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In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H 2 O 2 ) to induce oxidative stress activation and BZF treatment was administered at the same moment as H 2 O 2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H 2 O 2 -induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H 2 O 2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H 2 O 2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis. Graphical Abstract

The objective of this study was to evaluate the antitumor activity of lipophilic bismuth nanoparticles (BisBAL NPs) on breast cancer cells. The effect of varying concentrations of BisBAL NPs was evaluated on human MCF-7 breast cancer cells and on MCF-10A fibrocystic mammary epitheliocytes as noncancer control cells. Cell viability was evaluated with the MTT assay, plasma membrane integrity was analyzed with the calcein AM assay, genotoxicity with the comet assay, and apoptosis with the Annexin V/7-AAD assay. BisBAL NPs were spherical in shape (average diameter, 28 nm) and agglomerated into dense electronic clusters. BisBAL NP induced a dose-dependent growth inhibition. Most importantly, growth inhibition was higher for MCF-7 cells than for MCF-10A cells. At 1 µM BisBAL NP, MCF-7 growth inhibition was 51%, while it was 11% for MCF-10A; at 25 µM BisBAL NP, the growth inhibition was 81% for MCF-7 and 24% for MCF-10A. With respect to mechanisms of action, a 24-hour exposure of 10 and 100 µM BisBAL NP caused loss of cell membrane integrity and fragmentation of tumor cell DNA. BisBAL NPs at 10 µM were genotoxic to and caused apoptosis of breast cancer cells. BisBAL NP-induced growth inhibition is dose dependent, and breast cancer cells are more vulnerable than noncancer breast cells. The mechanism of action of BisBAL NPs may include loss of plasma membrane integrity and a genotoxic effect on the genomic DNA of breast cancer cells.

The incidence of hepatocellular carcinoma (HCC) keeps rising year by year, and became the second leading cause of cancer-related death. Some studies have found that liraglutide, a GLP-1 analog, may decrease the tumor cells proliferation. Due to this, the aim of this work is to investigate the antiproliferative potential of exenatide, another GLP-1 analog. Cell proliferation was assessed by direct count with Trypan blue dye exclusion. Flow cytometry was used to determinate autophagy and nuclear staining. Morphometric analysis was used to verify senescence and apoptosis. The mechanism that induced cell growth inhibition was analyzed by Western Blot. Treatment with exenatide significantly decreases cell proliferation and increases autophagy, both in relation to control and liraglutide. In addition, mTOR inhibition was greater in cells treated with exenatide. In relation to chronic treatment, exenatide does not allow cellular regrowth by preventing some resistance mechanism that the cells can acquire. These results suggest that exenatide has a potent anti-proliferative activity via mTOR modulation and, among the GLP-1 analogs tested, could be in the future an alternative for HCC treatment.

Objective: Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism. Material and methods: The human breast tumor cells MCF-7 and no-tumor breast cells MCF-10A were exposed to CPC under various condition (concentration and duration). Cell viability was measured with MTT assay, the LIVE/DEAD assay, and fluorescence microscopy. Membrane permeability after CPC exposure was evaluated by Calcein AM assay, mitochondrial morphology with a MitoView staining, and genotoxicity with the comet assay and fluorescence microscopy. Results: CPC was cytotoxic to both MCF-7 and MCF-10A as of a 24-h exposure to 0.1 µM. Cytotoxicity was dose-dependent and reached 91% for MCF-7 and 78% for MCF-10A after a 24-h exposure to 100 µM CPC, which outperformed the positive control doxorubicin in effectiveness and selectivity. The LD50 of CPC on was 6 µM for MCF-7 and 8 µM for MCF-10A, yielding a selectivity index of 1.41. A time response analysis revealed 64% dead cells after only 5 min of exposure to 100 µM CPC. With respect to the action mechanisms, the comet assay did not reveal genome fragmentation. On the other hand, membrane damage was dose-dependent and may also affect mitochondrial morphology. Conclusion: Cetylpyridinium chloride inhibits MCF-7 cell growing in a non-selective way as of 5 min of exposure. The action mechanism of CPC on tumor cells involves cell membrane damage without change neither mitochondrial morphology nor genotoxicity.

SummaryHepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.

Electricity data is one of the key factors in life cycle assessment (LCA). There are two different approaches to model electricity and to apply average or marginal data in LCA studies. Marginal data is used in consequential whereas average data is considered in attributional studies. The aim of this study is to provide the long-term marginal technology for electricity power generation in Colombia until 2030. This technology is one capable of responding to small changes in demand on the market and is an important issue when assessing the environmental impacts of providing electricity. Colombia is a developing country with a national power grid, which historically has been dominated by Hydropower rather than fossil fuels. This particularity makes Colombian national power grid vulnerable to climatic variations; therefore, the country needs to introduce renewable resources into the power grid. This study uses consequential life cycle assessment and data from Colombian national plans for capacity changes in the power grid. The results show that whereas marginal electricity technology would most probably be Hydropower, Wind and Solar power are projected to reach more than 1% of the national power grid by 2030.

Octyl gallate (OG) is an antioxidant commonly used in food, although there is no definition of its acceptable daily intake. There are reports and showing that food additives and drugs can alter lipid metabolism. Lipid droplet accumulation in hepatic cells is one of the main findings in the unregulated lipid metabolism and is strongly related to the development of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of OG on lipid metabolism in the hepatocellular carcinoma cell line (HepG2). The results have shown, for the first time, that treatment with OG increased the overall amount of lipids, the triglyceride concentration, the lipid droplet area, and SREBP-1c and PPAR-γ gene expression. Taken together, the findings indicate that OG induces lipid droplet accumulation in HepG2 cells through the regulation of SREBP-1c and PPAR-γ gene expression without involving mTOR/S6K1 and may contribute to NAFLD when used as a food additive.

A reconfiguração dos modelos de Bem-Estar traduz-se na tendência para a territorialização das políticas públicas, no geral e das sociais no particular, reabrindo-se caminho para a dimensão comunitária do Serviço Social, especialmente relevante no campo empírico da ação social local.Compreender as dinâmicas de territorialização das políticas sociais e qual o papel do Serviço Social neste processo, constrói-se, em torno da constatação de que a realidade é socialmente construída, por isso subjetiva, num processo contínuo de busca de compreensãosobre os fenómenos sociais e na procura de construção de uma teoria de e na ação.Organiza-se a investigação em torno da pergunta de partida: Como influencia a prática do Serviço Social as dinâmicas de territorialização das políticas sociais? e de métodos mistos.A narrativa enfoca a pertinência de se impulsionar as matrizes teórico-metodológicas do Serviço Social comunitário e de reposicionar o mesmo perante outras áreas de saber no que concerne à intervenção comunitária, atendendo à sua focalização no trabalho de caso, à pouca expressão da sua participação nas dinâmicas de planeamento, liderança, co-gestão de redes, o que exige uma visão crítica reflexiva da sua ação, que vise a capacitação e empoderamento dos assistentes sociais para a intervenção comunitária, assente na ligação entre a academia e a prática.A dimensão comunitária do Serviço Social não só é atual como tem intencionalidade e indissociabilidade com as políticas sociais no âmbito da territorialização das políticas sociais.

Objective: To determine and characterize the antitumor activity of a hydrogel loaded with octenidine hydrochloride (OCTH) and its action mechanism on human tumor cells. Material and methods: The antibiofilm property of OCTH against a clinical methicillin-resistant Staphylococcus aureus isolate (MRSA-CI) was evaluated by disk diffusion assays and a human bone-biofilm model in combination with the BacLight™ staining. The antitumor activity of soluble OCTH and OCTH-loaded biodegradable hydrogels was assessed in human tumor cell lines (MCF-7, CAL-27, FaDu, and A549) under different experimental conditions. Cell viability was measured with the MTT assay, and membrane permeability after OCTH-loaded hydrogel exposure was evaluated with the Calcein AM assay. Genotoxicity was evaluated with comet assay and fluorescence microscopy. Results: A stable, transparent, and biodegradable OCTH hydrogel with a pH of 7.2 was successfully developed. Biofilms exposed to 50 μm OCTH for 24 h exhibited only dead bacteria (red fluorescence), comparable to the effect of 100 μm vancomycin. Soluble OCTH demonstrated dose-dependent inhibition of tumor cell growth in all tested cell lines, with significant effects observed from 1 μm. The LD50 values for soluble OCTH across the tumor cell lines ranged from 2.32 to 5.1 µm. Notably, hydrogel loaded with 50 μm OCTH significantly reduced cell growth by 44% after a 15-min exposure and by 97% after 120 min. The Calcein AM assay revealed that OCTH’s antitumor mechanism involves the disruption of tumor cell plasma membrane permeability. Conclusion: This study is the first that describes the antitumor activity of octenidine hydrochloride on different human tumor cell lines. A biodegradable hydrogel loaded with octenidine hydrochloride constitutes an innovative, low-cost alternative for the topical treatment of cancer.

Objective: To evaluate the antitumor and antimicrobial properties of an alginate-based membrane (ABM) loaded with bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) on clinically isolated bacteria and a pancreatic cancer cell line. Material and methods: The BisBAL NP-CPC ABM was characterized using optical and scanning electron microscopy (SEM). The antimicrobial potential was measured using the disk-diffusion assay, and antibiofilm activity was determined through the live/dead assay and fluorescence microscopy. The antitumor activity was analyzed on the pancreatic cell line (Panc 03.27) using the MTT assay and live/dead assay with fluorescence microscopy. Results: After a 24-h exposure (37°C, aerobic conditions), 5 µM BisBAL NP reduced the growth of K. pneumoniae by 77.9%, while 2.5 µM BisBAL NP inhibited the growth of Salmonella, E. faecalis and E. faecium by 82.9%, 82.6%, and 78%, respectively (p < 0.0001). The BisBAL NPs-CPC ABM (at a ratio of 10:1; 500 and 50 µM, respectively) inhibited the growth of all isolated bacteria, producing inhibition halos of 9.5, 11.2, 7, and 10.3 mm for K. pneumoniae, Salmonella, E. faecalis, and E. faecium, respectively, in contrast to the 6.5, 9.5, 8.5, and 9.8 mm obtained with 100 µM ceftriaxone (p < 0.0001). The BisBAL NPs-CPC ABM also reduced bacterial biofilms, with 81.4%, 74.5%, 97.1%, and 79.5% inhibition for K. pneumoniae, E. faecium, E. faecalis, and Salmonella, respectively. Furthermore, the BisBAL NPs-CPC ABM decreased Panc 03.27 cell growth by 76%, compared to 18% for drug-free ABM. GEM-ABM reduced tumoral growth by 73%. The live/dead assay confirmed that BisBAL NPs-CPC-ABM and GEM-ABM were cytotoxic for the turmoral Panc 03.27 cells. Conclusion: An alginate-based membrane loaded with BisBAL NP and CPC exhibits dual antimicrobial and antitumoral efficacy. Therefore, it could be applied in cancer treatment and to diminish the occurrence of surgical site infections.