RESUMO
Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.
Assuntos
Isquemia , Espermatozoides , Trombose , Animais , Masculino , Camundongos , Isquemia/terapia , Espermatozoides/efeitos dos fármacos , Trombose/tratamento farmacológico , Terapia Trombolítica/métodos , Hipertermia Induzida/métodos , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Fibrinolíticos/química , Humanos , Camundongos Endogâmicos C57BLRESUMO
The prospective of percutaneous drug delivery (PDD) mechanisms to address the limitations of oral and injectable treatment for rheumatoid arthritis (RA) is increasing. These limitations encompass inadequate compliance among patients and acute gastrointestinal side effects. However, the skin's intrinsic layer can frequently hinder the percutaneous dispersion of RA medications, thus mitigating the efficiency of drug delivery. To circumvent this constraint, we developed a strontium ranelate (SrR)-loaded alginate (ALG) phototherapeutic hydrogel to assess its effectiveness in combating RA. Our studies revealed that this SrR-loaded ALG hydrogel incorporating photoelectrically responsive molybdenum disulfide nanoflowers (MoS2 NFs) and photothermally responsive polypyrrole nanoparticles (Ppy NPs) to form ALG@SrR-MoS2 NFs-Ppy NPs demonstrated substantial mechanical strength, potentially enabling delivery of hydrophilic therapeutic agents into the skin and significantly impeding the progression of RA. Comprehensive biochemical, histological, behavioral, and radiographic analyses in an animal model of zymosan-induced RA demonstrated that the application of these phototherapeutic ALG@SrR-MoS2 NFs-Ppy NPs effectively reduced inflammation, increased the presence of heat shock proteins, regulatory cluster of differentiation M2 macrophages, and alleviated joint degeneration associated with RA. As demonstrated by our findings, treating RA and possibly other autoimmune disorders with this phototherapeutic hydrogel system offers a distinctive, highly compliant, and therapeutically efficient method.
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Artrite Reumatoide , Nanogéis , Animais , Artrite Reumatoide/tratamento farmacológico , Nanogéis/química , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Alginatos/química , Polissacarídeos/química , Dissulfetos/química , Molibdênio/química , Hidrogéis/química , Nanopartículas/química , Administração Cutânea , MasculinoRESUMO
Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.
Assuntos
Nanopartículas , Trombose , Dipiridamol/farmacologia , Nanopartículas/uso terapêutico , Selectina-P , Fototerapia/métodos , Polímeros , Pirróis , Trombose/tratamento farmacológico , AnimaisRESUMO
Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.
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Antifibrinolíticos , Artroplastia do Joelho , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/farmacologia , Ácido Tranexâmico/uso terapêutico , Adesivo Tecidual de Fibrina/farmacologia , Adesivo Tecidual de Fibrina/uso terapêutico , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Estudos Prospectivos , Perda Sanguínea Cirúrgica/prevenção & controleRESUMO
Rapid, accessible, and highly accurate biosensors for the detection of addictive and abused drugs are needed to reduce the adverse personal and societal impacts of addiction. Modern sensors that utilize next-generation technologies, e.g., nanobiotechnology and nanoarchitectonics, have triggered revolutionary progress in the field as they allow accurate detection and tracking of trace levels of major classes of drugs. This paper reviews advances in the field of biosensors for the detection of commonly abused drugs, both prescribed such as codeine and morphine, and illegal narcotics like cocaine.
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Técnicas Biossensoriais , Cocaína , Drogas Ilícitas , MorfinaRESUMO
BACKGROUND: To assess clinical and functional outcomes of patients aged 40 years or older receiving PCL reconstruction surgery. METHODS: All patients older than 40 years with isolated PCL rupture who underwent PCL reconstruction surgery were enrolled into the retrospective study. Associated meniscal injuries, osteochondral lesions, postoperative complications, and the rate of return to the preinjury level of activity were extracted. Outcomes included International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and Tegner activity score. The minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were used to evaluate the clinically relevant value of PCL reconstruction in this population. RESULTS: In total, 41 patients with a mean age of 51.7 years were included. The mean follow-up time was 32.8 months. Associated lesions included meniscal injuries (48.8%) and osteochondral lesions (97.6%). Improvement in the IKDC score (from 46.5 preoperatively to 79.0 postoperatively, p < 0.0001), Lysholm score (from 65.5 to 88.3, p < 0.0001), and Tegner activity score (from 2.3 to 4.0, p < 0.0001) was recorded. The clinically relevant value based on the MCID showed that 34 of 41 patients (82.9%) had a ΔIKDC score exceeding 16.8; all patients (100%) showed a ΔLysholm score exceeding 8.9; and 35 of 41 patients (85.4%) showed a ΔTegner activity score exceeding 0.5. Regarding the PASS, none of the patients had an IKDC score exceeding 75.9 preoperatively, whereas 27 of 41 patients (65.9%) had a score of more than 75.9 postoperatively. All patient had ≥ grade II knee instability preoperatively. Postoperatively, 36 patients (87.8%) had no significant joint translation, and 5 patients (12.2%) had grade I instability. Twenty-one patients (51.2%) returned to their preinjury level of activity. Five patients (12.2%) developed Ahlbäck grade I radiographic osteoarthritis. No rerupture or other major perioperative complications were reported. CONCLUSIONS: PCL reconstruction is a reliable surgery for middle-aged patients suffering from persistent instability even after failed conservative treatment, with significant improvement in patient-reported outcomes that exceeded MCID in the majority of patients, restoration of subjective instability, and approximately half of the patients returned to preinjury activity levels. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Instabilidade Articular , Reconstrução do Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Adulto , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Seguimentos , Humanos , Instabilidade Articular/cirurgia , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Ligamento Cruzado Posterior/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Metal-organic frameworks (MOFs) nanoparticles are a class of porous crystalline materials constructed from the bonding metal ions or clusters linked with organic ligands to form frameworks. MIL-101(Cr), one of the most representative MOFs, is a three-dimensional chromium terephthalate-base porous material consisted of chromium (III)-trimers cross-linked by 1,4-benzene dicarboxylate. The present study focused on determining the safety of MIL-101(Cr) nanoparticle. The acute oral toxicity and 28-day oral toxicity in mice were investigated. An acute oral toxicity test of MIL-101(Cr) nanoparticle for female mice showed that no mortality or any significant change observed at 2000â¯mg/kg body weight. A dose-dependent 28-day oral toxicity evaluation of MIL-101(Cr) nanoparticle for male and female mice revealed no significant effects on mortality, feed consumption, body weight, organ weight, and behavior. Assessments of hematology, clinical biochemistry, and histopathology revealed no adverse effects in mice treated with MIL-101(Cr) nanoparticle (10-1000â¯mg/kg). These results suggest that MIL-101(Cr) nanoparticle has no significant acute and subacute toxicity. The no observed adverse effect level of MIL-101(Cr) nanoparticle was defined as at least 1000â¯mg/kg/day orally for 28 days for male and female mice.
Assuntos
Cromo/toxicidade , Estruturas Metalorgânicas/toxicidade , Nanopartículas/toxicidade , Animais , Feminino , Masculino , Camundongos Endogâmicos ICR , Nível de Efeito Adverso não Observado , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
Pectin, a major component of the primary cell wall, is synthesized in the Golgi apparatus and exported to the cell wall in a highly methylesterified form, then is partially demethylesterified by pectin methylesterases (PMEs; EC 3.1.1.11). PME activity on the status of pectin methylesterification profoundly affects the properties of pectin and, thereby, is critical for plant development and the plant defense response, although the roles of PMEs under heat stress (HS) are poorly understood. Functional genome annotation predicts that at least 66 potential PME genes are contained in Arabidopsis (Arabidopsis thaliana). Thermotolerance assays of PME gene T-DNA insertion lines revealed two null mutant alleles of PME34 (At3g49220) that both consistently showed reduced thermotolerance. Nevertheless, their impairment was independently associated with the expression of HS-responsive genes. It was also observed that PME34 transcription was induced by abscisic acid and highly expressed in guard cells. We showed that the PME34 mutation has a defect in the control of stomatal movement and greatly altered PME and polygalacturonase (EC 3.2.1.15) activity, resulting in a heat-sensitive phenotype. PME34 has a role in the regulation of transpiration through the control of the stomatal aperture due to its cell wall-modifying enzyme activity during the HS response. Hence, PME34 is required for regulating guard cell wall flexibility to mediate the heat response in Arabidopsis.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Hidrolases de Éster Carboxílico/metabolismo , Resposta ao Choque Térmico/fisiologia , Estômatos de Plantas/fisiologia , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Hidrolases de Éster Carboxílico/genética , Membrana Celular/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Mutação , Transpiração Vegetal/fisiologia , Plantas Geneticamente ModificadasRESUMO
BACKGROUND: The occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)-α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population. MATERIAL AND METHODS: In total, 278 patients with Graves' disease (GD) and 55 patients with Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing were used for genotyping. RESULTS: Significantly lower frequencies of the GA genotype and A allele of rs17445836 were found in the HT group than in the control group (P = 0·028, odds ratio (OR) = 4·71 and P = 0·022, OR = 4·40, respectively). Both rs17445836 and rs2280381 were associated with the presence of an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was associated with the level of AmiA in AITD. CONCLUSIONS: rs17445836 of IRF8 is a possible genetic variant associated with the development of HT. rs17445836 was associated with the production of thyroid antibody, and the GG genotype of rs17445836 was associated with a higher AmiA titre than the GA genotype.
Assuntos
Doença de Graves/genética , Doença de Hashimoto/genética , Fatores Reguladores de Interferon/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Povo Asiático/genética , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Microssomos/imunologia , Prevalência , TaiwanRESUMO
BACKGROUND: Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progression. As such, targeting the EMT represents an important therapeutic strategy for preventing or treating prostate cancer metastasis. Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanism by which berberine represses the metastatic potential of prostate cancer. METHODS: The effects of berberine on cell migration and invasion were determined by transwell migration assay and Matrigel invasion assay. Expressions of EMT-related genes were determined by an EMT PCR Array and a quantitative RT-PCR. The prognostic relevance of berberine's modulation of EMT-related genes in prostate cancer was evaluated using Kaplan-Meier survival analysis. RESULTS: Berberine exerted inhibitory effects on the migratory and invasive abilities of highly metastatic prostate cancer cells. These inhibitory effects of berberine resulted in significant repression of a panel of mesenchymal genes that regulate the developmental EMT. Among EMT-related genes downregulated by berberine, high BMP7, NODAL and Snail gene expressions of metastatic prostate cancer tissues were associated with shorter survival of prostate cancer patients and provide potential therapeutic interventions. CONCLUSIONS: We concluded that berberine should be developed as a pharmacological agent for use in combination with other anticancer drug for treating metastatic prostate cancer.
Assuntos
Berberina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Berberina/administração & dosagem , Biomarcadores Tumorais/genética , Proteína Morfogenética Óssea 7/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteína Nodal/genética , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Proteínas Wnt/genéticaRESUMO
Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Mapas de Interação de Proteínas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Células HEK293 , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transdução de Sinais , Análise Serial de Tecidos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
BACKGROUND: The most common cause of facial palsy is idiopathic or Bell's palsy. Although uncommon in the postantibiotic era, otomastoiditis should receive more attention as a cause of facial palsy, especially in young children. Delay of identification and treatment may result in permanent neurological sequelae. OBJECTIVES: To describe a 3-month-old infant eventually diagnosed with masked otomastoiditis with initial presentation of facial palsy. CASE REPORT: We report a case of facial palsy complicated by masked otomastoiditis in a 3-month-old male infant. The facial palsy completely recovered after parenteral antibiotics and myringotomy. CONCLUSION: We use this case to emphasize that otomastoiditis should be considered in the differential diagnosis of young children with facial palsy. Diagnosis may be difficult as signs and symptoms of otitis media in young children are often nonspecific and subtle, particularly in infants. Early diagnosis and careful investigation of middle ear regions should be performed to avoid permanent sequelae.
Assuntos
Paralisia Facial/etiologia , Otite Média/complicações , Doença Aguda , Humanos , Lactente , Masculino , Mastoidite/complicaçõesRESUMO
Thrombotic blockages within blood vessels give rise to critical cardiovascular disorders, including ischemic stroke, venous thromboembolism, and myocardial infarction. The current approach to the therapy of thrombolysis involves administering Plasminogen Activators (PA), but it is hindered by fast drug elimination, narrow treatment window, and the potential for bleeding complications. Leveraging nanomedicine to encapsulate and deliver PA offers a solution by improving the efficacy of therapy, safeguarding the medicine from proteinase biodegradation, and reducing unwanted effects in in vivo trials. In this review, we delve into the underlying venous as well as arterial thrombus pathophysiology and provide an overview of clinically approved PA used to address acute thrombotic conditions. We explore the existing challenges and potential directions within recent pivotal research on a variety of targeted nanocarriers, such as lipid, polymeric, inorganic, and biological carriers, designed for precise delivery of PA to specific sites. We also discuss the promising role of microbubbles and ultrasound-assisted Sono thrombolysis, which have exhibited enhanced thrombolysis in clinical studies. Furthermore, our review delves into approaches for the strategic development of nano-based carriers tailored for targeting thrombolytic action and efficient encapsulation of PA, considering the intricate interaction in biology systems as well as nanomaterials. In conclusion, the field of nanomedicine offers a valuable method for the exact and effective therapy of severe thrombus conditions, presenting a pathway toward improved patient outcomes and reduced complications.
Assuntos
Fibrinolíticos , Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Terapia Trombolítica/tendências , Animais , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Nanomedicina/métodos , Nanomedicina/tendências , Trombose/tratamento farmacológico , Ativadores de Plasminogênio/administração & dosagem , Ativadores de Plasminogênio/uso terapêutico , Nanopartículas/química , Nanopartículas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendênciasRESUMO
The management of diabetic kidney disease (DKD) faces challenges stemming from intricate pathologies and suboptimal biodistributions during drug delivery. Although clinically available anti-inflammatory agents hold considerable promise for treating DKD, their therapeutic effectiveness is limited when utilized in isolation. To address this limitation, we introduced a novel self-oriented nanocarrier termed F-GCS@Hb-DIF, designed to synergistically integrate the therapeutic diferuloylmethane (DIF), the polysaccharide fucoidan/glycol chitosan (F-GCS), and phototherapeutic hemoglobin (Hb). F-GCS@Hb-DIF demonstrated the capability to autonomously navigate toward diseased renal sites and directly release drugs into the cytoplasm of target cells following intranasal administration. This self-directed drug delivery system increased the accumulation of Hb and DIF at the target site as per biodistribution data. This enhancement allowed F-GCS@Hb-DIF to adopt a synergistic approach in treating the complex pathologies of DKD during the two-week treatment period. This approach entails modulating immunity, promoting renal functional recovery with a tissue-protective effect, and alleviating renal inflammation. These results underscore the promising therapeutic potential of F-GCS@Hb-DIF in managing DKD and other degenerative diseases associated with diabetes.
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X-ray Photodynamic Therapy (XPDT) is an emerging, deeply penetrating, and non-invasive tumor treatment that stimulates robust antitumor immune responses. However, its efficacy is often limited by low therapeutic delivery and immunosuppressant within the tumor microenvironment. This challenge can potentially be addressed by utilizing X-ray responsive iron-glycol chitosan-polypyrrole nanozymes (GCS-I-PPy NZs), which activate M1 macrophages. These nanozymes increase tumor infiltration and enhance the macrophages' intrinsic immune response and their ability to stimulate adaptive immunity. Authors have designed biocompatible, photosensitizer-containing GCS-I-PPy NZs using oxidation/reduction reactions. These nanozymes were internalized by M1 macrophages to form RAW-GCS-I-PPy NZs. Authors' results demonstrated that these engineered macrophages effectively delivered the nanozymes with potentially high tumor accumulation. Within the tumor microenvironment, the accumulated GCS-I-PPy NZs underwent X-ray irradiation, generating reactive oxygen species (ROS). This ROS augmentation significantly enhanced the therapeutic effect of XPDT and synergistically promoted T cell infiltration into the tumor. These findings suggest that nano-engineered M1 macrophages can effectively boost the immune effects of XPDT, providing a promising strategy for enhancing cancer immunotherapy. The ability of GCS-I-PPy NZs to mediate M1 macrophage activation and increase tumor infiltration highlights their potential in overcoming the limitations of current XPDT approaches and improving therapeutic outcomes in melanoma and other cancers.
Assuntos
Quitosana , Macrófagos , Fotoquimioterapia , Polímeros , Pirróis , Neoplasias da Bexiga Urinária , Quitosana/química , Fotoquimioterapia/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Animais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Camundongos , Polímeros/química , Pirróis/química , Pirróis/farmacologia , Raios X , Ferro/química , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Células RAW 264.7 , Linhagem Celular Tumoral , Humanos , Nanopartículas/químicaRESUMO
The process of wound healing is a complex, multi-phase phenomenon crucial for optimal tissue regeneration. Traditional drug delivery systems often target specific phases of wound repair, neglecting the dynamic interplay among the stages. This limitation highlights the need for comprehensive delivery systems that cater to the holistic needs of wound healing, enhancing tissue regeneration efficiency. Herein, we explored the utility of platelet-derived extracellular vesicles (pEVs) as carriers for the phototherapeutic diferuloylmethane (DIF), resulting in a formulation termed DIF@pEVs, which is designed to sequentially address the distinct phases of wound healing. Initially, upon exposure to light, administered DIF@pEVs generate photodynamic therapy-derived reactive oxygen species during the early inflammatory phase. This generation of ROS aims to modulate the inflammatory response, induce the protective mechanisms of heat shock proteins, and kickstart the tissue regeneration process. Following this initial phase, the remaining DIF and pEVs persist in promoting tissue repair and regeneration. Ultimately, it reduces inflammation, speeds up the healing process, and promotes vascular and follicular formation in a model of burn wound skin damage, thereby supporting skin regeneration. The deployment of DIF@pEVs represents an advancement in regenerative medicine, providing a precise, versatile approach to fostering regeneration across a wide range of clinical scenarios.
Assuntos
Plaquetas , Queimaduras , Vesículas Extracelulares , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Queimaduras/patologia , Queimaduras/metabolismo , Animais , Plaquetas/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia , Humanos , Pele/patologia , Masculino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Thrombosis presents a critical health threat globally, with high mortality and incidence rates. Clinical treatment faces challenges such as low thrombolytic agent bioavailability, thrombosis recurrence, ischemic hypoxia damage, and neural degeneration. This study developed biocompatible Chlamydomonas Reinhardtii micromotors (CHL) with photo/magnetic capabilities to address these needs. These CHL micromotors, equipped with phototaxis and photosynthesis abilities, offer promising solutions. A core aspect of this innovation involves incorporating polysaccharides (glycol chitosan (GCS) and fucoidan (F)) into ferric Metal-organic frameworks (MOFs), loaded with urokinase (UK), and subsequently self-assembled onto the multimodal CHL, forming a core-shell microstructure (CHL@GCS/F-UK-MOF). Under light-navigation, CHL@GCS/F-UK-MOF is shown to penetrate thrombi, enhancing thrombolytic biodistribution. Combining CHL@GCS/F-UK-MOF with the magnetic hyperthermia technique achieves stimuli-responsive multiple-release, accelerating thrombolysis and rapidly restoring blocked blood vessels. Moreover, this approach attenuates thrombi-induced ischemic hypoxia disorder and tissue damage. The photosynthetic and magnetotherapeutic properties of CHL@GCS/F-UK-MOF, along with their protective effects, including reduced apoptosis, enhanced behavioral function, induced Heat Shock Protein (HSP), polarized M2 macrophages, and mitigated hypoxia, are confirmed through biochemical, microscopic, and behavioral assessments. This multifunctional biomimetic platform, integrating photo-magnetic techniques, offers a comprehensive approach to cardiovascular management, advancing related technologies.
RESUMO
Combination therapy based on precise phototherapies combined with immune modulation provides successful antitumor effects. In this study, a combination therapy is designed based on phototactic, photosynthetic, and phototherapeutic Chlamydomonas Reinhardtii (CHL)-glycol chitosan (GCS)-polypyrrole (PPy) nanoparticle (NP)-enhanced immunity combined with the tumor microenvironment turnover of cytotoxic T cells and M1/M2 macrophages, which is based on photothermal GCS-PPy NPs decorated onto the phototactic and photosynthetic CHL. Phototherapy based on CHL-GCS-PPy NPs alleviates hypoxia and modulates the tumor immune microenvironment, which induces tumor cell death. In particular, the precise antitumor immune response and potent immune memory induced by combining self-navigated phototherapies significantly alleviate the progression of bladder cancer in C57BL/6 mice and effectively inhibit bladder tumor growth. Furthermore, they also potentially prevent tumor recurrence, which provides a promising therapeutic strategy for clinical tumor therapy.
RESUMO
BACKGROUND: The Taiwan CDC provided free oseltamivir to all patients with influenza infections confirmed by rapid testing or who had clinical warning symptoms during the 2009 H1N1 influenza pandemic in Taiwan. However, oseltamivir utilization patterns, cost, and outcomes among oseltamivir-treated patients remained unclear. METHOD: A population-level, observational cohort study was conducted using the Taiwan National Health Insurance Database from January to December 2009 to describe the use of oseltamivir. RESULT: Prescription trend over weeks increased after a change in government policy and responded to the influenza virus activity. The overall prescription rate was 22.33 per 1000 persons, with the highest prescription rate of 116.5 for those aged 7-12 years, followed by 69.0 for those aged 13-18 years, while the lowest rate was 1.7 for those aged ≥ 65 years. As influenza virus activity increased, the number of prescriptions for those aged ≤18 years rose significantly, whereas no substantial change was observed for those aged ≥65 years. There were also regional variations in terms of oseltamivir utilization and influenza complication rates. CONCLUSIONS: Oseltamivir was widely used in the 2009 H1N1 influenza pandemic in Taiwan, particularly in those aged 7-18 years. The number of prescriptions for oseltamivir increased with a change in government policy and with increasing cases of pandemic influenza. Further study is needed to examine whether there is an over- or under-use of anti-influenza drugs in different age groups or regions and to examine the current policy of public use of anti-influenza drugs to reduce influenza-associated morbidity and mortality.
Assuntos
Antivirais/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/economia , Criança , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Oseltamivir/economia , Taiwan/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.