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.

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.

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.

Desafios e mudanças no processo de trabalho das equipes de saúde da família no cenário pandêmico: relato de experiência / Challenges and changes in the work process of family health teams in the pandemic scenario: experience report

O presente estudo tem por objetivo realizar um relato de experiência demonstrando a percepção de discentes do curso de odontologia na sua participação na prática da atenção primária à saúde (APS), vivenciadas em um cenário pandêmico e com base no combate a enfrentamentos e desafios impostos no processo de trabalho das equipes de saúde da família. Este estudo trata - se de relato de experiência, de caráter descritivo e retrospectivo, associado à uma pesquisa bibliográfica para que trousse o embasamento teórico necessário para a descrição do relato de experiência vivenciado. No decorrer da pandemia, a Equipe de saúde da família exerceu importante papel e atuou na linha de prevenção e controle desta, sendo uma das maiores ferramentas de apoio. Na odontologia, a atuação da equipe de saúde bucal devido a fatores de risco inerentes à esta modalidade de ocupação, ficou limitada em seu exercício. O conhecimento de muitos dos profissionais da rede pública foi colocado em questão, assim como sua vivência, limitações e o medo de contrair a doença. Os profissionais da equipe de saúde, mostraram que o trabalho interprofissional e um bom relacionamento aumentou o incentivo e a responsabilidade de equipe.

This study aims to carry out an experience report demonstrating the perception of students of the dentistry course in their participation in the practice of primary health care (PHC), experienced in a pandemic scenario and based on the fight against confrontations and challenges imposed on the work process of family health teams. This study is an experience report, descriptive and retrospective, associated with bibliographical research to bring the necessary theoretical basis for the description of the lived experience report. During the pandemic, the Family Health Team played an important role and acted in the line of prevention and control of this, being one of the greatest support tools. In dentistry, the performance of the oral health team, due to risk factors inherent to this type of occupation, was limited in its exercise. The knowledge of many public health professionals was questioned, as well as their experience, limitations and fear of contracting the disease. Health team professionals showed that interprofessional work and a good relationship increased team incentive and responsibility.

O emprego da moldagem digital na prática odontológica - relato de caso / The use of digital molding in dental practice ­ case report

O avanço da tecnologia de digitalização de imagens e desenvolvimento de dispositivos de fresagem possibilitaram a otimização de diversos processos na Odontologia. O emprego do escaneamento intraoral e do sistema CAD-CAM (CAD - Computer Aided Design; CAM - Computer Aided Manufacturing) aprimorou a realização de reabilitações protéticas, permitindo a obtenção de peças de alta qualidade em tempo reduzido. O objetivo deste trabalho é relatar um caso de reabilitação de um incisivo central inferior a partir de escaneamento intraoral, com scanner Omnicam (DentsplySirona Charlotte, NC, EUA) e aplicação do sistema CAD-CAM.

The advancement of image digitization technology and the development of milling devices have made it possible to optimize various processes in Dentistry. The use of intraoral scanning and the CAD-CAM system (CAD - Computer Aided Design; CAM - Computer Aided Manufacturing) has improved the performance of prosthetic rehabilitations, allowing the obtaining of high quality parts in a reduced time. The objective of this work is to report a case of rehabilitation of a lower central incisor using intraoral scanning, with an Omnicam scanner (Dentsply Sirona) and application of the CAD-CAM system.

Percepção de aprendizagem on-line na disciplina de biomateriais / Perception of online learning in the biomaterials course

Com as universidades fechadas e a implementação do Ensino Remoto Emergencial, as atividades curriculares ocorreram através de plataformas digitais. O objetivo do presente trabalho foi avaliar a percepção de aprendizagem on-line na disciplina de Biomateriais da Faculdade de Odontologia da Universidade Federal Fluminense no período da pandemia. O questionário COLLES (Constructivist OnLine Learning Environment Survey) foi enviado individualmente por e-mail aos cinquenta alunos, apresentando 24 declarações divididas em seis quesitos: relevância, reflexão crítica, interatividade, apoio dos tutores, apoio entre os colegas e compreensão; e para cada declaração cinco opções de resposta: quase sempre, frequentemente, algumas vezes, raramente e quase nunca. Quarenta e um alunos responderam. A soma das médias obtidas em quase sempre e frequentemente foi de 87,2% para relevância, 70% para reflexão crítica, 33,9% para interatividade, 47,6% para apoio dos tutores, 44,2% para apoio dos colegas e 89,5% para compreensão. Concluiu-se que a relevância, a reflexão crítica e a compreensão apresentaram melhores resultados, enquanto a interatividade, o apoio entre os colegas e o apoio dos tutores demonstraram necessidade de aprimoramento. E apesar das limitações do ERE, a avaliação positiva dos alunos evidenciou esta modalidade de educação on-line como uma solução plausível.

With universities closed and the implementation of Emergency Remote Teaching, curricular activities took place through digital platforms. The objective of this study was to assess the perception of online learning in the Biomaterials course at the Dental School of the Federal Fluminense University during the pandemic. The COLLES questionnaire (Constructivist OnLine Learning Environment Survey) was individually sent via email to fifty students, presenting 24 statements divided into six aspects: relevance, critical reflection, interactivity, tutor support, peer support, and comprehension. For each statement, there were five response options: almost always, often, sometimes, rarely, and almost never. Forty-one students responded. The sum of the averages obtained for almost always and often was 87.2% for relevance, 70% for critical reflection, 33.9% for interactivity, 47.6% for tutor support, 44.2% for peer support, and 89.5% for comprehension. It was concluded that relevance, critical reflection, and comprehension showed better results, while interactivity, peer support, and tutor support demonstrated a need for improvement. Despite the limitations of Emergency Remote Teaching, the positive evaluation from the students highlighted this mode of online education as a plausible solution.

Deep learning-enabled fluorescence imaging for surgical guidance: in silico training for oral cancer depth quantification.

Significance: Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. Aim: A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. Approach: A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. Results: The performance of the CSH model was superior when presented with patient-derived tumors ( P -value < 0.05 ). The CSH model could predict depth and concentration within 0.4 mm and 0.4 µ g / mL , respectively, for in silico tumors with depths less than 10 mm. Conclusions: A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.

Ligand-free biodegradable poly(beta-amino ester) nanoparticles for targeted systemic delivery of mRNA to the lungs.

Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.

Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Conversion of albumin into a BODIPY-like photosensitizer by a flick reaction, tumor accumulation and photodynamic therapy.

The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.

Cyclic catalysis of intratumor Fe3+/2+ initiated by a hollow mesoporous iron sesquioxide nanoparticle for ferroptosis therapy of large tumors.

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 (•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 (O2•-) by LAC, and the intratumor NADPH oxidases can be activated by CDDP to generate O2•-. The O2•- 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 •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.

Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemoresistance and immune escape. We have developed a controlled-released thermosensitive hydrogel containing pH- responsive anti-CD276 scFV engineered biomimetic nanovesicles to overcome BC in primary, recurrent, metastatic and abscopal humanized mice models. Nanovesicles coated anti-CD276 scFV selectively fuses with cell membrane of senescent-escape CSCs, then sequentially delivers siCALD1 and ADR due to pH-responsive MnP shell. siCALD1 together with ADR effectively induce apoptosis of CSCs, decrease expression of CD276 and PD-L1, and upregulate MHC I combined with Mn2+ to overcome chemoresistance and promote CD8+T cells infiltration. This combined therapeutic approach reveals insights into immune surveillance evasion by senescent-escape CSCs, offering a promising strategy to immunotherapy effectiveness in cancer therapy.

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

Local delivery of platelet-derived factors mitigates ischemia and preserves ovarian function through angiogenic modulation: A personalized regenerative strategy for fertility preservation.

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).

Responsive and traceless assembly of iron nanoparticles and 131I labeled radiopharmaceuticals for ferroptosis enhanced radio-immunotherapy.

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.

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

A carrier-free nanovaccine combined with cancer immunotherapy overcomes gemcitabine resistance.

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

Liposomes-enabled cancer chemoimmunotherapy.

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.