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.

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.

Generalizability of machine learning models and empirical equations for the estimation of reference evapotranspiration from temperature in a semiarid region.

The Penman-Monteith equation is recommended for the estimation of reference evapotranspiration (ETo). However, it requires meteorological data that are commonly unavailable. Thus, this study evaluates artificial neural network (ANN), multivariate adaptive regression splines (MARS), and the original and calibrated Hargreaves-Samani (HS) and Penman-Monteith temperature (PMT) equations for the estimation of daily ETo using temperature. Two scenarios were considered: (i) local, models were calibrated/developed and evaluated using data from individual weather stations; (ii) regional, models were calibrated/developed using pooled data from several stations and evaluated independently in each one. Local models were also evaluated outside the calibration/training station. Data from 9 stations were used. The original PMT outperformed the original HS, but after local or regional calibrations, they performed similarly. The locally calibrated equations and the local machine learning models exhibited higher performances than their regional versions. However, the regional models had higher generalization capacity, with a more stable performance between stations. The machine learning models performed better than the equations evaluated. When comparing the ANN models with the HS equation, mean RMSE reduced from 0.96 to 0.87 and from 0.84 to 0.73, in regional and local scenarios, respectively. ANN and MARS performed similarly, with a slight advantage for ANN.

Dermoid and epidermoid cysts of the oral cavity: a 48-year retrospective study with focus on clinical and morphological features and review of main topics.

BACKGROUND: Dermoid and epidermoid cysts are slow-growing, benign developmental cysts that arise from ectodermal tissue and can occur anywhere in the body. Less than 7% of these cysts involve the head and neck region, with only 1.6% of cases presenting in the oral cavity. To evaluate the clinical and histopathological features of dermoid (DCs) and epidermoid (ECs) cysts stored in the archives of a referred Oral Pathology Service over a 48-year-period, and to review current concepts about these cysts. MATERIAL AND METHODS: All DCs and ECs were reviewed, and clinical data were obtained from the patient records. Fourteen cases of DCs and thirteen cases of ECs were re-evaluated microscopically by 2 oral pathologists. RESULTS: Among 15.387 cases, 14 (0.09%) had a histopathological diagnosis of DCs and 13 (0.08%) of ECs. For DCs, ten (71.4%) patients were women, with the mean age of 37.2 years. All DCs were lined by a stratified squamous epithelium (100%), with gut and respiratory epithelium observed in 1 (7.1%) and 2 (14.3%) cases, respectively. Chronic inflammatory cells, melanin, multinucleated giant cell reaction, and Pacini bodies were also observed. For ECs, eight (61.5%) cases were in women, and the mean age was 38.2 years. All ECs were lined by a stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, and adipose tissue were observed in the fibrous capsule. CONCLUSION: Our results suggest that stratified squamous epithelium is the predominant epithelial lining of these cystic lesions. Also, we may find some unusual findings in DCs, such as Pacini bodies.

Composição nutricional e valores energéticos determinados com frangos de corte de coprodutos do processamento do etanol de milho / Nutritional composition and energy values determined with broilers of co-products from the processing of corn ethanol

It was determined by the total collection of excreta method, with broilers from 22 to 32 days of age, the coefficients of apparent metabolism of dry matter, crude protein and crude energy and apparent metabolizable energy corrected for zero nitrogen balance (AMEn) of the ethanol co-products of corn: acid oil and dried distillery grains with soluble (DDGS). The DDGS and corn acid oil presented nutritional metabolization coefficients ranging from 43 to 83% and AMEn equal 2393.5 and 7859.2kcal/kg respectively, and may be food alternatives to soybean meal and soybean oil.(AU)

Histopathological grading systems and their relationship with clinical parameters in lower lip squamous cell carcinoma.

The objective of this study was to evaluate the histopathological grade of malignancy in a series of lower lip squamous cell carcinomas (LLSCCs) using three histopathological grading systems (invasive front grading system, World Health Organization (WHO) grading system, and histological risk assessment), and to correlate this with clinical parameters (tumour size/extent, regional lymph node metastasis, and clinical stage). Haematoxylin-eosin-stained histological sections obtained from 59 cases of LLSCC were analyzed by light microscopy. Grading of the invasive tumour front showed a significant association between low grade of malignancy and the absence of regional lymph node metastasis (P=0.030) and initial clinical stage (P=0.043). No significant associations were observed between the clinical parameters analyzed and the WHO system (P>0.05). Using the risk assessment, a highly significant association was observed between the risk score and regional lymph node metastasis (P=0.004) and clinical stage (P=0.002). In addition, the lymphocytic infiltrate was significantly associated with regional lymph node metastasis (P=0.017) and clinical stage (P=0.040). The results of the present study suggest that, among the histopathological grading systems evaluated, the histological risk assessment is the best option to predict the biological behaviour of LLSCCs.

Apoptosis, cell proliferation and vitellogenesis during the folliculogenesis and follicular growth in teleost fish.

Aiming to better understand folliculogenesis, this study evaluated cell death and proliferation of ovarian cells, besides cathepsin-D expression in Prochilodus argenteus captured in two sites of the São Francisco River downstream from the Três Marias Dam, Brazil. In the site immediately following the Dam (S1), low levels of dissolved oxygen were registered in the rainy period. The water temperature was higher in the São Francisco River immediately after the confluence with the Abaeté River (S2), regardless of the period. In S1, the ovaries showed smaller oocytes, high caspase-3 enzymatic activity and apoptosis, lower cells in proliferation and GSI, as well as a lesser quantity of cathepsin-D when compared to females captured from S2. Regarding relative frequency of ovarian structures, in the dry period, only oogonia and perinucleolar oocytes were found in fish ovaries from both sites. On the other hand, in the rainy period, the relative frequency of oogonia and perinucleolar oocytes decreased and the vitellogenic oocytes increased in S2. Postovulatory follicles were observed only in S2, whereas atretic follicles occurred at a higher frequency in S1. Our results showed that apoptosis, cell proliferation and cathepsina-D evaluation can be used as biomarkers of environmental impact.

Ovarian follicular atresia is mediated by heterophagy, autophagy, and apoptosis in Prochilodus argenteus and Leporinus taeniatus (Teleostei: Characiformes).

We investigated apoptosis, cell proliferation antigen (PCNA), and heat shock protein (HSP70) during ovarian follicular atresia in two freshwater teleost species from the São Francisco River basin, Brazil: curimatã-pacu, Prochilodus argenteus and piau-jejo, Leporinus taeniatus. Fishes were maintained in captivity after the reproductive period and ovarian regression was assessed by gonadosomatic index for three stages: early, advanced, and late regression. Follicular atresia was analysed by light and transmission electron microscopy, as well as by TUNEL and immunohistochemistry for HSP70 and PCNA. During early regression, atretic follicles exhibited zona pellucida breakdown, yolk degeneration, and hypertrophied follicular cells (e.g., granulosa in mammals). Intense heterophagy to engulf the yolk, and autophagy were detected in the follicular cells during advanced and late atresia. The TUNEL assay detected DNA fragmentation, mainly in late follicular atresia. The apoptosis rate of the follicular cells increased up to 10% during follicular atresia in both species and was negatively correlated with follicular area. Immunohistochemistry reaction for HSP70 stained the follicular cells strongly during advanced atresia, when they are intensively involved in yolk engulfment, whereas the reaction for PCNA labelled theca cells. We inferred that heterophagy, autophagy, and apoptosis contributed to follicular atresia in teleost ovaries, thereby achieving a more efficient removal of the degenerating oocyte and dying follicular cells. Additionally, HSP70 may protect the follicular cells before apoptosis when they are involved in yolk engulfment, and cell proliferation in the theca contributed to ovarian remodelling.

Relationship among follicular apoptosis, integrin beta1 and collagen type IV during early ovarian regression in the teleost Prochilodus argenteus after induced spawning.

Early ovarian regression was analyzed in the neotropical freshwater teleost, curimatã-pacu (Prochilodus argenteus), in order to evaluate follicular apoptosis, basement membrane morphology, and integrin beta1 and collagen type IV immunostainning in postovulatory follicles. Mature females were induced to spawn by using carp pituitary extract for study of ovarian regression up to 5 days post-spawning. Morphometric analyses showed that the postovulatory follicle area decreased progressively after spawning and was coupled to the gonadosomatic index (r=0.92). During ovarian regression, follicular cells detached from the neighboring cells and basement membrane and then died by apoptosis. The follicular basement membrane became thicker and diffuse and was breached during regression of the postovulatory follicles. Follicular apoptosis was detected by TUNEL, histology, and electron microscopy. The ladder pattern of apoptotic DNA was revealed by agarose gel electrophoresis. The apoptotic index for the follicular cells increased until 3 days post-spawning and decreased thereafter. Immunohistochemistry reactions detected caspase 3, integrin beta1, and collagen type IV in the follicular layer of the postovulatory follicles. Labeling for integrin beta1 and collagen type IV decreased significantly, whereas a peak in cell death occurred 3 days post-spawning. At 4-5 days post-spawning, the connective theca was more thickened and vascularized. Simultaneously, granulocytes migrated toward the follicular lumen. Thus, follicular apoptosis contributes to early ovarian regression in P. argenteus. Additionally, our findings suggest integrin beta1 and collagen type IV as possible survival factors for follicular cells in teleost ovary.