requirements.
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Portadores de Fármacos/farmacocinética , Radiación Electromagnética , Glioblastoma/terapia , Hipertermia Inducida/métodos , Terapia Molecular Dirigida/métodos , Niobio/farmacocinética , Fototerapia/métodos , Animales , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/efectos de la radiación , Xenoinjertos , Ratones , Trasplante de Neoplasias , Neoplasias Experimentales/terapia , Niobio/efectos de la radiación , Propiedades de Superficie , Resultado del TratamientoRESUMEN
INTRODUCTION: Bladder cancer (BC) is a severe health burden: and has high recurrence and progression rates. Standard treatment starts with TURB followed by intravesical chemotherapy with Mitomycin C or immunotherapy with BCG. However, successful management still remains a challenge, because approximately 30% of patients have recurrence or progression within 5 years, and treatment has considerable side effects. Anticipating on the upcoming BCG shortage emphasizes, moreover, the necessity to develop and study novel treatments. This review explores emerging and novel salvage treatments as well as approaches of current treatments with decrease side-effects for non muscle-invasive bladder cancer (NMIBC). Areas covered: In this review, the authors provide an overview of the novel and emerging therapies for NMIBC. They also provide the currently available data and ongoing trials. Expert opinion: Key findings in the field of research on emerging intravesical drugs for the treatment of NMIBC are the promising results for device assisted treatments, treatment with intravesical immunotherapy, and treatments to expedite the immunotherapy checkpoint inhibitors. Other novel therapies are still in an experimental stage and have to make the transition towards the clinical setting to determine the benefit in terms of reduced side-effects, recurrence and progression rates.