Rol comunicativo del cuidador en pacientes con accidente cerebrovascular, Sincelejo, Colombia / The communicative role of caregivers assisting stroke patients from Sincelejo, Colombia / Papel comunicativo do cuidador em pacientes com acidente vascular cerebral, Sincelejo, Colômbia

Introducción: Las enfermedades cerebrovasculares son consideradas un problema de salud pública que afectan muchas capacidades en el individuo, entre ellas la comunicación; de esta manera el cuidador cumple un papel fundamental en su recuperación. Objetivo: Describir el rol comunicativo del cuidador en la atención a pacientes con secuelas de accidente cerebrovascular en la ciudad de Sincelejo, Colombia. Materiales y métodos: Paradigma positivista, enfoque cuantitativo y estudio descriptivo de corte transversal realizado con 40 cuidadores, seleccionados según muestreo por criterios y reclutamiento en cadena. Se utilizó una encuesta sociodemográfica, una sobre favorecimiento y bienestar comunicativo y Escala Likert, se realizó análisis de fiabilidad y consistencia interna del instrumento. Resultados: Predominaron cuidadores de sexo femenino, sobresale el cuidador informal, con estudios de secundaria y estrato socioeconómico bajo. Se encontró una actitud favorable en la competencia del ser y saber hacer, prima el buen trato, justicia y respeto. La competencia del saber evidenció actitud desfavorable, caracterizada por un conocimiento limitado frente a la patología, insuficientes destrezas, técnicas y habilidades para cumplir sus funciones y estrategias empleadas. Conclusión: Es necesario cualificar al cuidador en la atención del paciente con accidente cerebrovascular, mediante programas de que dinamicen la competencia del ser, saber y saber hacer

Introduction: Cerebrovascular diseases are a public health problem affecting the different capabilities of patients, including communication. Thus, caregivers play a fundamental role in their recovery. Objective: To describe the communicative role of caregivers in the support of patients with stroke sequelae in the city of Sincelejo, Colombia. Materials and methods: A positivist paradigm, quantitative approach, and descriptive cross-sectional study was carried out with 40 caregivers, who were selected according to criteria sampling and chain recruitment. A sociodemographic survey about favorability and communicative well-being as well as the Likert Scale were applied. A reliability and internal consistency analysis was conducted. Results: The majority of caregivers were women. Informal caregivers, with high school education, and belonging to low socioeconomic status were also predominant. A positive attitude regarding competences such as being and knowing what to do; appropriate treatment of patients, with justice and respect, were observed as common features. The knowledge competence was considered unfavorable, which was characterized by limited understanding regarding pathology, strategies used, and insufficient skills, techniques, and abilities to fulfill their functions. Conclusions: Caregivers of stroke patients should be qualified through programs that improve the being, knowing, and knowing how to do competencies.

Introdução: As doenças cerebrovasculares são consideradas um problema de saúde pública que afeta diversas capacidades do indivíduo, incluindo a comunicação; desta forma, o cuidador desempenha um papel fundamental na sua recuperação. Objetivo: Descrever o papel comunicativo do cuidador no cuidado de pacientes com sequelas de acidente vascular cerebral na cidade de Sincelejo, Colômbia. Materiais e métodos: Paradigma positivista, abordagem quantitativa e estudo transversal descritivo realizado com 40 cuidadores, selecionados segundo critérios de amostragem e recrutamento em cadeia. Foi utilizado um inquérito sociodemográfico, um de favorabilidade e bem-estar comunicativo e uma Escala Likert, foi realizada uma análise da fiabilidade e consistência interna do instrumento. Resultados: Predominaram cuidadores do sexo feminino, destacando-se os cuidadores informais, com escolaridade média e baixo nível socioeconômico. Encontrou-se na competição uma atitude favorável por ser e saber fazer, prevalecendo o bom tratamento, a justiça e o respeito. A competência conhecimento apresentou atitude desfavorável, caracterizada por conhecimento limitado sobre a patologia, habilidades, técnicas e habilidades insuficientes para cumprir suas funções e estratégias utilizadas. Conclusões: É necessário qualificar o cuidador no cuidado ao paciente com AVC, por meio de programas que potencializem a competência de ser, saber e saber fazer.

Calidad de vida relacionada con la salud y los estados de ánimo en estudiantes de instituciones educativas de Antioquia, Colombia / Quality of life related to the health and mood states of students in educational institutions from Antioquia, Colombia / Qualidade de vida relacionada à saúde e ao humor em estudantes de instituições de ensino em Antioquia, Colômbia

Introducción: La calidad de vida relacionada con la salud (CVRS) y los estados de ánimo son indicadores cruciales del bienestar en adolescentes, pero su relación con estudiantes de Antioquia, Colombia, no ha sido ampliamente estudiada. Objetivo: Determinar la CVRS y los estados de ánimo en escolares de Antioquia-Colombia. Materiales y métodos: Estudio transversal con 1957 escolares de 9 a 20 años. Se aplicaron mediciones de CVRS, ansiedad, depresión, hostilidad y alegría, actividad física, comportamiento sedentario, apoyo social de padres y nivel socioeconómico. Resultados: La calidad de vida alta (CVA) es más elevada en hombres, personas con alegría, estudiantes con apoyo de padres, activos físicamente y personas de nivel socioeconómico alto y medio. AL aumentar un año de edad, disminuye en un 15 % la CVA, y al aumentar la depresión, la ansiedad y el comportamiento sedentario disminuye la CVA. Además, los niveles de depresión y ansiedad son mayores en mujeres, estudiantes mayores, sin apoyo de los padres y personas sedentarias. Conclusiones: La CVRS se asocia con estados de ánimo, actividad física, comportamiento sedentario y apoyo de los padres; mientras que los estados de ánimo se asocian con el sexo, el apoyo de los padres, la CVS y el sedentarismo.

Introduction: Even though health-related quality of life (HRQL) and mood states are key indicators of the well-being of adolescents, their relationship has not been analyzed in students from Antioquia, Colombia. Objective: To determine HRQL and mood states in schoolchildren from Antioquia. Materials and methods: A cross-sectional study was conducted on 1,957 schoolchildren and adolescents aged between 9 and 20 years. Measurements of HRQL, anxiety, depression, hostility and happiness, physical activity, sedentary behavior, parental social support, and socioeconomic status were applied. Results: A high quality of life (HQL) was observed more frequently in male participants, students with parental support, physically active, and those belonging to medium and high socioeconomic status. HQL decreased 15% as their age increased by one year. Also, HQL was reduced when depression, anxiety, and sedentary behavior increased. Furthermore, depression and anxiety levels were higher in women, older students, as well as in those without parental control and with sedentary behavior. Conclusions: HRQL is associated with mood states, physical activity, sedentary behavior, and parental support. In contrast, mood states are related to gender, parental support, HQL, and sedentary lifestyle.

Introdução: A qualidade de vida relacionada à saúde (CVRS) e os estados de humor são indicadores cruciais de bem-estar em adolescentes, mas sua relação com estudantes de Antioquia, Colômbia, não foi amplamente estudada. Objetivo: Determinar a CVRS e os estados de humor em escolares de Antioquia-Colômbia. Materiais e métodos: Estudo transversal com 1.957 escolares de 9 a 20 anos. Foram aplicadas medidas de QVRS, ansiedade, depressão, hostilidade e felicidade, atividade física, comportamento sedentário, apoio social dos pais e nível socioeconômico. Resultados: A alta qualidade de vida (CVA) é maior em homens, pessoas com alegria, estudantes com apoio parental, fisicamente ativos e pessoas de nível socioeconômico alto e médio. À medida que a idade aumenta em um ano, diminui em 15% o CVA, e ao aumentar a depressão, a ansiedade e o comportamento sedentário aumentam, o CVA diminui. Além disso, os níveis de depressão e ansiedade são mais elevados nas mulheres, nos estudantes mais velhos, sem apoio dos pais e nas pessoas sedentárias. Conclusões: A QVRS está associada a estados de humor, atividade física, comportamento sedentário e apoio parental; enquanto os estados de humor estão associados ao sexo, apoio parental, CVS e estilo de vida sedentário.

Periodontal therapy for hopeless mandibular anterior teeth: a retrospective case report with a multidisciplinary approach and a 20-year follow-up

Introduction: This case report presents the intentional periodontal maintenance of two periodontal hopeless lower central incisors with a multidisciplinary approach and 20-year follow-up. Case presentation: A 36-year-old male, in 2001, was diagnosed with aggressive periodontitis, gingival swelling, bleeding, and mandibular central incisors with mobility and poor prognosis. Following periodontal therapy (phase I), root canal treatment, and occlusal adjustment, #31 and #41 were gently extracted to remove the granulation tissues, calculus, and infected cementum from the root surface. Then, tetracycline-HCl was applied for 5 minutes on the root surfaces. The teeth were repositioned into the sockets and splinted with a lingual bar. At 3 months, the bar was removed, and a free gingival autogenous graft was done to improve the local keratinized tissue width. Mobility scores, pocket depths, and clinical attachment levels were recorded, and radiographs were taken at 1, 5, and 20 years. The 5-year follow-up showed that the teeth were clinically and radiographically in function. There was a reduction in probing depth and a gain in clinical attachment and radiographic alveolar bone levels. After 20 years, #41 was stable, but #31 had external root resorption, leading to a new treatment plan (dental implants) and extraction. Conclusion: The clinical result of this case was satisfactory for 20 years. Intentional periodontal maintenance of the teeth may be an alternative treatment, even considering the high level of complexity.

Virtual planning as a resource for correcting severe facial asymmetry ­ case report / Planejamento virtual como recurso para correção de assimetria facial severa ­ relato de caso

A hiperplasia hemimandibular é responsável por prejuízos estéticos, funcionais, motores e psicossociais. Com etiologia incerta, ocorre frente ao desequilíbrio de fatores regulatórios de crescimento presentes na camada cartilaginosa do côndilo. O relato objetiva descrever a tomada de decisões baseada em exames complementares específicos aliados à adequada intervenção cirúrgica da lesão. Paciente gênero feminino, 33 anos de idade, compareceu à clínica particular com queixa principal de "face assimétrica", foi requerido uma avaliação cintilográfica objetivando e confirmando a interrupção do crescimento condilar, descartando a hipótese de Osteocondroma e condilectomia. Após preparo ortodôntico prévio, os exames tomográficos foram utilizados na criação de um protótipo que foi impresso após a realização dos movimentos ósseos planejados. Mediante à reconstrução, foi concluído que a assimetria presente não seria totalmente corrigida somente através da intervenção ortognática, sendo necessária também uma osteotomia removendo parte da base do corpo e ângulo mandibular, através da confecção de um guia de corte, promovendo à reanatomização sem a necessidade de acesso extra oral submandibular, evitando uma cicatriz em face feminina. Paciente encontra-se em pós-operatório de 60 meses, sem queixas e satisfeita. Portanto, é evidenciado cada vez mais a influência positiva que o planejamento virtual pode trazer aos profissionais na otimização dos resultados cirúrgicos.

Hemimandibular hyperplasia is responsible for aesthetic, functional, motor, and psychosocial impairments. With an uncertain etiology, it occurs due to the imbalance of regulatory growth factors present in the cartilaginous layer of the condyle. The report aims to describe decision-making based on specific complementary exams combined with the appropriate surgical intervention for the condition. A 33-year-old female patient presented at a private clinic with the main complaint of "asymmetric face." A scintigraphic evaluation was requested to objectively confirm the interruption of condylar growth, ruling out the hypothesis of Osteochondroma and condylectomy. After prior orthodontic preparation, tomographic exams were used to create a prototype that was printed after planned bone movements. Through the reconstruction, it was concluded that the existing asymmetry would not be entirely corrected through orthognathic intervention alone, necessitating also an osteotomy to remove part of the base of the body and mandibular angle. This was done through the creation of a cutting guide, allowing for reanatomization without the need for submandibular extraoral access, thus avoiding a scar on the female face. The patient is 60 months postoperative, with no complaints and satisfied. Therefore, the increasingly positive influence of virtual planning on optimizing surgical outcomes for professionals is evident.

Percepção profissional sobre tratamento endodôntico em sessão única e múltiplas sessões / Professional perception of single and multi-session endodontic treatment

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.

Práticas integrativas e complementares de saúde em Sergipe / Integrative and complementary health practices in Sergipe

A atenção primária em saúde (APS) é o primeiro nível de atenção em saúde, sendo um elo entre a população e o setor de saúde. Tem-se buscado a humanização dos atendimentos, e essa mudança, refletida pelas mudanças da sociedade, trouxe a implementação da Política Nacional de Práticas Integrativas e Complementares (PNPIC) no SUS. O objetivo deste trabalho foi realizar uma análise da tendência da quantidade das práticas integrativas e complementares realizadas nas regionais de saúde de Sergipe de 2017 a 2023, associando com a cobertura da atenção primária. Foi realizada análise de dados secundários através do Departamento de Informática do Sistema Único de Saúde (DATASUS), como forma de organização no período de junho/2015 a junho/2023 por regional de saúde de Sergipe. As análises dos dados foram descritivas e de correlação e por meio de análise de série temporal. A regional de saúde de Lagarto foi a que mais executou as práticas integrativas e complementares no período analisado e algumas regionais não tiveram continuidade na realização destas práticas. A regional de saúde com maior cobertura de APS foi Itabaiana. Não foi possível observar associação entre o número de práticas e a cobertura de atenção primária. Com o intuito de que o atendimento aos indivíduos seja cada vez mais humanizado, e em virtude da realização das práticas integrativas ter baixo índice ou descontinuidade em algumas regiões de Saúde de Sergipe, é relevante que os profissionais de saúde busquem conhecimentos sobre essas práticas, como também, os gestores em saúde incentivem esta ação.

Primary health care (PHC) is the first level of health care, being a link between the population and the health sector. The aim has been to humanize care, and this change, reflected by changes in society, has led to the implementation of the National Policy on Integrative and Complementary Practices (PNPIC) in the SUS. The objective of this work was to carry out an analysis of the trend in the number of integrative and complementary practices carried out in the health regions of Sergipe from 2017 to 2023, associating it with primary care coverage. Secondary data analysis was carried out through the Department of Informatics of the Unified Health System (DATASUS), as a form of organization from June/2015 to June/2023 by health region in Sergipe. Data analyzes were descriptive and correlational and through time series analysis. The Lagarto health region was the one that carried out the most integrative and complementary practices in the period analyzed and some regions did not continue to carry out these practices. The health region with the highest PHC coverage was Itabaiana. Observing an association between the number of practices and primary care coverage was impossible. With the aim that care for individuals is increasingly humanized, and because the implementation of integrative practices has a low rate or discontinuity in some Health regions of Sergipe, health professionals must seek knowledge about these practices as well as health managers encourage this action.

Uso do laser de baixa potência para o tratamento de parestesia: uma revisão de literatura / Use of low-level laser to treat paresthesia: a literature review

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.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders: drug stability, targeting efficiency, and safety.

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross the blood-brain barrier hampers the clinical translation of these therapeutic strategies. Liposomes are nanoparticles composed of lipid bilayers, which can effectively encapsulate drugs and improve drug delivery across the blood-brain barrier and into brain tissue through their targeting and permeability. Therefore, they can potentially treat traumatic and nontraumatic central nervous system diseases. In this review, we outlined the common properties and preparation methods of liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, and microfluidics techniques. Afterwards, we comprehensively discussed the current applications of liposomes in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and brain tumors. Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials. Additionally, their application as drug delivery systems in clinical practice faces challenges such as drug stability, targeting efficiency, and safety. Therefore, we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Prolonged intermittent theta burst stimulation restores the balance between A2AR- and A1R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease.

JOURNAL/nrgr/04.03/01300535-202507000-00027/figure1/v/2024-09-09T124005Z/r/image-tiff An imbalance in adenosine-mediated signaling, particularly the increased A2AR-mediated signaling, plays a role in the pathogenesis of Parkinson's disease. Existing therapeutic approaches fail to alter disease progression, demonstrating the need for novel approaches in PD. Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease. However, the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown. The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling. Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test. Immunoblot, quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen. Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals. A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen. Treatment with intermittent theta burst stimulation began 7 days after the lesion, coinciding with the onset of motor symptoms. After treatment with prolonged intermittent theta burst stimulation, complete motor recovery was observed. This improvement was accompanied by downregulation of the eN/CD73-A2AR pathway and a return to physiological levels of A1R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation. Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A1R and elevated the expression of A2AR. Intermittent theta burst stimulation reversed these effects by restoring the abundances of A1R and A2AR to control levels. The shift in ARs expression likely restored the balance between dopamine-adenosine signaling, ultimately leading to the recovery of motor control.

FUBP3 mediates the amyloid-ß-induced neuronal NLRP3 expression.

JOURNAL/nrgr/04.03/01300535-202507000-00028/figure1/v/2024-09-09T124005Z/r/image-tiff Alzheimer's disease is characterized by deposition of amyloid-ß, which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from amyloid-ß deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3 in vitro and in vivo, and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-ß is present. In the brains of aged wild-type mice and a mouse model of Alzheimer's disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5' end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-ß-to-phospho-tau transition than microglial NLRP3, and that amyloid-ß fundamentally alters the regulatory mechanism of NLRP3 expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Generating ESC-Derived RGCs for Cell Replacement Therapy.

In several ocular diseases, degeneration of retinal neurons can lead to permanent blindness. Transplantation of stem cell (SC)-derived RGCs has been proposed as a potential therapy for RGC loss. Although there are reports of successful cases of SC-derived RGC transplantation, achieving long-distance regeneration and functional connectivity remains a challenge. To address these hurdles, retinal organoids are being used to study the regulatory mechanism of stem cell transplantation. Here we present a modified protocol for differentiating human embryonic stem cells (ESCs) into retinal organoids and transplanting organoid-derived RGCs into the murine eyes.

Trabecular Meshwork Regeneration for Glaucoma Treatment Using Stem Cell-Derived Trophic Factors.

Glaucoma is one of the leading causes of irreversible blindness. Stem cell therapy has shown promise in the treatment of primary open-angle glaucoma in animal models. Stem cell-free therapy using stem cell-derived trophic factors might be in demand in patients with high-risk conditions or religious restrictions. In this chapter, we describe methods for trabecular meshwork stem cell (TMSC) cultivation, secretome harvesting, and protein isolation, as well as assays to ensure the health of TMSC post-secretome harvesting and for secretome periocular injection into mice for therapeutic purposes.

Retinal Explant Culture from Mouse, Human, and Nonhuman Primates and Its Applications in Vision Research.

The retinal explant culture system is a valuable tool for studying the pharmacological, toxicological, and developmental aspects of the retina. It is also used for translational studies such as gene therapy. While no photoreceptor-like cell lines are available for in vitro studies of photoreceptor cell biology, the retinal explant culture maintains the laminated retinal structure ex vivo for as long as a month. Human and nonhuman primate (NHP) postmortem retinal explants cut into small pieces offer the possibility of testing multiple conditions for safety and adeno-associated viral (AAV) vector optimization. In addition, the cone-enriched foveal area can be studied using the retinal explants. Here, we present a detailed working protocol for retinal explant isolation and culture from mouse, human, and NHP for testing drug efficacy and AAV transduction. Future applications of this protocol include combining live imaging and multiwell retinal explant culture for high-throughput drug screening systems in rodent and human retinal explants to identify new drugs against retinal degeneration.

Chromatographic Purification and Polishing of AAV Particles.

The production of Adeno-associated virus (AAV) vectors in the lab setting has typically involved expression in adherent cells followed by purification through ultracentrifugation in density gradients. This production method is, however, not easily scalable, presents high levels of cellular impurities that co-purify with the virus, and results in a mixture of empty and full capsids. Here we describe a detailed AAV production protocol that overcomes these limitations through AAV expression in suspension cells followed by AAV affinity purification and AAV polishing to separate empty and full capsids, resulting in high yields of ultra-pure AAV that is highly enriched in full capsids.

Engineering mesoporous polydopamine-based potentiate STING pathway activation for advanced anti-biofilm therapy.

The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.

Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates unique characteristics in anticancer therapies as it selectively induces apoptosis in cancer cells. However, most cancer cells are TRAIL-resistant. Odanacatib (ODN), a cathepsin K inhibitor, is considered a novel sensitizer for cancer treatment. Combination therapy between TRAIL and sensitizers is considered a potent platform that improves TRAIL-based anticancer therapies beyond TRAIL monotherapy. Herein, we developed ODN loaded poly(lactic-co-glycolic) nanoparticles conjugated to GST-TRAIL (TRAIL-ODN-PLGA-NPs) to target and treat TRAIL-resistant cancer. TRAIL-ODN-PLGA-NPs demonstrated a significant increase in cellular uptake via death receptors (DR5 and DR4) on surface of cancer cells. TRAIL-ODN-PLGA-NPs exposure destroyed more TRAIL-resistant cells compared to a single treatment with free drugs. The released ODN decreased the Raptor protein, thereby increasing damage to mitochondria by elevating reactive oxygen species (ROS) generation. Additionally, Bim protein stabilization improved TRAIL-resistant cell sensitization to TRAIL-induced apoptosis. The in vivo biodistribution study revealed that TRAIL-ODN-PLGA-NPs demonstrated high location and retention in tumor sites via the intravenous route. Furthermore, TRAIL-ODN-PLGA-NPs significantly inhibited xenograft tumor models of TRAIL-resistant Caki-1 and TRAIL-sensitive MDA-MB-231 cells.The inhibition was associated with apoptosis activation, Raptor protein stabilizing Bim protein downregulation, Bax accumulation, and mitochondrial ROS generation elevation. Additionally, TRAIL-ODN-PLGA-NPs affected the tumor microenvironment by increasing tumor necrosis factor-α and reducing interleukin-6. In conclusion, we evealed that our formulation demonstrated synergistic effects against TRAIL compared with the combination of free drug in vitro and in vivo models. Therefore, TRAIL-ODN-PLGA-NPs may be a novel candidate for TRAIL-induced apoptosis in cancer treatment.

Astroglial membrane camouflaged Ptbp1 siRNA delivery hinders glutamate homeostasis via SDH/Nrf2 pathway.

Polypyrimidine tract-binding protein 1 (PTBP1) regulates numerous alternative splicing events during tumor progression and neurogenesis. Previously, PTBP1 downregulation was reported to convert astrocytes into functional neurons; however, how PTBP1 regulates astrocytic physiology remains unclear. In this study, we revealed that PTBP1 modulated glutamate uptake via ATP1a2, a member of Na+/K+-ATPases, and glutamate transporters in astrocytes. Ptbp1 knockdown altered mitochondrial function and energy metabolism, which involved PTBP1 regulating mitochondrial redox homeostasis via the succinate dehydrogenase (SDH)/Nrf2 pathway. The malfunction of glutamate transporters following Ptbp1 knockdown resulted in enhanced excitatory synaptic transmission in the cortex. Notably, we developed a biomimetic cationic triblock polypeptide system, i.e., polyethylene glycol44-polylysine30-polyleucine10 (PEG44-PLL30-PLLeu10) with astrocytic membrane coating to deliver Ptbp1 siRNA in vitro and in vivo, which approach allowed Ptbp1 siRNA to efficiently cross the blood-brain barrier and target astrocytes in the brain. Collectively, our findings suggest a framework whereby PTBP1 serves as a modulator in glutamate transport machinery, and indicate that biomimetic methodology is a promising route for in vivo siRNA delivery.

Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma.

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.