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179 result(s) for "Alves da Silva, Pedro Henrique"
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A monoclonal antibody that inhibits the shedding of CD16a and CD16b and promotes antibody-dependent cellular cytotoxicity against tumors
CD16a triggers antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis by natural killer (NK) cells and macrophages in anti-tumor immunity. However, CD16a undergoes cleavage by ADAM17 that dampens its anti-tumor immunity. We here develop a monoclonal antibody (F9H4) that binds to CD16a and inhibits its cleavage. F9H4 retains CD16a on the surface of NK cells and macrophages, without triggering or blocking CD16a. F9H4 also binds to and inhibits shedding of CD16b by neutrophils, and inhibits CD16a/b shedding by leukocytes in tumor samples from lung cancer patients. F9H4 promotes ADCC against lung cancer cells that are opsonized by cetuximab, an epidermal growth factor receptor antibody that engages CD16a. F9H4 synergizes with cetuximab to inhibit human lung adenocarcinoma development in immunodeficient mice reconstituted with human NK cells. F9H4 combining with cetuximab also inhibits murine lung carcinoma growth in Fc gamma receptor-humanized mice, and such effect is mediated by NK cells and macrophages. The efficacy of F9H4+cetuximab in lung cancer models is the proof-of-concept for this new approach that promotes anti-tumor functions of Fc-enabled antibodies. CD16a triggers antibody-dependent cellular cytotoxicity but CD16a shedding dampens its anti-tumor activity. Here the authors develop a monoclonal antibody (F9H4) that prevents CD16a shedding, which synergizes with a tumor cell opsonizing antibody (cetuximab) to elicit natural killer cell-driven immunity.
Unraveling the Complexity of Seizures and Epilepsies: a Multifaceted Approach to Classification, Syndromes, Causes, and Integrated Therapies
Objective: To investigate the clinical diversity, genetic bases, diagnostic complexity, and therapeutic approaches of epileptic syndromes, highlighting recent advances in understanding these disorders.   Theoretical Framework: Epileptic syndromes are neurological disorders characterized by recurrent epileptic seizures, resulting from abnormal neuronal activity in the brain, whose classification has evolved towards clinical and genetic criteria.   Method: A systematic approach was employed for bibliographic review on epileptic syndromes, consulting biomedical databases and applying strict selection criteria. Studies addressing clinical diversity, genetic bases, and diagnostic complexity were included, followed by qualitative data analysis to identify patterns and gaps in the literature.   Results and Discussion: Results reveal evident genetic heterogeneity, with some syndromes exhibiting well-defined genetic bases. Advances in genomics and molecular neurobiology have provided insights into pathogenic mechanisms, despite persistent challenges, including resistance to conventional medications.   Implications of the Research: In-depth understanding is crucial for accurate diagnosis and effective therapeutic development, emphasizing the continuous need for research to improve clinical outcomes and quality of life for patients.   Originality/Value: Highlights recent advances in understanding epileptic syndromes, identifying key areas for future research, and contributing to better comprehension and quality of life for affected patients.
Pathogenesis, Articular Protective Mechanisms, and Risk Factors in Osteoarthritis: a Systematic Review
Objective: The objective of this study is to present a systematic review on the pathogenesis, joint protective mechanisms, and risk factors in osteoarthritis (OA), aiming to provide a comprehensive and updated view that contributes to clinical practice and the understanding of this complex condition.   Theoretical Framework: This section presents the main concepts and theories that underpin the research on osteoarthritis. Theories on joint degeneration, protective mechanisms of joints, and associated risk factors are highlighted, providing a solid foundation for understanding the context of the investigation.   Method: The methodology adopted for this research comprises a systematic review using a rigorous approach in various biomedical databases, including PubMed, Scopus, and Google Scholar, without language or publication date restrictions. Study selection was based on specific exclusion criteria, focusing on aspects related to pathogenesis, protective mechanisms, and risk factors in OA. Data analysis was qualitative, identifying patterns, trends, and gaps in the literature.   Results and Discussion: The results revealed that joint protective mechanisms are essential for maintaining the structural integrity of joints, including elements such as the joint capsule, ligaments, muscles, tendons, and synovial fluid. Articular cartilage, composed of type II collagen and proteoglycans, is crucial in joint biomechanics. In OA, progressive changes in cartilage, such as aggrecan depletion and type II collagen disorganization, compromise its ability to absorb impacts and resist mechanical stress. The main identified risk factors include advanced age, female gender, genetic predisposition, anatomical abnormalities, significant joint injuries, and joint misalignment.   Research Implications: The practical and theoretical implications of this research are discussed, providing insights into the development of effective therapeutic and preventive strategies for osteoarthritis. The findings can influence clinical practices and guide future research in the field.   Originality/Value: This study contributes to the literature by providing a comprehensive and updated systematic review on the pathogenesis, joint protective mechanisms, and risk factors in OA. The relevance and value of this research are evidenced by the potential application of the results in improving treatment and prevention strategies for osteoarthritis.
ALLERGIC CONTACT DERMATITIS: CAUSES, SYMPTOMS, AND SPECIFIC THERAPIES
Objetivo: Este estudo tem como objetivo analisar a Dermatite de Contato Alérgica (DCA), explorando sua etiologia, mecanismos patogênicos, diagnóstico diferencial e opções terapêuticas contemporâneas para melhorar a gestão clínica e a qualidade de vida dos pacientes. Referencial Teórico: A pesquisa se baseia na compreensão dos mecanismos imunológicos, especificamente a sensibilização dos linfócitos T de memória, que são cruciais na patogênese da DCA após exposição a alérgenos. A revisão da literatura também aborda a variedade de agentes causadores, desde produtos químicos até componentes naturais. Método: A metodologia emprega uma revisão sistemática da literatura e estudos de caso para investigar as características clínicas e resposta ao tratamento da DCA. O patch test é destacado como ferramenta diagnóstica principal para identificar alérgenos específicos responsáveis pela condição. Resultados e Discussão: Os resultados enfatizam a importância do diagnóstico preciso e da identificação dos alérgenos através do patch test, facilitando a evitação eficaz dos mesmos. As estratégias terapêuticas recomendadas incluem corticosteroides tópicos, emolientes, anti-histamínicos e, em casos necessários, antibióticos, com adaptações conforme a severidade e localização das lesões. Implicações da Pesquisa: Este estudo sublinha a necessidade de uma abordagem holística e multidisciplinar no tratamento da DCA, propondo uma integração entre avanços científicos e práticas clínicas para um manejo mais efetivo da doença. Originalidade/Valor: A originalidade deste trabalho reside na sua abordagem detalhada do diagnóstico diferencial e nas recomendações terapêuticas adaptativas, contribuindo significativamente para a literatura existente e para a prática clínica no manejo da DCA.
Skin Grafts in Plastic Surgery: A Comprehensive Review of Procedures, Techniques, and Clinical Considerations
Objective: This study aims to analyze the progress and challenges related to the use of skin grafts in plastic surgery, with the purpose of providing a comprehensive understanding of the associated techniques and clinical considerations.   Theoretical Framework: A review of the fundamentals of plastic surgery is presented, emphasizing the importance of skin grafts in wound and deformity reconstruction, as well as exploring the impact of tissue engineering on the evolution of these techniques.   Method: This study is based on a systematic review of the scientific literature, following recognized guidelines. Relevant articles addressing different types of skin grafts, their clinical applications, and associated procurement techniques were selected.   Results and Discussion: The results of the review highlight the variety of skin grafts available and their respective indications. The discussion addresses the challenges in selecting the appropriate type of graft and the ethical issues related to its procurement and use.   Implications of the Research: This study offers important insights for plastic surgeons and researchers on best practices in skin graft utilization, emphasizing the need for ethical considerations and specific care in graft selection and procurement.   Originality/Value: It contributes to the literature by providing a comprehensive analysis of skin graft techniques in plastic surgery, including recent advancements and emerging issues. Its relevance lies in the practical guidance it offers to professionals in the field.
Allergic Contact Dermatitis: Causes, Symptoms, and Specific Therapies
Objective: The present study aims to deepen understanding of Allergic Contact Dermatitis (ACD), exploring its etiology, immunological mechanisms, diagnostic methods, and updated therapeutic strategies to improve treatment and quality of life for patients.   Theoretical Framework: The research is grounded in studies of the immunological processes involved in ACD, with an emphasis on the sensitization of memory T lymphocytes, and the diversity of causative agents, ranging from chemicals to natural substances.   Method: A methodological approach that includes a systematic literature review and analysis of relevant case studies was adopted, with special attention to the use of the patch test as a diagnostic tool for identifying specific allergens.   Results and Discussion: The findings highlight the importance of accurate diagnosis and correct identification of allergens via patch test, which are essential for effective disease management. Therapeutic options discussed range from topical corticosteroids to antihistamines, adjusted according to the severity of clinical manifestations.   Research Implications: This study underscores the importance of a multidisciplinary and evidence-based management approach in addressing ACD, integrating the latest scientific advances into daily clinical practices.   Originality/Value: The original contribution of this article lies in the integrative analysis and detailed practical recommendations for the treatment of ACD, providing new perspectives for the medical literature and clinical treatment of this complex condition.
Advancing Cancer Immunotherapy Using Lipid Nanoparticle-Based Approaches
Cancer immunotherapy, including adoptive cell therapies, cancer vaccines, and cytokine-based therapies, have revolutionized targeted approaches in the treatment of different tumors. However, the broader application of immunotherapies, such as for engineered T cells expressing a chimeric antigen receptor (CAR-T cells), remains limited by challenges in production, systemic toxicity, and inefficient delivery, especially in solid tumors. Recent advances in nucleic acid delivery technologies, notably ionizable lipid nanoparticles (LNP), offer promising solutions to overcome these barriers. LNPs have shown potential in delivering messenger RNA (mRNA), and DNA for the generation of CAR-T cells, cancer vaccines, bispecific antibodies, and cytokine-based immunotherapies. The clinical success of LNP-based platforms in mRNA COVID-19 vaccines and interference RNA therapies for genetic disorders further validates their effectiveness in gene delivery, highlighting LNPs as versatile carriers for therapeutic nucleic acids. Furthermore, LNPs can be optimized for off-the-shelf formulations, enabling personalized treatments targeting specific patient needs. In this review, we highlight the role of LNP platforms in advancing mRNA and DNA delivery for cancer immunotherapy. We explore their potential to improve CAR-T cell production, advance cancer vaccines, and support the development of bispecific antibody- and cytokine-based therapies, ultimately paving the way for more effective, scalable, and accessible immunotherapeutic strategies.
Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes
The vaccinia virus (VACV) is the most studied and well-characterised member of the Poxviridae family. However, the mechanisms through which it modulates redox homeostasis in host cells remain unclear. Although oxidative stress, which is marked by elevated levels of reactive species, contributes to the pathogenesis of many viral infections, poxviruses may adopt distinct strategies. VACV has redox effector proteins that are released into the cytosol when the virus penetrates the host cell. This study demonstrates for the first time that VACV infection leads to the activation of the nuclear factor erythroid 2 (Nrf2)/antioxidant response element pathway, a key regulator of cellular antioxidant responses, a mechanism not previously described for any poxvirus. Using BSC-40 cells, we observed that VACV significantly reduced reactive oxygen and nitrogen species levels, downregulated inducible nitric oxide synthase, and enhanced the activity of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. This antioxidant shift is correlated with increased Nrf2 activity and the upregulation of its downstream targets. This virus-induced antioxidant state may be an immunomodulatory mechanism that facilitates viral replication by dampening host defence. Thus, our findings expand the current understanding of virus–host interactions in poxvirus infections.
Anterior Knee Pain After Anterior Cruciate Ligament Reconstruction
Background: Anterior knee pain is a frequent condition after anterior cruciate ligament reconstruction (ACLR), but its origin remains uncertain. Studies have suggested that donor site morbidity in autologous bone–patellar tendon–bone reconstructions may contribute to patellofemoral pain, but this does not explain why hamstring tendon reconstructions may also present with anterior pain. Purpose: To evaluate the prevalence of anterior knee pain after ACLR and its predisposing factors. Study Design: Case-control study; Level of evidence, 3. Methods: We evaluated the records of all patients who underwent ACLR between 2000 and 2016 at a private facility. The prevalence of anterior knee pain after surgery was assessed, and possible risk factors (graft type, patient sex, surgical technique, range of motion) were evaluated. Results: The records of 438 patients (mean age, 30 years) who underwent ACLR were analyzed. Anterior knee pain was found in 6.2% of the patients. We found an increased prevalence of anterior knee pain with patellar tendon graft, with an odds ratio of 3.4 (P = .011). Patients who experienced extension deficit in the postoperative period had an odds ratio of 5.3 of having anterior pain (P < .001). Anterior knee pain was not correlated with patient sex or surgical technique. Conclusion: The chance of having anterior knee pain after ACLR was higher when patellar tendon autograft was used compared with hamstring tendon graft, as well as in patients who experienced extension deficit in the postoperative period.
Development and Automation of a Photovoltaic-Powered Soil Moisture Sensor for Water Management
The objective of this study was to develop and calibrate a photovoltaic-powered soil moisture sensor (SMS) for irrigation management. Soil moisture readings obtained from the sensor were compared with gravimetric measurements. An automated SMS was used in two trials: (i) okra crop (Abelmoschus esculentus) and (ii) chili pepper (Capsicum frutescens). All sensors were calibrated and automated using an Arduino Mega board with C++. The soil moisture data were subjected to descriptive statistical analysis. The data recorded by the equipment was correlated with the gravimetric method. The determination coefficient (R2), Pearson correlation (r), and root mean square error (RMSE) were adopted as criteria for equipment validation. The results show that our SMS achieved an R2 value of 0.70 and an r value of 0.84. Notably, there was a striking similarity observed between SMS and gravimetric data, with RMSE values of 3.95 and 4.01, respectively. The global model developed exhibited highly efficient outcomes with R2 (0.98) and r (0.99) values. The applicability of the developed SMS facilitates irrigation management with accuracy and real-time monitoring using digital data. The automation of the SMS emerges as a real-time and precise alternative for performing irrigation at the right moment and in the correct amount, thus avoiding water losses.