Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Inhibition of Gelatinases by Vegetable Extracts of the Species Tapirira guianensis (Stick Pigeon).

Tapirira guianensis (Stick pigeon), a widely-used herbal medicine, has been reported to possess various biological activities. The aim of this study was the phytochemical analysis of the fractions of extracts of T. guianensis and the investigation of the action of these extracts on the activity of gelatinases using zymography. Matrix metalloproteinases (gelatinases) have prognostic influences in human cancers, where higher expressions of these enzymes are associated with increased aggressiveness and biological behavior of tumors. Many natural products have been tested on several stages of carcinogenesis to demonstrate their effectiveness in the inhibition or activation of molecules that are important for tumor progression. This study identified the fractions obtained from the crude extract of T. guianensis (Stick pigeon), which efficiently inhibited gelatinases.

Criopreservaçäo do sêmen testicular do teleósteo piau-açu Leporimus macrocephalus / Testicular sperm cryopreservation of the teleost 'piau-açu' Leporinus macrocephalus

Avaliaram-se metodologias de criopreservaçäo para o sêmen do piau-açu Leporinus macrocephalus (Teleostei, Anostomidae). O volume de sêmen coletado diretamente dos testículos de seis peixes (446,7±165,1g de peso corporal) foi de 0,4±0,2 ml. Testou-se a toxicidade dos crioprotetores dimetilsulfóxido (DMSO), dimetilacetamida, propilenoglicol, etilenoglicol e metanol nas concentraçöes de 5 por cento, 10 por cento e 15 por cento. DMSO, dimetilacetamida e propilenoglicol foram os menos tóxicos e, por isso, utilizados na criopreservaçäo do sêmen. Para este teste, o sêmen foi diluído 1:8 (v:v) em soluçöes de cada crioprotetor(8,9 por cento, concentraçäo final) às quais adicionaram-se gema de ovo de galinha (8,9 por cento, concentraçäo final), glicose (5 por cento) e água destilada (75 por cento). A mistura foi entäo envasada em palhetas de 5ml de capacidade e imediatamente colocada em botijäo de vapor de nitrogênio líquido. A taxa de motilidade espermática pós-descongelamento mais alta (40,8± 13,6 por cento) foi obtida com sêmen criopreservado em diluente contendo DMSO e ativado em soluçäo de NaHCO3 119mM. A taxa de fertilizaçäo, correspondente a 84,3±9,4 por cento do controle, foi obtida com ovócitos de piau-açu fertilizados com sêmen congelado em soluçäo de DMSO (8 por cento, concentraçäo final)