Lobe-specific responses of TRAMP mice dorsolateral prostate following celecoxib and nintedanib therapy.

Delayed cancer progression in the ventral prostate of the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model has been previously reported upon celecoxib and nintedanib co-administration. Herein, we sought to further investigate the effects of these drugs association in some of their direct molecular targets (COX-2, VEGF and VEGFR-2) and in reactive stroma markers (TGF-ß, αSMA, vimentin and pro-collagen 1) in the dorsolateral prostate, looking for lobe-specific responses. Male TRAMP mice were treated with celecoxib (10 mg/Kg, i.o.) and/or nintedanib (15 mg/Kg, i.o.) for 6 weeks and prostate was harvested for morphological and protein expression analyses. Results showed that combined therapy resulted in unique antitumor effects in dorsolateral prostate, especially due to the respective stromal or epithelial antiproliferative actions of these drugs, which altogether led to a complete inversion in high-grade (HGPIN) versus low-grade (LGPIN) premalignant lesion incidences in relation to controls. At the molecular level, this duality in drug action was paralleled by the differential down/upregulation of TGF-ß signaling by celecoxib/nintedanib, thus leading to associated changes in stroma composition towards regression or quiescence, respectively. Additionally, combined therapy was able to promote decreased expression of inflammatory (COX-2) and angiogenesis (VEGF/VEGFR-2) mediators. Overall, celecoxib and nintedanib association provided enhanced antitumor effects in TRAMP dorsolateral as compared to former registers in ventral prostate, thus demonstrating lobe-specific responses of this combined chemoprevention approach. Among these responses, we highlight the ability in promoting TGF-ß signaling and its associated stromal maturation/stabilization, thus yielding a more quiescent stromal milieu and resulting in greater epithelial proliferation impairment.

Brazilian Berry Extract Differentially Induces Inflammatory and Immune Responses in Androgen Dependent and Independent Prostate Cancer Cells.

Jaboticaba is a Brazilian berry, which is rich in fibers and bioactive compounds and shows high antioxidant and antiproliferative activities. Prostate cancer (PCa) is the second most common type of cancer among men and its progression is influenced by androgens and inflammation. Previous studies reported the ability of the jaboticaba to modulate pathways involved in prostate diseases. The main objective of this study was to provide significant data about molecular targets of the jaboticaba peel extract (JPE) and its mechanisms of action in PCa cell lines with different androgenic status (LNCaP and PC-3). The results showed that JPE was able to decrease cell viability in both cell lines. LNCaP showed more sensitivity to JPE exposure, indicating the efficacy of the JPE treatment in terms of androgen responsiveness. JPE showed a distinct hormone dependent effect on the NF-κB signaling, with reduced NF-κB levels for LNCaP and increased NF-κB levels in PC-3 cells. Mechanisms related to cell death by apoptosis were stimulated after the JPE treatment, modulating B-cell lymphoma 2 and BAX for LNCaP and PC-3. Particularly for PC-3, the JPE treatment resulted in cytokine-cytokine receptor interaction activation mostly by up regulating pro-inflammatory, pro-angiogenic, immunostimulatory and immunosuppressive genes. Also, a set of genes related to angiogenesis and metastasis were down-regulated by JPE. In conclusion, JPE exerted an antitumor effect on PCa for both cell lines which can be enhanced if androgenic reliance is considered.

Gut microbiota modulation by jabuticaba peel and its effect on glucose metabolism via inflammatory signaling.

Jabuticaba is a Brazilian berry known for its therapeutic potential against cancer, obesity, insulin resistance (IR), and others. It is a natural source of bioactive compounds, leading to better glucose metabolism, and attenuating obesity and IR through the reduction of pro-inflammatory status. The present study aimed to observe the prebiotic effect of freeze-dried jabuticaba peel (J) consumption on gut bacteria profile and describe its effects on IR derived from the lipopolysaccharides/Toll-like receptor-4 inflammatory pathway. Jabuticaba peel was chemically characterized, and its bioactive compounds were quantified. Twenty-four C57BL/6 mice were feed with a control diet (n = 6), control diet + J (n = 6), high-fat diet (HF) (n = 6), and HF + J (n = 6) for thirteen weeks. Gut bacteriota (16s RNA sequencing), glucose metabolism (fasting glucose and insulin, OGTT, ITT, HOMA-IR, and ß, QUICKI), and inflammatory status (serum lipopolysaccharide, and protein expression) were assessed. The main bioactive compounds found in J were dietary fiber, and anthocyanins, and its consumption along with a healthy diet reduced the abundance of Firmicutes and Actinobacteriota phyla (p < 0.01), increased the Muribaculaceae and Lachnospiraceae families, and Faecalicatena genus (p < 0.05). The correlation test indicates a negative correlation between the Muribaculaceae and glucose metabolism. Jabuticaba peel is a nutritive source of bioactive compounds with prebiotic effects.

Systemic antioxidant and anti-inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression.

We evaluated the impact of yellow passion fruit (Passiflora edulis sp.) bagasse extract (PFBE) administration in systemic oxidative and inflammatory parameters in vivo, considering prostate cancer progression in transgenic mice (TRAMP). Piceatannol, scirpusin-B, dicaffeoylquinic acid, citric acid, and (+)-catechin were identified in PFBE, and the extract showed high in vitro antioxidant capacity. Some alterations in systemic parameters were verified during prostate cancer progression, as the increase in ALT and MDA levels, and SOD and GPx activities in the plasma. In the liver, higher MDA, TNF-α, and NF-κB levels, and GR and GPx activities were verified. Compared to their respective controls, the short- and long-term PFBE administration reduced MDA levels in the liver and plasma. The long-term treatment increased the catalase activity in the plasma, while the short-term treatment increased the hepatic SOD and catalase activities. Still, a reduction in hepatic TNF-α and NF-κB levels was verified after long-term treatment. PRACTICAL APPLICATIONS: Prostate cancer progression is associated with changes in systemic redox status and inflammation markers. Moreover, the intake of polyphenols with antioxidant properties, besides delaying prostate carcinogenesis, may improve the systemic antioxidant defenses and inflammatory response. In vitro studies pointed to a promising antioxidant and anti-inflammatory potential of yellow passion fruit bagasse. However, in vivo studies are scarce. Our results provided information about in vivo impacts of PFBE oral consumption on antioxidant defense and inflammation, indicating its potential as an adjuvant during the initial steps of prostate cancer.

Prevention of Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Mice by Yellow Passion Fruit Extract and Antiproliferative Effects of Its Bioactive Compound Piceatannol.

Piceatannol (PIC), a polyphenol presents in many vegetables and fruits including yellow passion fruit extract (PFE; Passiflora edulis), has anti-cancer activity, but its molecular targets are still poorly understood. The aims of this study were to investigate the molecular mechanistic actions of PIC in prostate cancer cell lines and to test if the extract from PFE rich in PIC can affect the growth of prostate cancer cells in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The PC-3, 22Rv1, LNCaP, and VCaP prostate cancer cells were exposed to PIC (10-40 µM), and cell viability, lactate measurement, Western blot, and flow cytometric analyses were performed. For an in vivo experiments, eight-week-old TRAMP mice (n = 10 per group each) received an aqueous extract of PFE containing 20 mg of PIC/kg or water (control group) by gavage for 4 or 10 weeks for further analyses. PIC treatment concentration- and time-dependently reduced viability of all cell lines tested. 22Rv1 and LNCaP cells treated with PIC did not exhibit any significant alteration in the intracellular accumulation of lactate. PIC treatment caused G0/G1 phase cell cycle arrest and induction of apoptosis in both LNCaP and 22Rv1 cells. PIC-treated cells exhibited altered protein levels of p53, p21, cyclin D1, and cyclin-dependent kinase 4 (cdk4). The short and long-term PFE treatments also affected p21, cyclin D1 and cdk4 and delayed disease progression in TRAMP, with a decreased incidence of preneoplastic lesions. In conclusion, PIC apparently does not alter glucose metabolism in prostate cancer cells, while cell cycle arrest and p53 modulation are likely important in anti-cancer effects of PIC alone or as a food matrix byproduct in prostate cancer cells, especially those with an androgen-dependent phenotype.

High-fat diet effects on the prostatic adenocarcinoma model and jaboticaba peel extract intake: protective response in metabolic disorders and liver histopathology.

Prostate cancer (PCa), overweight and obesity are frequent worldwide health problems. Clinical studies have shown that increased high-fat diet (HFD) consumption is associated with higher incidence of PCa. Brazilian berries, such as Myrciaria jaboticaba (Vell.) Berg, present high polyphenol concentration in the peel and exhibit positive effects on metabolic disorders and hepatic lesions. Therefore, the aim of the study herein was to investigate the patented jaboticaba peel extract effects (PJE) on different metabolic parameters and liver histopathology in the transgenic adenocarcinoma of the mouse prostate model, receiving a either normolipid diet or HFD for 8 weeks. The results showed that PJE reduced insulin resistance and glucose intolerance, decreased hepatic lipid accumulation, and inflammatory markers such as PPARγ and TNFα, respectively. In conclusion, the PJE treatment promoted protective effects in the metabolism of insulin and glucose and liver imbalance caused by HFD intake in the PCa model, suggesting that it may be a good protector against metabolic disorders present in overweight and associated with PCa.

Avaliação do sistema Petrifilm™ HS na contagem de coliformes em leite pasteurizado / Evaluation of the Petrifilm™ HS system for counting coliforms in pasteurized milk

Os métodos microbiológicos alternativos apresentam vantagens sobre os ensaios convencionais, no entanto é preciso confirmar sua eficácia. O presente trabalho avaliou o sistema Petrifilm™ HS com o sistema Petrifilm™ EC, em comparação com a metodologia convencional na contagem de coliformes a 35 ºC em leite pasteurizado. Altas correlações foram encontradas entre as metodologias utilizadas para efetuar a contagem de coliformes a 35 ºC. O sistema Petrifilm™ HS para contagem de coliformes a 35 ºCem leite pasteurizado mostrou resultados satisfatórios...