RESUMO
Photobioreactors (PBRs) are used to grow the light-requiring microalgae in diverse commercial processes. Often, they are operated as continuous culture over months period. However, with time, biofouling layer develops on the inner surfaces of their walls. The fouling layer formation deteriorates the PBR performance as foulants reduce light penetration in it. Light is essential for photosynthetic cultures, and a deterioration in lighting adversely impacts algae growth and biomass productivity. Fouling requires a frequent shutdown to clean the PBR and add to the environmental impact of the operation by generating many wastewaters contaminated with the cleaning chemicals. Antibiofouling coatings could be used to modify the surfaces of existing and future PBRs. Therefore, transparent and non-toxic fouling-release coatings, produced using hydrogel technology, could transform the existing PBRs into efficient and enduring microalgae culture systems, requiring only the application of the coating to the inner walls, without additional investments in new PBRs.
Assuntos
Incrustação Biológica , Microalgas , Fotobiorreatores , Microalgas/crescimento & desenvolvimento , Incrustação Biológica/prevenção & controle , Biomassa , LuzRESUMO
Advances made in pancreatic cancer therapy have been far from sufficient and have allowed only a slight improvement in global survival of patients with pancreatic ductal adenocarcinoma (PDA). Recent progresses in chemotherapy have offered some hope for an otherwise gloomy outlook, however, only a limited number of patients are eligible because of important cytotoxicity. In this context, enhancing our knowledge on PDA initiation and evolution is crucial to highlight certain weaknesses on which to specifically target therapy. We found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted PDA development. In two relevant and specific engineered pancreatic cancer mouse models, we observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). Through proteomic analysis of conditioned media from TAp73 wild-type (WT) and deficient pancreatic tumor cells, we identified a secreted protein, biglycan (BGN), which is necessary and sufficient to mediate this pro-EMT effect. Interestingly, BGN is modulated by and modulates the transforming growth factor-ß (TGF-ß) pathway, a key regulator of the EMT process. We further examined this link and revealed that TAp73 impacts the TGF-ß pathway by direct regulation of BGN expression and Sma and Mad-related proteins (SMADs) expression/activity. Absence of TAp73 leads to activation of TGF-ß signaling through a SMAD-independent pathway, favoring oncogenic TGF-ß effects and EMT. Altogether, our data highlight the implication of TAp73 in the aggressiveness of pancreatic carcinogenesis through modulation of the TGF-ß signaling. By suggesting TAp73 as a predictive marker for response to TGF-ß inhibitors, our study could improve the classification of PDA patients with a view to offering combined therapy involving TGF-ß inhibitors.
Assuntos
Carcinoma Ductal Pancreático/patologia , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Biglicano/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Interferência de RNA , Transdução de Sinais/fisiologia , Taxa de Sobrevida , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/farmacologia , Células Tumorais CultivadasRESUMO
Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/ß-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Caderinas/metabolismo , Comunicação Celular/efeitos dos fármacos , Compartimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Meios de Cultura/farmacologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neoplasias Pancreáticas/genética , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Células de Schwann/patologia , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Transcriptoma/genética , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , beta Catenina/metabolismo , Neoplasias PancreáticasRESUMO
This paper focuses on the activity spectrum of three dimethylalkyl tertiary amines as potential active molecules and the corresponding ammonium salt-based antifouling (AF) paints. Bioassays (using marine bacteria, microalgae and barnacles) and field tests were combined to assess the AF activity of coatings. Bioassay results demonstrated that the ammonium salt-based paints did not inhibit the growth of microorganisms (except the dimethyldodecylammonium-based coatings) and that the tertiary amines were potent towards bacteria, diatoms, and barnacle larvae at non-toxic concentrations (therapeutic ratio, LC50/EC50, <1). The results from field tests indicated that the ammonium salt-based coatings inhibited the settlement of macrofouling and the dimethylhexadecylammonium-based coatings provided protection against slime in comparison with PVC blank panels. Thus, results from laboratory assays did not fully concur with the AF activity of the paints in the field trial.