RESUMO
Glioblastoma (GBM) is the most common primary brain cancer in adults. Despite the remarkable advancements in recent years in the realm of cancer diagnosis and therapy, regrettably, GBM remains the most lethal form of brain cancer. In this view, the fascinating area of nanotechnology has emerged as an innovative strategy for developing novel nanomaterials for cancer nanomedicine, such as artificial enzymes, termed nanozymes, with intrinsic enzyme-like activities. Therefore, this study reports for the first time the design, synthesis, and extensive characterization of innovative colloidal nanostructures made of cobalt-doped iron oxide nanoparticles chemically stabilized by a carboxymethylcellulose capping ligand (i.e., Co-MION), creating a peroxidase-like (POD) nanozyme for biocatalytically killing GBM cancer cells. These nanoconjugates were produced using a strictly green aqueous process under mild conditions to create non-toxic bioengineered nanotherapeutics against GBM cells. The nanozyme (Co-MION) showed a magnetite inorganic crystalline core with a uniform spherical morphology (diameter, 2R = 6-7 nm) stabilized by the CMC biopolymer, producing a hydrodynamic diameter (HD) of 41-52 nm and a negatively charged surface (ZP~-50 mV). Thus, we created supramolecular water-dispersible colloidal nanostructures composed of an inorganic core (Cox-MION) and a surrounding biopolymer shell (CMC). The nanozymes confirmed the cytotoxicity evaluated by an MTT bioassay using a 2D culture in vitro of U87 brain cancer cells, which was concentration-dependent and boosted by increasing the cobalt-doping content in the nanosystems. Additionally, the results confirmed that the lethality of U87 brain cancer cells was predominantly caused by the production of toxic cell-damaging reactive oxygen species (ROS) through the in situ generation of hydroxyl radicals (·OH) by the peroxidase-like activity displayed by nanozymes. Thus, the nanozymes induced apoptosis (i.e., programmed cell death) and ferroptosis (i.e., lipid peroxidation) pathways by intracellular biocatalytic enzyme-like activity. More importantly, based on the 3D spheroids model, these nanozymes inhibited tumor growth and remarkably reduced the malignant tumor volume after the nanotherapeutic treatment (ΔV~40%). The kinetics of the anticancer activity of these novel nanotherapeutic agents decreased with the time of incubation of the GBM 3D models, indicating a similar trend commonly observed in tumor microenvironments (TMEs). Furthermore, the results demonstrated that the 2D in vitro model overestimated the relative efficiency of the anticancer agents (i.e., nanozymes and the DOX drug) compared to the 3D spheroid models. These findings are notable as they evidenced that the 3D spheroid model resembles more precisely the TME of "real" brain cancer tumors in patients than 2D cell cultures. Thus, based on our groundwork, 3D tumor spheroid models might be able to offer transitional systems between conventional 2D cell cultures and complex biological in vivo models for evaluating anticancer agents more precisely. These nanotherapeutics offer a wide avenue of opportunities to develop innovative nanomedicines for fighting against cancerous tumors and reducing the frequency of severe side effects in conventionally applied chemotherapy-based treatments.
RESUMO
Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.
RESUMO
Objetivo:identificar os efeitos do método de ventosaterapia no alívio da dor cervical em costureiras de uma confecção do segmento vestuário jeans, na região carbonífera do sul catarinense. Método: trata-se de um estudo quantitativo e longitudinal, realizado no segundo semestre de 2019, com a utilização da ventosaterapia durante oito semanas consecutivas em costureiras de uma empresa da linha têxtil no ramo do jeans, entre 40 e 50 anos, que apresentam cervicalgia. Foi utilizado a escala visual analógica para avaliação da dor.Resultados: aamostra foi composta por mulheres com média de 44,75 ± 3,58 anos, que 100% relataram dores antes da ventosaterapia, sendo 75% na cervical e 37,5% sentia essas dores diariamente. Após ventosaterapia, 50% não apresentou dores, 87,5% relatou não atrapalhar nas atividades diárias. Conclusão: foi observado a redução significativa na dor das costureiras, após utilização de terapia com ventosas.
Objective: to identify the effects of the cupping therapy method in the relief of cervical pain in seamstresses of a clothing industry in the jeans industry, in the carboniferous region of southern Santa Catarina. Method: a quantitative and longitudinal study, carried out in the second semester of 2019, with the use of cupping therapy for eight consecutive weeks in seamstresses of a textile company in the jeans industry, between 40 and 50 years old, who have neck pain. The visual analogue scale was used to assess pain. Results: the sample consisted of women with an average of 44.75 ± 3.58 years, of which 100% reported pain before cupping therapy, 75% in the cervical and 37.5% experienced these pains daily. After cupping therapy, 50% had no pain, 87.5% reported no disturbance on their daily activities. Conclusion: a significant reduction in the pain of the seamstresses was observed, after the use of cupping therapy.
Objetivo: Identificar los efectos dela terapia comventosaen el alivio del dolor de cuello en costureras de una confección en el segmento de ropa de mezclilla, en la región carbonífera del sur de Santa Catarina.Método: se trata de un estudio cuantitativo y longitudinal, realizado en el segundo semestre de 2019, con el uso de la eólica durante ocho semanas consecutivas en costureras de una empresa de línea textil de la industria del jeans, de entre 40 y 50 años, que presentan dolor de cuello. La escala analógica visual se utilizó para evaluar el dolor. Resultados: la muestra estuvo conformada por mujeres con un promedio de 44,75 ± 3,58 años, que el 100% refirió dolor antes de la eólica, el 75% en la cervical y el 37,5% sintió estos dolores diariamente. Después de la terapia de viento, el50% no tuvo dolor, el 87,5% informó que no le molestaban las actividades diarias. Conclusión: se observó una reducción significativa del dolor de las costureras, luego del uso de la terapia con ventosa.
