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ABSTRACT Langerhans cell histiocytosis comprises a heterogeneous range of clinical manifestations secondary to clonal proliferation of histiocytes, characterized by the accumulation of these cells in various organs and tissues. The ophthalmological component commonly involved is the orbit. Herein, we report a rare case of Langerhans cell histiocytosis with eyelid involvement, which resulted in severe ocular surface complications, which subsequently significantly impacted the patient's quality of life. This case report highlights the fact that despite being rare, Langerhans cell histiocytosis should be included in the differential diagnosis of eyelid lesions. Furthermore, a multidisciplinary approach with a systemic overview is crucial for managing the ocular complications.
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ABSTRACT Objective: The aim of this study was to describe the epidemiological characteristics of pediatric patients with sickle cell disease (SCD) and evaluate the use of medicinal plants in these patients concomitantly with their drug treatment. Methods: This is a review of the medical records of pediatric patients at a public institution with tertiary care. The selection criterion was to be a child or adolescent with SCD undergoing pediatric follow-up at this outpatient clinic. In the medical records of the patients selected, records of the use of plants for medicinal purposes were sought. Results: In total, 154 records (100% of total active patients followed in this clinic) were reviewed: 99 children and 55 adolescents. The predominant genotype was SS (58.4%), followed by SC (29.2%). The use of at least one medication for SCD was reported in 95.5% of the medical records. The use of medicinal plants was reported by 70.1% of patients, with 276 citations in the medical records referring to 64 different types of plants. Six plants were used for the treatment of SCD, the main one being Lemonvine/Ora-pro-nóbis (Pereskia aculeata). The use of medicinal plants was reported for flu-like symptoms and/or COVID-19 (both for prevention and treatment) by 60.5% of the citations, with 35 different plants reported for this use, exclusively or not. This use was followed by pain symptoms (14.2% of citations). Conclusions: The majority of patients in this study use both conventional and traditional/complementary/alternative medicine, highlighting the need for more studies in the area, with a special focus on patient safety.
RESUMO Objetivo: Descrever as características epidemiológicas de pacientes pediátricos com doença falciforme (DF) e avaliar o uso de plantas medicinais concomitantemente ao tratamento medicamentoso. Métodos: Realizou-se revisão de prontuários de pacientes pediátricos de uma instituição pública com nível de atendimento terciário; o critério de seleção foi ser criança ou adolescente com DF em acompanhamento pediátrico neste ambulatório. Nos prontuários dos pacientes selecionados foi procurado o registro do uso de plantas com finalidades medicinais. Resultados: Foram revisados 154 prontuários (100% dos pacientes ativos desse ambulatório): 99 crianças e 55 adolescentes. O genótipo predominante foi SS (58,4%), seguido do SC (29,2%). O uso de ao menos uma medicação para a DF foi relatada em 95,5% dos prontuários. Em 70,1% dos prontuários havia o relato do uso de plantas medicinais, em 276 citações, sendo 64 plantas citadas ao todo; destas, seis espécies foram citadas para o tratamento da doença de base (DF), sendo "ora-pro-nobis" (Pereskia aculeata) a principal. Das 276 citações de plantas medicinais nos prontuários, 60,5% incluíram o uso de plantas medicinais em sintomas gripais e/ou COVID-19 (tanto prevenção quanto tratamento), sendo relatadas 35 para este uso, exclusivamente ou não. Essa foi a principal finalidade de uso encontrada nos prontuários dos pacientes, seguida do uso para sintomas de dor (14,2% das citações). Conclusões: Notou-se que a maioria dos pacientes avaliados faz uso da medicina convencional, aliada à tradicional/ complementar/ alternativa, o que leva à necessidade de mais estudos nessas áreas, especialmente na pediatria, visando principalmente à segurança do paciente.
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Studying host-pathogen interactions is essential for understanding infectious diseases and developing possible treatments, especially for priority pathogens with increased virulence and antibiotic resistance, such as Klebsiella pneumoniae. Over time, this subject has been approached from different perspectives, often using mammal host models and invasive endpoint measurements (e.g., sacrifice and organ extraction). However, taking advantage of technological advances, it is now possible to follow the infective process by noninvasive visualization in real time, using optically amenable surrogate hosts. In this line, this chapter describes a live-cell imaging approach to monitor the interaction of K. pneumoniae and potentially other bacterial pathogens with zebrafish larvae in vivo. This methodology is based on the microinjection of fluorescent bacteria into the otic vesicle, followed by time-lapse observation by automated fluorescence microscopy with environmental control, monitoring the dynamics of immune cell recruitment, bacterial load, and larvae survival.
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Interacciones Huésped-Patógeno , Infecciones por Klebsiella , Klebsiella pneumoniae , Larva , Microinyecciones , Microscopía Fluorescente , Pez Cebra , Animales , Pez Cebra/microbiología , Klebsiella pneumoniae/inmunología , Microinyecciones/métodos , Larva/microbiología , Larva/inmunología , Microscopía Fluorescente/métodos , Interacciones Huésped-Patógeno/inmunología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/inmunología , Modelos Animales de EnfermedadRESUMEN
In this paper, we present a new design for a chronoamperometric flow cell in which air bubbles do not interfere with the control of potential between the working and reference electrodes. The flow-through dual-detection cell consists of two independent parts: an upper compartment containing a quiescent supporting electrolyte solution and a channel that operates under hydrodynamically controlled conditions. In this system, the working and counter electrodes can be placed directly in contact with both compartments, whereas the reference electrode can be assembled to be either isolated or in contact with the flowing stream channel. The design ensures that the potential applied to the working electrode (controlled in the upper compartment) is similar to the potential applied in the flowing channel. The performance of the proposed flow cell in generating accurate results, even in the presence of air bubbles, was evaluated through successive air-analyte-air injections. In both series where the analyte was introduced, suitable reproducibility was achieved. The robustness of the design was definitively proven by performing a series of measurements in analytical applications for the determination of hydrogen peroxide in antiseptic samples, yielding very satisfactory results.
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This study aimed to compare the effects of two extraction techniques (conventional n-hexane and supercritical CO2) on the oil extraction yields, fatty acids profile, anti-hyaluronidase activity, oxidative stability, and in vitro bioactivities of oils from Sacha Inchi (Plukenetia volubilis). Higher oil extraction yield (99 %) was achieved using the SC-CO2, although similar fatty acids profiles were depicted between both treatments (p < 0.05). The SC-CO2 oil presented higher anti-hyaluronidase (31 %) activity, but lower oxidative stability (5.05 h) compared to the solvent extraction (10 %, and 5.3 h, respectively). In vitro assays further revealed that the best human normal colon cells (FHC) cell viability (100 %), anti-inflammatory (50 % lower NO production), and antioxidant (20 % ROS reduction) activities were consistently observed in both extraction treatments at concentrations of 50 µg/mL and higher. These findings highlight the potential of supercritical CO2 extraction in yielding Sacha Inchi oil with enhanced bioactive properties without the disadvantages of the use of organic solvents extraction.
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Cromatografía con Fluido Supercrítico , Aceites de Plantas , Cromatografía con Fluido Supercrítico/métodos , Humanos , Aceites de Plantas/química , Aceites de Plantas/farmacología , Aceites de Plantas/aislamiento & purificación , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Ácidos Grasos/química , Supervivencia Celular/efectos de los fármacos , Línea Celular , Oxidación-ReducciónRESUMEN
ABSTRACT Mantle cell lymphoma of the ocular and periorbital regions is extremely rare but should be considered in the differential diagnosis of lesions affecting the periorbital tissues. In this study, we present a rare case of mantle cell lymphoma of the lacrimal sac in a 65-year-old male presenting with a mass in the lacrimal sac region and epiphora. After clinical examinations and imaging studies, the mucocele was misdiagnosed. Considering the unexpected findings during external dacryocystorhinostomy, a frozen biopsy was performed, which confirmed the diagnosis of lymphoma.
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ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
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Objetivo: identificar o local e os cuidados diretos recebidos por pessoas com úlceras da perna por doença falciforme nos serviços de atenção à saúde. Método: estudo transversal, realizado em 11 centros, no período de agosto de 2019 a abril de 2020. Fizeram parte do estudo 72 pessoas com úlcera da perna ativa. O estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultado: apresentavam anemia falciforme 91,7% dos participantes, com mediana de três anos de existência da úlcera; 77,8% eram redicivantes; 40,3% compravam os insumos; 66,7% trocavam o próprio curativo no domicílio; 52,8% realizavam uma ou mais trocas diárias; 45,8% dos tratamentos foram prescritos pelo médico; 37,5% eram pomada (colagenase ou antibiótico); 89% não utilizavam compressão para o manejo do edema. Conclusão: a maioria dos participantes não estava inserida na Rede de Atenção à Saúde para o tratamento da úlcera, e não recebia assistência sistematizada e nem insumos apropriados.
Objective: to identify the location and direct care received by people with leg ulcers due to sickle cell disease in health care services. Method: a cross-sectional study carried out in 11 centers from August 2019 to April 2020. The study included 72 people with active leg ulcers. The study was approved by the Research Ethics Committee. Results: a total of 91.7% of the participants had sickle cell anemia, with a median of three years of ulcer existence; 77.8% were recurrent; 40.3% bought the supplies; 66.7% changed their own dressings at home; 52.8% did one or more changes a day; 45.8% of the treatments were prescribed by physician; 37.5% were ointments (collagenase or antibiotics); and 89% did not use compression to manage edema. Conclusion: most of the participants were not included in the Health Care Network for ulcer treatment and did not receive systematized care or appropriate supplies.
Objetivo: identificar el lugar y los cuidados directos recibidos por personas con úlceras de pierna por enfermedad falciforme en los servicios de atención a la salud. Método: estudio transversal, realizado en 11 centros, en el período de agosto de 2019 a abril de 2020. Participaron 72 personas con úlcera de pierna activa. El estudio fue aprobado por el Comité de Ética en Investigación. Resultado: presentaban anemia falciforme 91,7% de los participantes, con una mediana de tres años de existencia de la úlcera; 77,8% eran recidivantes; 40,3% compraban los insumos; 66,7% cambiaban su propio vendaje en el domicilio; 52,8% realizaban uno o más cambios diarios; 45,8% de los tratamientos fueron prescritos por el médico; 37,5% eran pomada (colagenasa o antibiótico); y 89% no utilizaban compresión para el manejo del edema. Conclusión: la mayoría de los participantes no estaba integrada en la Red de Atención a la Salud para el tratamiento de la úlcera, y no recibía asistencia sistematizada ni insumos apropiados.
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Introduction: Anemia is a highly prevalent disorder. Preoperative anemia is associated with higher mortality, more complications, longer hospital stays, and higher healthcare costs. Red blood cell transfusion (RBC) does not improve these outcomes. The World Health Organization recommends implementing Patient Blood Management (PBM) programmes, as they can improve these clinical outcomes, reduce unnecessary RBC transfusions, and save costs. Despite compelling evidence, the implementation of these measures has yet to be effectively achieved. The objective of this study is to conduct a situational analysis to raise awareness about this issue and encourage the implementation of these measures. Methodology: An observational, longitudinal, retrospective cohort study was conducted at a single center. All patients undergoing elective surgery from 01/01/2022 to 01/04/2022 at the Hospital de Clínicas were included. Exclusion criteria: absence of a complete blood count in the three months prior to surgery and refusal to participate in the study. Results: A total of 329 surgeries were analyzed. 52 out of 100 procedures were performed on patients with anemia. A statistically significant association was found between preoperative anemia and receiving RBC transfusion during hospitalization. OR 11.746 (4.518 - 30.540). Anemia and RBC transfusions significantly prolonged hospital stay. Length of hospitalization based on patient condition: No anemia: 10.1 ± 1.1 days, with anemia: 27.2 ± 2.3 days. Value of p < 0.001. Non-transfused: 14.5 ± 1.3 days, transfused: 41.8 ± 4.4 days. Value of p < 0.001. Only 49 (28.6%) of the 171 patients with anemia had iron metabolism assessed before surgery. Among the 140 patients with Hb < 12 g/dL undergoing surgeries with non-insignificant bleeding, only 4 received specific treatment to optimize Hb. A total of 185 units of red blood cells (RBC) were administered during hospitalization. 49 to unstable patients (intraoperative or acute hemorrhage) and 136 to stable patients. From the analysis of the latter group, 42.5% of the patients received 3 or more RBC units. The average pre-transfusion hemoglobin was 7.0 ± 0.1. A statistically significant association was found between receiving RBC units and dying during hospitalization. OR 17.182 (3.360 - 87.872). Conclusiones: A situational analysis was conducted, revealing a high prevalence of preoperative anemia, scarce study and treatment of anemia before surgeries, and an excessive amount of blood transfusions received by some patients. This work establishes the need to implement Patient Blood Management programs to reduce the prevalence of preoperative anemia and improve our transfusion practices. It also sets a comparative framework to evaluate the progress of these measures and indicates possible indicators to assess the benefits of their implementation.
Introdução : A anemia é um distúrbio altamente prevalente. A anemia pré-operatória está associada a maior mortalidade, mais complicações, tempo prolongado de internação e maiores custos de saúde. A transfusão de glóbulos vermelhos (TGV) não melhora esses resultados. A Organização Mundial da Saúde recomenda a implementação de medidas de Gerenciamento de Sangue do Paciente (GSP), pois permitem melhorar esses resultados clínicos, reduzir TGV desnecessárias e economizar custos. Apesar da evidência contundente, a implementação dessas medidas ainda está aquém de ser efetivada. O objetivo deste trabalho é realizar uma análise da situação para conscientizar sobre o problema e incentivar a implementação dessas medidas. Metodologia: Foi realizado um estudo observacional, longitudinal, retrospectivo de coorte histórica, unicêntrico. Foram incluídos todos os pacientes submetidos a cirurgias de coordenação de 01/01/2022 a 01/04/2022 no Hospital de Clínicas. Critérios de exclusão: ausência de hemograma nos três meses anteriores à cirurgia e recusa em participar do estudo. Resultados: Foram analisadas um total de 329 cirurgias. 52 a cada 100 procedimentos foram realizados em pacientes com anemia. Foi encontrada uma associação estatisticamente significativa entre a anemia pré-operatória e a recepção de TGR durante a internação. OR 11,746 (4,518 - 30,540). A anemia e as TGR prolongaram significativamente a internação hospitalar. Dias de internação em função da condição do paciente: Sem anemia: 10,1 ± 1,1 dias, com anemia: 27,2 ± 2,3 dias. Valor p < 0,001. Não transfundidos: 14,5 ± 1,3 dias, transfundidos: 41,8 ± 4,4 dias. Valor p < 0,001. Apenas 49 (28,6%) dos 171 pacientes com anemia tinham metabolismo do ferro antes da cirurgia. Dos 140 pacientes com Hb < 12 mg/dL submetidos a cirurgias com sangramento não insignificante, 4 receberam tratamento específico para otimizar a Hb. Foram administradas um total de 185 unidades de glóbulos vermelhos (UGV) durante a internação. 49 em pacientes instáveis (intraoperatório ou hemorragia aguda) e 136 em pacientes estáveis. Da análise desses últimos, 42,5% dos pacientes receberam 3 ou mais UGV. A hemoglobina pré-transfusional média foi de 7,0 ± 0,1. Foi encontrada uma associação estatisticamente significativa entre receber UGV e falecer durante a internação. OR 17,182 (3,360 - 87,872). Conclusões: Foi realizado uma análise da situação na qual foi observada uma elevada prevalência de anemia pré-operatória, um estudo e tratamento escasso da anemia antes das cirurgias e uma quantidade excessiva de UGV recebidas por alguns pacientes. Este trabalho estabelece a necessidade de implementar programas de Gerenciamento de Sangue do Paciente para reduzir a prevalência de anemia pré-operatória e melhorar nossas práticas transfusionais. Além disso, estabelece um quadro comparativo para avaliar o progresso dessas medidas e aponta possíveis indicadores para avaliar os benefícios de sua implementação.
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Abstract Background Merkel cell polyomavirus (MCPyV), a human polyomavirus that is unequivocally linked to merkel cell carcinoma (MCC), has been found in association with keratinocytes carcinomas (KC), especially basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Nevertheless, there is scarce information about the possible involvement of MCPyV in the development of KC. Objectives To assess the presence of MCPyV DNA and Large-T Antigen (LT-Ag) via Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) in cases of KC, and to correlate its presence with immunohistochemical markers p16, p53, and ki67, tumor type and subtype, sun-exposed location, and epidemiological data. Methods The prevalence of MCPyV DNA, LT-Ag, and immunohistochemical markers p16, p53, and ki67 was assessed by PCR and Immunohistochemistry (IHC) in 127 cases of KC, these results were correlated with tumor type and subtype, sun-exposed location, and epidemiological data. Results The MCPyV DNA was detected in 42.57% (43 of 101) cases by PCR, the LT-Ag was detected in 16.4% (20 of 122) of cases, p16 in 81.5% (97 of 119), p53 in 66.4% (83 of 125), ki67 in 89% (73 of 82). No correlation between MCPyV LT-Ag and DNA confronted with tumor type, subtype, location site, and immunohistochemical markers was found. A single correlation between the MCPyV LT-Ag and cSCC tumors and peri-tumoral lymphocyte cells was noted. Study limitations Further steps need to be taken to better evaluate the MCPyV influence and its possible role in KC carcinogenesis, as the evaluation of the virus genome state, the gene sequence that encodes LT-Ag in the KC tumor cells, and in situ hybridization for viral DNA or RNA in these cells. Conclusions Despite the frequent detection of MCPyV in KC, the data available so far does not support the hypothesis of a causal relationship between them.
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PIWI proteins, traditionally associated with germline development, have recently gained attention for their expression in various cancers, including colorectal cancer. However, the molecular mechanisms underlying their reactivation and impact on cancer initiation and progression remain elusive. Here, we found that PIWIL1 is expressed at relatively high levels in CRC-derived samples and cell lines, where it undergoes a dynamic relocalization to the centrosome during mitosis. Knockdown of PIWIL1 induces G2/M arrest associated with disruption of the mitotic spindle and aberrant metaphase events, highlighting its role in cell cycle progression. We also found that the expression of PIWIL1 is lost during the differentiation of Caco-2 cells into enterocytes and that PIWIL1 is expressed in cells at the base of the intestinal crypts in normal human colon tissue, where intestinal stem cells are known to reside. Thus, it is possible that the presence of PIWIL1 in cancer cells reflects a physiological role of this protein in stem cell maintenance, which would argue in favor of the proposed stem cell origin of CRC. Supporting this view, dedifferentiation of human fibroblasts into induced pluripotent stem cells (iPSCs) involves the reactivation of PIWIL2 expression, another member of the PIWI protein family. Overall, our findings suggest a role of PIWIL1 in mediating cell cycle dynamics, both in colorectal cancer cells and possibly also in intestinal stem cells. In a broader aspect, we provide evidence supporting an involvement of PIWI proteins in somatic stem cell maintenance, thus expanding the known non-gonadal functions of this protein family.
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Proteínas Argonautas , Centrosoma , Neoplasias Colorrectales , Mitosis , Humanos , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Centrosoma/metabolismo , Células CACO-2 , Ciclo Celular , Diferenciación Celular , Línea Celular TumoralRESUMEN
The relationship between bullous pemphigoid (BP) and neoplasms has been debated in the medical literature. Although numerous case reports have described the coexistence of BP with various neoplasms, case-control studies have yielded conflicting results. We present the case of a male patient who developed BP shortly after being diagnosed with mycosis fungoides (MF). He was a 77-year-old man with a history of type 2 diabetes mellitus and hypertension who was diagnosed with MF. Subsequently, he developed blisters after sun exposure, and was diagnosed with BP through histopathology and direct immunofluorescence. The patient was treated with prednisone and methotrexate, with favorable evolution without recurrence of MF or appearance of new blisters. The association between cutaneous T-cell lymphoma and autoimmune blistering disease is rare, although similar cases have been reported, some associated with phototherapy. In this case, the onset of BP after sun exposure suggests a potential connection. The coexistence of BP and MF remains controversial, and this case highlights the importance of considering autoimmune blistering diseases in patients with oncohematological neoplasms.
La relación entre el penfigoide ampollar (PA) y las neoplasias ha sido objeto de debate en la literatura médica. Aunque numerosos informes de casos han descrito la coexistencia del PA con diversas neoplasias, estudios de casos y controles han arrojado resultados contradictorios. Presentamos el caso de un paciente masculino que desarrolló un PA poco después de ser diagnosticado con una micosis fungoide (MF). Se trata de un hombre de 77 años con antecedentes de diabetes mellitus tipo 2 e hipertensión arterial que fue diagnosticado con MF. Posteriormente, desarrolló ampollas después de una exposición solar, siendo diagnosticado con PA mediante histopatología e inmunofluorescencia directa. El paciente fue tratado con meprednisona y metotrexato, evolucionando favorablemente sin recurrencia de MF ni aparición de nuevas ampollas. La asociación entre un linfoma cutáneo de células T y una enfermedad ampollar autoinmune es rara, aunque han sido reportados casos similares, algunos asociados con fototerapia. En este caso la aparición del PA después de la exposición solar sugiere una conexión potencial. La coexistencia entre PA y MF sigue siendo controvertida, y este caso destaca la importancia de considerar enfermedades ampollares autoinmunes en pacientes con neoplasias oncohematológicas.
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Micosis Fungoide , Penfigoide Ampolloso , Neoplasias Cutáneas , Humanos , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/etiología , Micosis Fungoide/complicaciones , Micosis Fungoide/patología , Micosis Fungoide/diagnóstico , Masculino , Anciano , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Prednisona/uso terapéutico , Metotrexato/uso terapéuticoRESUMEN
INTRODUCTION: Fat graft (FG) absorption rate varies from 20 to 80% in two years. Recently, several bioengineering techniques were applied to improve FG retention rate. Numerous studies investigated the use of adipocyte-derived stem cells (ASC) as FG enrichment. However, ASC production is costly, complex, and time-consuming. In contrast, Nanofat, a combination of lipids, stem cells and growth factors, offers a faster, simpler, and more cost-effective alternative for FG enrichment. OBJECTIVE: This study aims to compare the effects of ASC with those of Nanofat, as a viable option in FG enrichment. MATERIAL AND METHODS: Animals were allocated in three groups: Control group (1 mL fat), ASC group (1 mL fat +1x106 ASC), and NnF group (1 mL of fat + 0.3mL NnF). These groups were subdivided in three subgroups (4, 8, and 12 weeks, n = 6/group). We performed ultrasound and macroscopic measurements for FG volume, histology and expression of healing and inflammation genes. RESULTS: At week 12, ASC and NnF groups showed a higher retention of FG when compared to the Control group (51%, 46%, 12% respectively, p < 0.01). Fibrosis was similar in ASC and Nanofat groups. The Nanofat group showed a higher vascular density then the Control group (p < 0.05). Il-10 gene expression was higher, and Mmp9 was lower in the Nanofat group when compared to the ASC and Control groups. CONCLUSION: This study indicates that enriching FG with both ASC and Nanofat led to an increased retention rate of the FG, suggesting that Nanofat might be a promising alternative for FG enrichment. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of combining pemetrexed and platinum with or without pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC). METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web Of Science databases was conducted to identify studies comparing pemetrexed and platinum with or without pembrolizumab in advanced NSCLC. Raw data were extracted from eligible studies to calculate Hazard Ratios (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), as well as rates of adverse events of all grades and those of Grade 3 or higher. RESULTS: Eight studies with 1639 patients occurred advanced NSCLC included. The group receiving pembrolizumab in combination with pemetrexed and platinum showed significant benefits in terms of OS (HR 0.63; 95% CI 0.54-0.73; p < 0.00001) and PFS (HR:0.64; 95% CI 0.48-0.85; p = 0.002) compared to the group receiving pemetrexed and platinum alone. However, this benefit was accompanied by a higher incidence of Grade 3 or higher adverse events (OR: 1.55; 95% CI 1.24-1.95; p = 0.0001). CONCLUSION: The combination of pemetrexed and platinum with pembrolizumab is recommended as a first-line treatment option for advanced NSCLC due to its significant efficacy benefits. However, the increased risk of Grade 3 or higher adverse events suggests the need for careful consideration and assessment when considering this regimen for second-line or subsequent therapy.
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Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. OBJECTIVE: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. METHOD: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. RESULTS: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. CONCLUSIONS: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Cordón Umbilical , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Cordón Umbilical/citología , Ratas , Humanos , Proliferación Celular/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Ciclo Celular/efectos de los fármacos , Daño del ADNRESUMEN
Mushroom ß-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some ß-D-glucans may exhibit direct antitumoral effects. It was previously observed that a ß-(1â6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10-1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the ß-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.
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Agaricus , Antineoplásicos , Apoptosis , Neoplasias de la Mama , Supervivencia Celular , Estrés Oxidativo , Receptores de Estrógenos , Agaricus/química , Humanos , Células MCF-7 , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Supervivencia Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , beta-Glucanos/farmacología , beta-Glucanos/químicaRESUMEN
Cauliflower (Brassica oleraceae L. var. Botrytis Linnaeus) has various health benefits due to its rich bioactive compound content. However, this fresh vegetable faces challenges related to its perishability and short shelf life. This study explores the effect of five drying methods, namely vacuum drying (VD), convective drying (CD), infrared drying (IRD), low-temperature vacuum drying (LTVD) and vacuum freeze-drying (VFD), on the bioactive compounds and health-promoting properties of cauliflower. Analyses of amino acids, hydroxycinnamic acid and its derivatives, glucosinolates, and isothiocyanates, as well as evaluations of their anti-inflammatory, antiproliferative, and neuroprotective properties, were conducted based on these five drying methods. The results revealed that samples treated with VFD and IRD had a higher content of amino acids involved in GSL anabolism. Moreover, VFD samples retained hydroxycinnamic acid derivatives and glucosinolates to a greater extent than other methods. Nonetheless, the CD and VD samples exhibited higher antiproliferative and neuroprotective effects, which were correlated with their high sulforaphane content. Overall, considering the retention of most bioactive compounds from cauliflower and the topical inflammation amelioration induced in mice, VFD emerges as a more satisfactory option.
RESUMEN
BACKGROUND: Skin cancer is the most common cancer in human beings. Ultrasound is a powerful and non-invasive imaging technique that has expanded its use in dermatology, including in the skin cancer field. The full range of critical anatomical information provided by ultrasound cannot be deduced from a naked eye examination, palpation, or other imaging techniques such as dermoscopy, confocal microscopy, magnetic resonance imaging, or PET-CT (Positron Emission Tomography-Computed Tomography). METHODS: This review practically analyzes the main ultrasonographic features of the most common types of skin cancers and the performance of the locoregional staging according to the literature, which is illustrated by state-of-the-art clinical and ultrasonographic correlations. RESULTS: The most common types of skin cancer show recognizable ultrasonographic patterns. CONCLUSIONS: Among the current radiological imaging techniques, ultrasound has the highest axial spatial resolution. Compared to other imaging techniques used in dermatology, it shows the great advantage of penetrating the soft tissues thoroughly, which allows us to detect and identify the most common skin types of skin cancer, including both the primary tumor and its locoregional metastases.
RESUMEN
PURPOSE: Evaluate the immunohistochemical expression of the ING3 in actinic cheilitis and squamous cell carcinoma of the lower lip. METHODS: Forty-five specimens of actinic cheilitis and 48 specimens of squamous cell carcinoma of the lower lip were submitted to immunohistochemical detection of ING3. The protein expression in different cellular sublocations was compared between the two groups, and associations with the clinicopathological variables were analyzed. A significance level of 5% was adopted for all tests. RESULTS: Deaths were significantly more frequent in tumors with a high histopathological risk score (p < 0.05). In actinic cheilitis, significant differences were found in the nucleus-cytoplasmic expression of ING3 and expression restricted to the cytoplasm with binary histopathological grading (p < 0.05). In squamous cell carcinoma of the lower lip, there was no statistically significant difference when comparing ING3 expressions with clinical and morphological parameters (p > 0.05). Nucleo-cytoplasmic ING3 expression was significantly lower in squamous cell carcinoma of the lower lip when compared to actinic cheilitis (p < 0.05) and the expression restricted to the cytoplasm was significantly higher in squamous cell carcinoma of the lower lip (p < 0.05). CONCLUSION: The results of this study suggest that there is a marked decrease in the nuclear expression of ING3 as malignant progression occurs, indicating an impaired tumor suppressor function of this protein in actinic cheilitis and squamous cell carcinoma of the lower lip.