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Na odontologia a decisão do tratamento é exclusiva dos cirurgiões dentistas e suas percepções, incluindo filosofia de tratamento, fazendo com que a prática de novos conceitos, tratamentos ou técnicas dependam não apenas de sua lógica ou eficácia biológica. Sendo assim, este estudo teve como objetivo avaliar os parâmetros envolvidos na tomada de decisão de cirurgiões dentistas clínicos e especialistas para a realização do tratamento endodôntico em sessão única ou múltiplas sessões. Para tanto, este estudo contou com uma coleta de dados através de um questionário online, aplicado cirurgiões dentistas clínicos gerais e especialistas em endodontia. As respostas foram tabuladas e analisadas por meio de estatística descritiva. Os resultados revelaram que a maioria dos endodontistas e dos clínicos gerais prefere realizar tratamento endodôntico em sessão única, devido ao menor desperdício de material, além do melhor domínio da anatomia e tratamento em um único momento. O motivo mais comum para os endodontistas e clínicos gerais escolherem o tratamento com múltiplas visitas é para dentes com prognóstico duvidoso e os casos em que o profissional aguarda a remissão dos sintomas antes da obturação. Em conclusão, a maioria dos endodontistas e dos clínicos gerais preferiu realizar tratamento endodôntico em sessão única.
In dentistry, treatment decisions are made exclusively by dental surgeons and their perceptions, including treatment philosophy, which means that the practice of new concepts, treatments or techniques depends not only on their logic or biological efficacy. Therefore, the aim of this study was to evaluate the parameters involved in clinical and specialist dental surgeons' decision to carry out endodontic treatment in single or multiple sessions. To this end, data was collected using an online questionnaire administered to general dental surgeons and endodontic specialists. The answers were tabulated and analyzed using descriptive statistics. The results revealed that the majority of endodontists and general practitioners prefer to carry out endodontic treatment in a single session, due to less wastage of material, as well as better mastery of the anatomy and treatment at a single time. The most common reason for endodontists and general practitioners to choose treatment with multiple visits is for teeth with a doubtful prognosis and cases in which the professional is waiting for symptoms to remit before filling. In conclusion, the majority of endodontists and general practitioners preferred to carry out endodontic treatment in a single session.
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Humanos , Masculino , Feminino , Tratamento do Canal Radicular , Protocolos Clínicos , Inquéritos e Questionários , Endodontia , Tomada de Decisão ClínicaRESUMO
Introdução: A parestesia é uma neuropatia que afeta a função sensorial. O Laser de Baixa Potência (LBP), por sua vez, apresenta propriedades analgésicas, bioestimuladoras e reparadoras. Objetivo: Realizar um levantamento na literatura científica sobre os aspectos gerais e benefícios do LBP no manejo terapêutico da parestesia, além de identificar a classificação e métodos de obtenção do diagnóstico desta condição. Materiais e Métodos: Tratou-se de uma revisão narrativa da literatura através da busca nas plataformas PubMed, SciELO, LILACS e Google Schoolar. Após o cruzamento dos descritores com os operadores booleanos e aplicação dos critérios de inclusão/exclusão, 26 estudos foram incluídos. Resultados: A parestesia pode ser classificada em neuropraxia, axonotmese e neurotmese, subdivididas em Grau I ao V. Seu diagnóstico pode ser executado através de testes subjetivos e objetivos. O LBP compreende em um dispositivo tecnológico com efeitos analgésico, anti-inflamatório e fotobiomodulador, que estimula o reparo neural. Os estudos mostram que a dosimetria nos comprimentos de onda vermelho e infravermelho, aplicação intra e extra oral, e com mais de uma sessão semanal exerce efeito modulatório positivo do reparo neural, com retorno progressivo da atividade sensitiva. Além disso, os estudos trazem uma ampla variação no número de pontos de aplicação, bem como no tempo de irradiação e quantidade de sessões, em virtude da extensão e tempo de diagnóstico da parestesia. Considerações finais: Apesar da alta complexidade da parestesia, o LBP exerce efeitos benéficos através do retorno da sensibilidade parcial ou total, além de ser um dispositivo bem tolerado pelo organismo e minimamente invasivo.
Introduction: Paresthesia is a neuropathy that affects sensory function. The Low-Level Laser (LLL), in turn, has analgesic, biostimulating and reparative properties. Purpose: Carry out a survey at the scientific literature on the general aspects and benefits of LLL in the therapeutic management of paresthesia in addition to identifying the classification and methods for obtaining a diagnosis of this condition. Materials and Methods: It was a narrative literature review through search in platforms PubMed, SciELO, LILACS and Google Schoolar. After crossing the descriptors with boolean operators and applying the inclusion/exclusion criteria, 26 articles were included in this study. Results: Paresthesia can be classified into neuropraxia, axonotmesis and neurotmesis, subdivided into Grades I to V. Its diagnostic can be carried out through subjective and objective tests. The LLL consists in a technological device with analgesic, anti-inflammatory and photobiomodulatory effects, which stimulates neural repair. Studies show that LLL in dosimetry at red and infrared wavelengths with intra and extra oral application and with more than one-week use exerts a positive modulatory effect on neural repair, with a progressive return of sensory activity. Furthermore, the studies show a wide variation in the number of application points, as well as the irradiation time and number of sessions, due to the extent and time of diagnosis of paresthesia. Final Considerations: Despite the high complexity of paresthesia, the LLL has beneficial effects through the return of partial or total sensitivity in addition being a device well tolerated by the body and minimally invasive.
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Parestesia/classificação , Parestesia/diagnóstico , Terapia com Luz de Baixa Intensidade , Terapia a LaserRESUMO
Background: Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. Methods: A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. Results: A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease. Conclusions: Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.
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We report a case of a man who was diagnosed with superficial hypopharyngeal cancer and recurrence of renal cell carcinoma in the duodenum, liver, and gluteus medius muscle simultaneously. He underwent endoscopic submucosal dissection for hypopharyngeal cancer in parallel with systemic immunotherapy for recurrent renal cell carcinoma, resulting in completely overcoming both malignancies. Endoscopic submucosal dissection is less invasive and can be performed in a shorter duration for treating superficial hypopharyngeal cancer compared with other treatment options, such as radiation therapy, chemotherapy, and surgery. Additionally, endoscopic submucosal carcinoma is adequately effective in controlling local lesions and has a satisfactorily good prognosis.
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Introduction: Cognitive rehabilitation is essential for schizophrenia treatment since it improves function. Moreover, the relationship between cognitive rehabilitation and functioning is significantly affected by negative symptoms and social cognition. Integrated Psychological Therapy (IPT) is a promising approach that integrates interventions in neurocognition, social cognition, and functional level. This study examines IPT's efficacy in chronic middle-aged inpatients. Methods: A randomized controlled study involved 44 individuals with schizophrenia. Twenty-one IPT participants received 50 biweekly sessions and medication, while twenty-three control participants received treatment as usual/supportive therapy and pharmacotherapy. Pre- and post-intervention and six- and twelve-month follow-ups were arranged to assess neurocognition, social perception, psychopathology, and functioning using the Matrics Consensus Cognitive Battery, Social Perception Scale, Positive and Negative Syndrome Scale, and Global Assessment of Functioning. Results: Speed of processing, attention/vigilance, overall composite, and neurocognitive composite scores improved significantly in the IPT group. Social Perception Scale performance improved in all areas after the intervention and persisted for 6 months. Positive, negative, and total psychopathology symptoms decreased significantly post-intervention and at the 12-month follow-up, whereas participants' functioning improved significantly. Conclusions: Middle-aged chronic inpatients with schizophrenia may benefit from IPT in neurocognition, social perception, psychopathology, and functioning. This field of study may provide insight into schizophrenia treatment, hence further research is encouraged.
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The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.
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Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (â¢OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.
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Clorofilídeos , Indóis , Platina , Polímeros , Porfirinas , Neoplasias da Glândula Tireoide , Microambiente Tumoral , Terapia por Ultrassom , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Humanos , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Indóis/química , Terapia por Ultrassom/métodos , Porfirinas/química , Porfirinas/farmacologia , Polímeros/química , Animais , Platina/química , Platina/uso terapêutico , Platina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Apoptose/efeitos dos fármacos , Nanopartículas/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Quinolinas/farmacologia , Quinolinas/química , Camundongos Nus , Portadores de Fármacos/químicaRESUMO
Numerous nanoparticles have been utilized to deliver Fe2+ for tumor ferroptosis therapy, which can be readily converted to Fe3+via Fenton reactions to generate hydroxyl radical (â¢OH). However, the ferroptosis therapeutic efficacy of large tumors is limited due to the slow conversion of Fe3+ to Fe2+via Fenton reactions. Herein, a strategy of intratumor Fe3+/2+ cyclic catalysis is proposed for ferroptosis therapy of large tumors, which was realized based on our newly developed hollow mesoporous iron sesquioxide nanoparticle (HMISN). Cisplatin (CDDP) and Gd-poly(acrylic acid) macrochelates (GP) were loaded into the hollow core of HMISN, whose surface was modified by laccase (LAC). Fe3+, CDDP, GP, and LAC can be gradually released from CDDP@GP@HMISN@LAC in the acidic tumor microenvironment. The intratumor O2 can be catalyzed into superoxide anion (O2â¢-) by LAC, and the intratumor NADPH oxidases can be activated by CDDP to generate O2â¢-. The O2â¢- can react with Fe3+ to generate Fe2+, and raise H2O2 level via the superoxide dismutase. The generated Fe2+ and H2O2 can be fast converted into Fe3+ and â¢OH via Fenton reactions. The cyclic catalysis of intratumor Fe3+/2+ initiated by CDDP@GP@HMISN@LAC can be used for ferroptosis therapy of large tumors.
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Ferroptose , Ferro , Ferroptose/efeitos dos fármacos , Animais , Catálise , Humanos , Ferro/química , Linhagem Celular Tumoral , Nanopartículas/química , Porosidade , Camundongos , Cisplatino/química , Cisplatino/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Peróxido de Hidrogênio/química , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , FemininoRESUMO
Ferroptosis is an iron-dependent form of programmed cell death with the potential to reverse traditional cancer therapy resistance. The combination of ferroptosis with chemotherapy, photodynamic therapy and X-ray therapy has demonstrated remarkably improved therapeutic efficiency. Radiopharmaceutical therapy (RPT) is an emerging approach that achieves precise radiation to diseased tissues via radionuclide delivery. However, insufficient accumulation and retention of therapeutic radiopharmaceuticals in tumor region as well as cancer radioresistance impact treatment efficacy. Here, a nanoassembly of renal clearable ultrasmall iron nanoparticles (USINPs) and 131I-aPD-L1 is prepared via the affinity of fluorophenylboronic acid modified on the USINPs with 131I-aPD-L1. The 150 nm USINAs(131I-aPD-L1) nanoassembly is stable in blood circulation, effectively targets to the tumor and disassembles in the presence of ATP in the tumor microenvironment. Both in vitro and in vivo experiments prove that USINPs-induced ferroptosis boosted the tumor radiosensitization to 131I while 131I-mediated RPT further enhanced ferroptosis. Meanwhile, the immunogenic cell death caused by RPT and ferroptosis combined with PD-L1 immune checkpoint blockade therapy exhibits a strong antitumor immunity. This study provides a novel way to improve the tumor accumulation of ferroptosis inducer and radiopharmaceuticals, insights into the interaction between RPT and ferroptosis and an effective SPECT-guided ferroptosis-enhanced radio-immunotherapy.
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Ferroptose , Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Ferroptose/efeitos dos fármacos , Animais , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Camundongos , Radioisótopos do Iodo/uso terapêutico , Radioisótopos do Iodo/química , Linhagem Celular Tumoral , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Ferro/química , Camundongos Endogâmicos BALB C , Imunoterapia/métodos , Radioimunoterapia/métodos , Feminino , Neoplasias/terapiaRESUMO
Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.
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Terapia por Ultrassom , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Terapia por Ultrassom/métodos , Ratos Sprague-Dawley , Ratos , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/química , Camundongos , Estimulação Elétrica , Masculino , Infecções Estafilocócicas/terapia , Poliésteres/química , Espécies Reativas de Oxigênio/metabolismo , Terapia por Estimulação Elétrica/métodos , Neovascularização Fisiológica/efeitos dos fármacosRESUMO
Chemoimmunotherapy is an emerging paradigm in the clinic for treating several malignant diseases, such as non-small cell lung cancer, breast cancer, and large B-cell lymphoma. However, the efficacy of this strategy is still restricted by serious adverse events and a high therapeutic termination rate, presumably due to the lack of tumor-targeted distribution of both chemotherapeutic and immunotherapeutic agents. Targeted drug delivery has the potential to address this issue. Among the most promising nanocarriers in clinical translation, liposomes have drawn great attention in cancer chemoimmunotherapy in recent years. Liposomes-enabled cancer chemoimmunotherapy has made significant progress in clinics, with impressive therapeutic outcomes. This review summarizes the latest preclinical and clinical progress in liposome-enabled cancer chemoimmunotherapy and discusses the challenges and future directions of this field.
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Imunoterapia , Lipossomos , Neoplasias , Lipossomos/química , Humanos , Imunoterapia/métodos , Animais , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagemRESUMO
Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.
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Antibacterianos , Alicerces Teciduais , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Animais , Alicerces Teciduais/química , Camundongos , Cicatrização/efeitos dos fármacos , Raios Infravermelhos , Terapia Fototérmica , Engenharia Tecidual/métodos , Taninos/química , Taninos/farmacologia , Materiais Inteligentes/química , Staphylococcus aureus/efeitos dos fármacos , Masculino , Polietilenoglicóis/químicaRESUMO
Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.
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Antibacterianos , Biofilmes , Gálio , Espécies Reativas de Oxigênio , Biofilmes/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Gálio/química , Gálio/farmacologia , Camundongos , Portadores de Fármacos/química , Células RAW 264.7 , Humanos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
Multiple Sclerosis (MS) is an autoimmune condition targeting the central nervous system (CNS) characterized by focal demyelination with inflammation, causing neurodegeneration and gliosis. This is accompanied by a refractory period in relapsing MS or chronic progression in primary progressive MS. Current MS treatments target disease relapses and aim to reduce further demyelination and disability. These include the treatment of acute exacerbations through global immunomodulation upon corticosteroid administration, which are accompanied by adverse reactions. Disease modifying therapies (DMTs) which provide targeted immunosuppression of T and B cells, and sequestration of leukocytes out of CNS, have led to further improvements in demyelination prevention and disease burden reduction. Despite their efficacy, DMTs are ineffective in remyelination, pathology reversal and have minimal effects in progressive MS. The advent of modern biomedical engineering approaches in combination with a better understanding of MS pathology, has led to the development of novel, regenerative approaches to treatment. Such treatments utilize neural stem cells (NSCs) and can reduce disease relapses and reverse damage caused by the disease through localized tissue regeneration. While at initial stages, pre-clinical and clinical studies utilizing NSCs and immune modulation have shown promising outcomes in tissue regeneration, creating a potential new era in MS therapy.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Animais , Engenharia Biomédica/métodos , Células-Tronco Neurais/transplanteRESUMO
Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.
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Nanopartículas , Dióxido de Silício , Humanos , Animais , Raios X , Nanopartículas/química , Feminino , Dióxido de Silício/química , Camundongos , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Células HeLa , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
Copper (Cu), an essential micronutrient with redox properties, plays a pivotal role in a wide array of pathological and physiological processes across virtually all cell types. Maintaining an optimal copper concentration is critical for cellular survival: insufficient copper levels disrupt respiration and metabolism, while excess copper compromises cell viability, potentially leading to cell death. Similarly, in the context of cancer, copper exhibits a dual role: appropriate amount of copper can promote tumor progression and be an accomplice, yet beyond befitting level, copper can bring about multiple types of cell death, including autophagy, apoptosis, ferroptosis, immunogenic cell death, pyroptosis, and cuproptosis. These forms of cell death are beneficial against cancer progression; however, achieving precise copper regulation within tumors remains a significant challenge in the pursuit of effective cancer therapies. The emergence of nanodrug delivery systems, distinguished by their precise targeting, controlled release, high payload capacity, and the ability to co-deliver multiple agents, has revitalized interest in exploiting copper's precise regulatory capabilities. Nevertheless, there remains a dearth of comprehensive review of copper's bidirectional effects on tumorigenesis and the role of copper-based nanomaterials in modulating tumor progression. This paper aims to address this gap by elucidating the complex role in cancer biology and highlighting its potential as a therapeutic target. Through an exploration of copper's dualistic nature and the application of nanotechnology, this review seeks to offer novel insights and guide future research in advancing cancer treatment.
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Cobre , Nanoestruturas , Neoplasias , Cobre/química , Humanos , Animais , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Morte Celular/efeitos dos fármacosRESUMO
Purpose: To evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP). Design: Phase I prospective, open-label, single-center study. Participants: Seven eyes (7 patients) with RP with best-corrected visual acuity (BCVA) of 20/60 to 20/400 or visual field constriction to within 10°. Methods: A comprehensive examination with ETDRS BCVA, macular OCT, perimetry, and fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under good manufacturing practice conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACS system. Isolated CD34+ cells were released for clinical use if viability, sterility, and purity met the release criteria accepted by the United States Food and Drug Administration for this clinical study. Main Outcome Measures: Number of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry. Results: All isolated CD34+ cells passed the release criteria. A mean of 3.26 ± 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for 1 participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. Best-corrected visual acuity remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except 1 eye with transient improvement at 1 month and worsening of both eyes at 6 months. Conclusions: Intravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMO
Short- and medium-chain fatty acids (SMCFA) are monocarboxylic acids with a carbon chain length of 1-12 carbon atoms. They are mainly produced in humans by the gut microbiota, play crucial metabolic roles, are vital for intestinal health, and have multifaceted impact on immune and neurological functions. Accurate detection and quantification of SMCFA in different human biofluids is achieved using 3-nitro phenylhydrazine (3-NPH) derivatization of the free fatty acids followed by reverse phase liquid chromatography (RPLC) separation and detection by tandem mass spectrometry (MS/MS). Here, we describe the simultaneous measurement of 14 SMCFA and lactate in detail. All 3-NPH-SMCFA-hydrazones are separated in less than 5 min with an 8-min total run time (injection-to-injection). Linear dynamic range over 0.1-500 µM is achieved for most SCFAs, while it is 0.05-100 µM for MCFAs. Validation of the procedure depicts good linearity (R2 > 0.98) and repeatability (CV ≤ 20%). The lower limit of detection (LLOD) is 10-30 nM. The lower limit of quantification (LLOQ) is 50-100 nM for most analytes, while it is 0.5 µM for acetate. In conclusion, the method offers several benefits compared to alternative methods regarding throughput, selectivity, sensitivity, and robustness.
Assuntos
Cromatografia de Fase Reversa , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Humanos , Cromatografia de Fase Reversa/métodos , Ácidos Graxos Voláteis/análise , Ensaios de Triagem em Larga Escala/métodos , Limite de Detecção , Ácidos Graxos/análise , Ácidos Graxos/química , Reprodutibilidade dos TestesRESUMO
Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.
Assuntos
Antioxidantes , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistência à Insulina , Células Secretoras de Insulina , Nanopartículas , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Antioxidantes/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Nanopartículas/química , Camundongos , Masculino , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos Endogâmicos C57BL , Zingiber officinale/química , Dióxido de Silício/química , Exossomos/metabolismo , Biomimética/métodos , Estresse Oxidativo/efeitos dos fármacosRESUMO
The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.