Ozonioterapia como opção ao tratamento de lesões cutâneas em humanos: revisão integrativa da literatura / Ozone therapy as an option for the treatment of skin lesions in humans: an integrative literature review / La ozonoterapia como opción para el tratamiento de lesiones cutáneas en humanos: revisión bibliográfica integradora

Este trabalho teve como objetivo realizar uma revisão integrativa sobre a Ozonioterapia como prática complementar no tratamento de lesões em seres humanos. Efetuou-se busca sistematizada nos portais: Biblioteca virtual em saúde (BVS), Biblioteca virtual em saúde de medicinas tradicionais complementares e integrativas (BVS MTCI) e Business source complete (EBSCO) nas seguintes bases de dados: Literatura latino-americana e do caribe em ciências da saúde (LILACS), Base de dados de Enfermagem (BDENF) e Medical literature analysis and retrievel system Online (MEDLINE), com cruzamento dos descritores: ozônio; ferimentos; lesões; cicatrização de feridas. Após os critérios de inclusão serem aplicados, observou-se que dez artigos atingiram todos os critérios previamente definidos. Os estudos apontam que a Ozonioterapia apresenta resultados positivos como opção na terapêutica complementar de lesões. Porém, é um recurso terapêutico com baixa adesão. Faz se necessário maior empenho cientifico sobre a temática. PALAVRAS-CHAVE: Ozônio; Ferimentos; Lesões; Cicatrização de feridas.

Currently, there are several treatments as well as ozone therapy that aim to improve wounds. This work aimed to carry out an integrative review on Ozone Therapy as a complementary practice in the treatment of injuries in humans. A systematic search was conducted on the portals: Virtual Health Library (VHL), Virtual Health Library of Complementary and Integrative Traditional Medicines (VHL MTCI) and Business Source Complete (EBSCO) in the following databases: Latin American and Caribbean Literature in Health Science (LILACS) , Nursing Database (BDENF) and Online Medical Literature Review and Retrieval System (MEDLINE), by crossing descriptors: Ozone, Wounds and Injuries, Healing injuries. After the inclusion criteria were applied, it was observed that ten articles reached all the criteria previously defined. The studies indicate that Ozone therapy presents positive results as a complementary therapy option on wounds. However, it is a therapeutical resource with low adherence. It is necessary a greater scientific commitment on the theme.

Este trabajo tuvo como objetivo realizar una revisión integradora sobre la ozonoterapia como práctica complementaria en el tratamiento de lesiones en humanos. Se realizó una búsqueda sistemática en los siguientes portales: Biblioteca Virtual de Salud (BVS), Biblioteca Virtual de Salud de Medicinas Tradicionales, Complementarias e Integrativas (BVS MTCI) y Business Source Complete (EBSCO) en las siguientes bases de datos: Latin American and Caribbean Health Sciences Literature (LILACS), Nursing Database (BDENF) y Medical Literature Analysis and Retrieval System Online (MEDLINE), utilizando las palabras clave: ozono; heridas; lesiones; curación de heridas. Una vez aplicados los criterios de inclusión, se observó que diez artículos cumplían todos los criterios previamente definidos. Los estudios demostraron que la ozonoterapia tiene resultados positivos como opción terapéutica complementaria para las lesiones. Sin embargo, es un recurso terapéutico con un bajo cumplimiento. Es necesario un mayor esfuerzo científico sobre el tema.

Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells.

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.

Cyclopalladated compounds containing 2,6-lutidine: Synthesis, spectral and biological studies.

Bridge splitting reactions between [Pd(C2,N-dmba)(µ-X)]2 (dmba = N,N-dimethylbenzylamine; X = Cl, I, N3, NCO) and 2,6-lutidine (lut) in the 1:2 molar ratio at room temperature afforded cyclopalladated compounds of general formulae [Pd(C2,N-dmba)(X)(lut)] {X = Cl- (1), I-(2), NNN-(3), NCO-(4)}, which were characterized by elemental analyses and infrared (IR), 1H NMR spectroscopy. The molecular structures of all synthesized palladacycles have been solved by single-crystal X-ray crystallography. The cytotoxicity of the cyclopalladated compounds has been evaluated against a panel of murine {mammary carcinoma (4T1) and melanoma (B16F10-Nex2)} and human {melanoma (A2058, SK-MEL-110 and SK-MEL-5) tumor cell lines. All complexes were about 10 to 100-fold more active than cisplatin, depending on the tested tumor cell line. For comparison purposes, the cytotoxic effects of 1-4 towards human lung fibroblasts (MRC-5) have also been tested. The late apoptosis-inducing properties of 1-4 compounds in SK-MEL-5 cells were verified 24 h incubation using annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide (PI). The binding properties of the model compound 1 on human serum albumin (HSA) and calf thymus DNA (ct-DNA) have been studied using circular dichroism and fluorescence spectroscopy. Docking simulations have been carried out to gain more information about the interaction of the palladacycle and HSA. The ability of compounds 1-4 to inhibit the activity of cathepsin B and L has also been investigated in this work.

Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development.

OBJECTIVE: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root. This study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root (CEAA) on breast cancer. METHODS: The cytotoxicity of CEAA against breast adenocarcinoma cells (4T1 and MCF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide (PI) and annexin V/PI staining. Cytosolic calcium mobilization was evaluated in cells staining with FURA-4NW. Immunoblotting was used to determine the effect of CEAA on anti- and pro-apoptotic proteins (Bcl-2 and Bax, respectively). The 4T1 cell-challenged mice were used for in vivo assay. RESULTS: Using ultra-high-performance liquid chromatography-mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the CEAA evaluated in this study (73 µg/mL). The CEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4T1 cells with the CEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the CEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in CEAA-treated MCF7 cells. Gavage administration of the CEAA (500 mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated animals. CONCLUSION: Altogether, our data show the antitumor potential of the CEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the CEAA in breast cancer therapy.

In vitro cytotoxicity of chemical preservatives on human fibroblast cells

Preservatives are widely used substances that are commonly added to various cosmetic and pharmaceutical products to prevent or inhibit microbial growth. In this study, we compared the in vitro cytotoxicity of different types of currently used preservatives, including methylparaben, imidazolidinyl urea (IMU), and sodium benzoate, using the human newborn fibroblast cell line CCD1072Sk. Of the tested preservatives, only IMU induced a reduction in cell viability, as shown using the MTT assay and propidium iodide staining (IMU>methylparaben>sodium benzoate). IMU was shown to promote homeostatic alterations potentially related to the initiation of programed cell death, such as decreased mitochondrial membrane potential and caspase-3 activation, in the treated cells. Methylparaben and sodium benzoate were shown to have a very low cytotoxic activity. Taken together, our results suggest that IMU induces programed cell death in human fibroblasts by a canonical intrinsic pathway via mitochondrial perturbation and subsequent release of proapoptotic factors

Cafestol, a diterpene molecule found in coffee, induces leukemia cell death.

To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol.

Avaliação in vitro da atividade do ácido hialurônico de baixo peso molecular sobre a proliferação de fibroblástos dérmicos humanos / In vitro evaluation of acid activity hyaluronic acid of low molecular weight on proliferation of human dermal fibroblasts

O ácido hialurônico de baixo peso molecular (AH) é proposto como agente que atua nas três fases da reparação tecidual. O objetivo deste trabalho foi avaliar se o AH é capaz de induzir proliferação celular de fibroblastos dérmicos humanos. Esses efeitos foram avaliados empregando-se as técnicas de azul de tripano e de brometo de [3-(4,5-dimetiltiazol-2yl)-2,5-difenil tetrazolium] (MTT),seguida de análise do ciclo celular, produção de colágeno e modelo de wound healing (WH). Após tratamento com AH, foi verificado aumento significativo na proliferação das células e nas fases S-G2-M do ciclo celular. Quando submetido ao teste de WH, a exposição a 0,2% de AH promoveu redução significativa da área da lesão, com taxas de migração celular de 74%. Os resultados confirmam a capacidade do AH em aumentar a proliferação de fibroblastos, o que é relevante para a fase proliferativa da cicatrização.

The biphosphinic paladacycle complex induces melanoma cell death through lysosomal-mitochondrial axis modulation and impaired autophagy.

Recently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal-mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria. Mitochondrial hyperpolarization, followed by membrane potential dissipation and cleavage of caspase-3, also resulted in cell death after 24 h of incubation. We also found that BPC11-mediated LC3II formation and increased p62 protein levels, suggesting blocked autophagy, probably due to LMP. Interestingly, the treatment of Tm5 and 4C11(-) cells with 3-methyladenine (3-MA), an inhibitor of the initial stage of autophagy, potentiated the effects of BPC11. We conclude that BPC11 is an anti-melanoma agent and that autophagy may be acting as a mechanism of melanoma cells resistance. Also, these data highlight the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties.