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1.
Gut Microbes ; 16(1): 2356642, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769708

RESUMO

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.


Assuntos
Aderência Bacteriana , Biofilmes , Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli , Regulação Bacteriana da Expressão Gênica , Macrófagos , Macrófagos/microbiologia , Animais , Camundongos , Escherichia coli/genética , Escherichia coli/patogenicidade , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Biofilmes/crescimento & desenvolvimento , Infecções por Escherichia coli/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Virulência , Colite/microbiologia , Doença de Crohn/microbiologia , Modelos Animais de Doenças , Transdução de Sinais , Ácidos/metabolismo
2.
Appl Environ Microbiol ; 90(4): e0150023, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38456674

RESUMO

Plasmalogen is a specific glycerophospholipid present in both animal and bacterial organisms. It plays a crucial function in eukaryotic cellular processes and is closely related to several human diseases, including neurological disorders and cancers. Nonetheless, the precise biological role of plasmalogen in bacteria is not well understood. In this study, we identified SMU_438c as the enzyme responsible for plasmalogen production in Streptococcus mutans under anaerobic conditions. The heterologous expression of SMU_438c in a plasmalogen-negative strain, Streptococcus sanguinis, resulted in the production of plasmalogen, indicating that this enzyme is sufficient for plasmalogen production. Additionally, the plasmalogen-deficient S. mutans exhibited significantly lower acid tolerance and diminished its colonization in Drosophila flies compared to the wild-type strain and complemented strain. In summary, our data suggest that plasmalogen plays a vital role in bacterial stress tolerance and in vivo colonization. IMPORTANCE: This study sheds light on the biological role of plasmalogen, a specific glycerophospholipid, in bacteria, particularly in Streptococcus mutans. Plasmalogens are known for their significant roles in eukaryotic cells and have been linked to human diseases like neurological disorders and cancers. The enzyme SMU_438c, identified as essential for plasmalogen production under anaerobic conditions, was crucial for acid tolerance and in vivo colonization in Drosophila by S. mutans, underscoring its importance in bacterial stress response and colonization. These findings bridge the knowledge gap in bacterial physiology, highlighting plasmalogen's role in microbial survival and offering potential insights into microbial pathogenesis and host-microbe interactions.


Assuntos
Neoplasias , Doenças do Sistema Nervoso , Humanos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Plasmalogênios/metabolismo , Streptococcus mutans/metabolismo , Ácidos/metabolismo , Drosophila , Biofilmes
3.
Aquat Toxicol ; 268: 106865, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377931

RESUMO

Freshwater acidification is a global environmental challenge, yet the effects of acidic water on fish resistance to toxic Ag+ remain an unexplored area. To address this knowledge gap, zebrafish embryos were exposed to different concentrations (0 (control), 0.1, and 0.25 mg/L) of AgNO3 under pH 5 or 7 for 7 days. Notably, AgNO3 at 0.25 mg/L resulted in 100 % mortality in both pH conditions, while AgNO3 at 0.1 mg/L resulted in higher mortality at pH 5 (85 %) compared to pH 7 (20 %), indicating that acidic water enhanced Ag+ toxicity. Several parameters, including body length, inner ear (otic vesicle and otolith) and yolk sac areas, lateral line hair cell number and morphology, the number of ionocytes (H+-ATP-rich cells and Na+/K+-ATP-rich cells), and ion contents (Ag+, Na+, and Ca2+) were assessed at 96 h (day 4) to investigate individual and combined effects of Ag+ and acid on embryos. Acid alone did not significantly alter most parameters, but it decreased the yolk sac area and increased the ionocyte number. Conversely, Ag+ alone caused reductions in most parameters, including body length, the inner ear area, hair cell number, and ionocyte number. Combining acid and Ag+ resulted in greater suppression of the otolith area, hair cell number, and Na+/Ca2+ contents. In conclusion, acidification of freshwater poses a potential risk to fish embryo viability by increasing their susceptibility to silver toxicity, specifically affecting sensory function and ion regulation.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Prata/toxicidade , Água/farmacologia , Embrião não Mamífero , Poluentes Químicos da Água/toxicidade , Ácidos/metabolismo , Trifosfato de Adenosina/metabolismo
4.
Food Chem Toxicol ; 185: 114446, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244666

RESUMO

The aberrant increase or dysregulation of cytosolic Zn2+ concentration ([Zn2+]cyt) has been associated with cellular dysfunction and cytotoxicity. In this study, we postulated that Zn2+ mediates the cytotoxicity of thiol-reactive electrophiles. This notion was grounded on earlier research, which revealed that thiol-reactive electrophiles may disrupt Zn2+-binding motifs, consequently causing Zn2+ to be released from Zn2+-binding proteins, and leading to a surge in [Zn2+]cyt. The thiol-reactive electrophiles N-ethylmaleimide (NEM) and diamide were observed to induce an increase in [Zn2+]cyt, possibly through the impairment of Zn2+-binding motifs, and subsequent stimulation of reactive oxygen species (ROS) formation, resulting in cytotoxicity in primary cultured rat vascular smooth muscle cells. These processes were negated by the thiol donor N-acetyl-L-cysteine and the Zn2+ chelator TPEN. Similar outcomes were detected with co-treatment involving Zn2+ and Zn2+ ionophores such as pyrithione or disulfiram. Moreover, TPEN was found to inhibit cytotoxicity triggered by short-term exposure to various thiol-reactive electrophiles including hydrogen peroxide, acrylamide, acrylonitrile, diethyl maleate, iodoacetic acid, and iodoacetamide. In conclusion, our findings suggest that cytosolic Zn2+ acts as a universal mediator in the cytotoxic effects produced by thiol-reactive electrophiles.


Assuntos
Etilenodiaminas , Compostos de Sulfidrila , Zinco , Ratos , Animais , Compostos de Sulfidrila/metabolismo , Zinco/metabolismo , Músculo Liso Vascular/metabolismo , Citosol , Ácidos/metabolismo
5.
World J Microbiol Biotechnol ; 40(2): 53, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38146044

RESUMO

Fermentation is considered an effective tool for improving the functional characteristics of food. In this study, Lacticaseibacillus casei YQ336 was used to ferment yellow whey, and physical and chemical analysis was performed to identify the changes in the nutritional components and antioxidant activity of the fermented yellow whey. Non-targeted metabolomics was used to study the transformation of small molecular substances in the fermented yellow whey. After 48 h of pure culture fermentation with L. casei YQ336, the pH of yellow whey decreased significantly (p < 0.05). Meanwhile, the content of total acids, organic acids, sugars, total phenols, and total flavonoids and the antioxidant activity showed a significant increase (p < 0.05). A total of 628 differential metabolites were identified between fermented and unfermented yellow whey samples, of which 293 were upregulated and 335 were downregulated. After fermentation, due to the growth and metabolic activity of L. casei YQ336, meaningful metabolites such as homovanillic acid, lactic acid, oxalic acid, L-glutamic acid, and phenylalanine, as well as phenyllactic acid, gallic acid, and genistein were produced. This increased the organic acid content and antioxidant activity of yellow whey. The findings provide a theoretical and practical basis for further research on the bio-functional activity of yellow whey and the recycling and utilization of food by-products.


Assuntos
Lacticaseibacillus casei , Soro do Leite , Soro do Leite/metabolismo , Antioxidantes/metabolismo , Fermentação , Proteínas do Soro do Leite/metabolismo , Ácidos/metabolismo , Ácido Láctico/metabolismo
6.
Plant Physiol Biochem ; 203: 108064, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37783071

RESUMO

Aluminum (Al) is the most prevalent element in the earth crust and is toxic to plants in acidic soils. However, plants can address Al toxicity through external exclusion (which prevents Al from entering roots) and internal detoxification (which counterbalances the toxic-Al absorbed by roots). Nowadays, certain categories of exogenously added regulatory factors (EARF), such as nutritional elements, organic acids, amino acids, phytohormones, or biochar, etc. play a critical role in reducing the bioavailability/toxicity of Al in plants. Numerous studies suggest that regulating factors against Al toxicity mediate the expression of Al-responsive genes and transcription factors, thereby regulating the secretion of organic acids, alkalizing rhizosphere pH, modulating cell wall (CW) modifications, improving antioxidant defense systems, and promoting the compartmentalization of non-toxic Al within intracellular. This review primarily discusses recent and older published papers to demonstrate the basic concepts of Al phytotoxicity. Furthermore, we provide a comprehensive explanation of the crucial roles of EARF-induced responses against Al toxicity in plants. This information may serve as a foundation for improving plant resistance to Al and enhancing the growth of susceptible species in acidic soils. And this review holds significant theoretical significance for EARF to improve the quality of acidic soils cultivated land, increase crop yield and quality, and ensure food security.


Assuntos
Alumínio , Plantas , Alumínio/toxicidade , Alumínio/metabolismo , Plantas/metabolismo , Antioxidantes/metabolismo , Raízes de Plantas/metabolismo , Ácidos/metabolismo , Solo/química
7.
Nutrients ; 15(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37513516

RESUMO

Dietary acid load (DAL) is recognized as a risk factor for several chronic disorders, including obesity, diabetes, and osteoporosis. Recent evidence suggests that an elevated DAL, as measured by the validated potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores, could also increase the risk for several cancers. This narrative review summarizes the potential role of DAL in Uruguayan cancer patients and outlines the potentially involved pathophysiological pathways that mediate the role of DAL in both cancer development and growth. Although Uruguay is a developing country, its average diet is a heavily meat-based Western one, translating into a supraphysiological acid burden from diet. In recent years, we have published epidemiologic evidence based on ten case-control studies involving 3736 cancer cases and 9534 hospital-based controls. Odds ratios and 95% confidence intervals were estimated for each interest variable to analyze the association between the exposure levels of DAL scores and cancer, calculated by unconditional logistic regression. In a majority of the cases, the highest DAL scores tended to double the cancer risk as compared to the lowest category. We also found high risks for methionine intake, an acidifying amino acid found in higher concentrations in animal-based foods, which may increase cancer risks at least by a joint action based on the pH and the proliferation enhancing properties of the amino acid itself.


Assuntos
Dieta , Neoplasias , Animais , Uruguai/epidemiologia , Dieta/efeitos adversos , Fatores de Risco , Obesidade/etiologia , Ácidos/metabolismo , Aminoácidos , Neoplasias/etiologia , Neoplasias/complicações
8.
Cells ; 12(9)2023 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-37174623

RESUMO

Different light wavelengths display diverse effects on fruit quality formation and anthocyanin biosynthesis. Blueberry is a kind of fruit rich in anthocyanin with important economic and nutritional values. This study explored the effects of different light wavelengths (white (W), red (R), blue (B) and yellow (Y)) on fruit quality and gene expression of anthocyanin biosynthesis in blueberry. We found that the B and W treatments attained the maximum values of fruit width, fruit height and fruit weight in blueberry fruits. The R treatment attained the maximum activities of superoxide dismutase (SOD) and peroxidase (POD), and the Y treatment displayed the maximum contents of ascorbic acid (AsA), glutathione (GSH) and total phenol in fruits, thus improving blueberry-fruit antioxidant capacity. Interestingly, there were differences in the solidity-acid ratio of fruit under different light-wavelength treatments. Moreover, blue light could significantly improve the expression levels of anthocyanin biosynthesis genes and anthocyanin content in fruits. Correlation and principal component analysis showed that total acid content and antioxidant enzymes were significantly negatively correlated with anthocyanin content in blueberry fruits. These results provide new insights for the application of light wavelength to improve blueberry fruit quality and anthocyanin content.


Assuntos
Mirtilos Azuis (Planta) , Vaccinium , Antioxidantes/metabolismo , Mirtilos Azuis (Planta)/genética , Mirtilos Azuis (Planta)/metabolismo , Antocianinas/metabolismo , Vaccinium/genética , Vaccinium/metabolismo , Frutas/metabolismo , Ácidos/metabolismo , Glutationa/metabolismo , Expressão Gênica
9.
Autophagy ; 19(3): 886-903, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35982578

RESUMO

Dysfunction in the macrophage lysosomal system including reduced acidity and diminished degradative capacity is a hallmark of atherosclerosis, leading to blunted clearance of excess cellular debris and lipids in plaques and contributing to lesion progression. Devising strategies to rescue this macrophage lysosomal dysfunction is a novel therapeutic measure. Nanoparticles have emerged as an effective platform to both target specific tissues and serve as drug delivery vehicles. In most cases, administered nanoparticles are taken up non-selectively by the mononuclear phagocyte system including monocytes/macrophages leading to the undesirable degradation of cargo in lysosomes. We took advantage of this default route to target macrophage lysosomes to rectify their acidity in disease states such as atherosclerosis. Herein, we develop and test two commonly used acidic nanoparticles, poly-lactide-co-glycolic acid (PLGA) and polylactic acid (PLA), both in vitro and in vivo. Our results in cultured macrophages indicate that the PLGA-based nanoparticles are the most effective at trafficking to and enhancing acidification of lysosomes. PLGA nanoparticles also provide functional benefits including enhanced lysosomal degradation, promotion of macroautophagy/autophagy and protein aggregate removal, and reduced apoptosis and inflammasome activation. We demonstrate the utility of this system in vivo, showing nanoparticle accumulation in, and lysosomal acidification of, macrophages in atherosclerotic plaques. Long-term administration of PLGA nanoparticles results in significant reductions in surrogates of plaque complexity with reduced apoptosis, necrotic core formation, and cytotoxic protein aggregates and increased fibrous cap formation. Taken together, our data support the use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in the treatment of atherosclerosis.Abbreviations: BCA: brachiocephalic arteries; FACS: fluorescence activated cell sorting; FITC: fluorescein-5-isothiocyanatel; IL1B: interleukin 1 beta; LAMP: lysosomal associated membrane protein; LIPA/LAL: lipase A, lysosomal acid type; LSDs: lysosomal storage disorders; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFI: mean fluorescence intensity; MPS: mononuclear phagocyte system; PEGHDE: polyethylene glycol hexadecyl ether; PLA: polylactic acid; PLGA: poly-lactide-co-glycolic acid; SQSTM1/p62: sequestosome 1.


Assuntos
Aterosclerose , Nanopartículas , Placa Aterosclerótica , Humanos , Autofagia , Aterosclerose/patologia , Macrófagos/metabolismo , Placa Aterosclerótica/patologia , Lisossomos/metabolismo , Ácidos/metabolismo , Poliésteres/metabolismo
10.
Thorac Cancer ; 13(19): 2759-2766, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36054595

RESUMO

BACKGROUND: A high dietary acid load (DAL) can produce metabolic acidosis, which is linked to cancer development through mechanisms of inflammation and cell transformation. There is limited epidemiological evidence linking DAL and cancer risk; however, none of the published studies focused on DAL and esophageal cancer (EC) risk in particular. Therefore, we sought to explore this association in the present study. METHODS: A case-control study was performed in 1295 male patients (185 squamous cell EC cases and 1110 age-frequency and urban/rural residence matched controls) through a multitopic inquiry, including a food frequency questionnaire. Food-derived nutrients were calculated from available databases. The DAL was calculated based on two validated measures: Potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Odds ratios (OR) and their 95% confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusting for confounders. RESULTS: We found direct, significant associations between dietary acid load and EC risk: (OR = 2.28, 95% CI: 1.44-3.61, ptrend <0.0001) and (OR = 2.17, 95% CI: 1.38-3.41, ptrend <0.0001) for highest PRAL and NEAP tertiles, respectively. Our data raise the possibility that a high DAL may contribute to EC development. Both acid load scores were directly associated with animal-based foods (mainly meat) and inversely associated with the intake of plant-based foods. CONCLUSION: To the best of our knowledge, this is the first epidemiological case-control study analyzing associations of DAL and squamous cell EC risk. Further research is warranted to confirm our findings.


Assuntos
Dieta , Neoplasias Esofágicas , Ácidos/efeitos adversos , Ácidos/metabolismo , Animais , Estudos de Casos e Controles , Dieta/efeitos adversos , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Humanos , Fatores de Risco
11.
Biotechnol Bioeng ; 119(9): 2471-2481, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35665482

RESUMO

Filamentous fungi occupy a uniquely favorable position in the bioproduction of organic acids. Intracellular stress is the main stimulator in filamentous fungi to produce and accumulate organic acids with high flux. However, stress can affect the physiological activities of filamentous fungi, thereby deteriorating their fermentation performance. Herein, we report that peptide supplementation during Rhizopus oryzae fermentation significantly improved fumaric acid production. Specifically, fumaric acid productivity was elevated by approximately 100%, fermentation duration was shortened from 72 to 36 h, while maintaining the final titer. Furthermore, transcriptome profile analysis and biochemical assays indicated that the overall capabilities of the stress defense systems (enzymatic and nonenzymatic) were significantly improved in R. oryzae. Consequently, glycolytic metabolism was distinctly enhanced, which eventually resulted in improved fumaric acid production and reduced fermentation duration. We expect our findings and efforts to provide essential insights into the optimization of the fermentation performance of filamentous fungi in industrial biotechnology and fermentation engineering.


Assuntos
Fumaratos , Rhizopus , Ácidos/metabolismo , Suplementos Nutricionais , Fermentação , Fumaratos/metabolismo , Fungos/metabolismo , Peptídeos/metabolismo
12.
Int J Mol Sci ; 23(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35163782

RESUMO

Dental caries is caused by the formation of cariogenic biofilm, leading to localized areas of enamel demineralization. Streptococcus mutans, a cariogenic pathogen, has long been considered as a microbial etiology of dental caries. We hypothesized that an antagonistic approach using a prebiotic collagen peptide in combination with probiotic Lactobacillus rhamnosus would modulate the virulence of this cariogenic biofilm. In vitro S. mutans biofilms were formed on saliva-coated hydroxyapatite discs, and the inhibitory effect of a combination of L. rhamnosus and collagen peptide on S. mutans biofilms were evaluated using microbiological, biochemical, confocal imaging, and transcriptomic analyses. The combination of L. rhamnosus with collagen peptide altered acid production by S. mutans, significantly increasing culture pH at an early stage of biofilm formation. Moreover, the 3D architecture of the S. mutans biofilm was greatly compromised when it was in the presence of L. rhamnosus with collagen peptide, resulting in a significant reduction in exopolysaccharide with unstructured and mixed bacterial organization. The presence of L. rhamnosus with collagen peptide modulated the virulence potential of S. mutans via down-regulation of eno, ldh, and atpD corresponding to acid production and proton transportation, whereas aguD associated with alkali production was up-regulated. Gly-Pro-Hyp, a common tripeptide unit of collagen, consistently modulated the cariogenic potential of S. mutans by inhibiting acid production, similar to the bioactivity of a collagen peptide. It also enhanced the relative abundance of commensal streptococci (S. oralis) in a mixed-species biofilm by inhibiting S. mutans colonization and dome-like microcolony formation. This work demonstrates that food-derived synbiotics may offer a useful means of disrupting cariogenic communities and maintaining microbial homeostasis.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Colágeno/química , Lacticaseibacillus rhamnosus/fisiologia , Peptídeos/farmacologia , Streptococcus mutans/fisiologia , Ácidos/metabolismo , Terapia Combinada , Meios de Cultura/química , Cárie Dentária/microbiologia , Cárie Dentária/prevenção & controle , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Microscopia Confocal , Polissacarídeos Bacterianos/metabolismo , Probióticos , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/metabolismo
13.
Biochem Biophys Res Commun ; 592: 38-43, 2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35026603

RESUMO

Ovarian cancer is the deadliest gynecological cancer which rarely causes symptoms, and goes undetected until reaching the advanced stage of drug-resistant metastases. The cationic porphyrin meso-tetra(4-N-methylpyridyl)porphine (TMPyP) is a well-known photosensitizer (PS) used in photodyamic therapy (PDT) for curing cancer due to its strong affinity for DNA and high yield of reactive oxygen species (ROS) upon light activation. The practicality to irradiate tumor cells alone in the physiological system being slim (due to the close proximity of healthy cells and tumors), we looked for a variation in the PDT using a mixture of TMPyP with 1,5-dihydroxynapthalene (DHN) and Fe(III) ions at a mole ratio of 1:20:17 (drug combo) respectively in aqueous solution. The drug combo needs no photoactivation in H2O2 rich environment (mimicking the microenvironment of cancer/tumor), where it generates È®H and juglone, the latter being a known potent anticancer agent. In vitro studies of the drug combo in drug resistant and sensitive ovarian cancer cell lines showed drastic growth inhibition and cell death compared to normal epithelial cells. The drug combo provides an effective and non-invasive alternative to conventional PDT, exploiting the cytosolic carcinogenic H2O2 to produce an efficient anticancer treatment. The unique action of cancer-specific cytotoxicity arises from the redox chemistry involving activation of Fe(III) as the oxidizing agent to generate juglone, which utilizes the cytosolic ROS in cancer cells against itself.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ácidos/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos , Naftóis/farmacologia , Naftoquinonas/farmacologia , Oxirredução , Porfirinas/farmacologia , Espectrometria de Fluorescência
14.
Environ Technol ; 43(16): 2516-2529, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33512309

RESUMO

Heavy metal immobilization using biochar (BC) is different from the usual soil incubation due to the low molecular weight organic acids (LMWOAs) in the rhizosphere and is an issue worth evaluating. Therefore, the impacts of rice husk BC (5%), tartaric acid, and oxalic acid, coupled with combinations of BC and tartaric acid/oxalic acid on the transformation of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms, including their bioavailability in a metal-contaminated soil, were investigated in an incubation experiment. The application of BC, low concentration of tartaric acid (2 mmol kg-1 soil) (TA2), and the combined BC plus a low level of tartaric acid (BC-TA2) markedly reduced the acid-soluble and available (CaCl2-extractable) Cd, Pb, and Zn compared to control (CK) in which BC-TA2 was found to be the most effective treatment. The trends were reversed in the case of the high concentrations of tartaric acid (>5-20 mmol kg-1 soil), all levels of oxalic acid (2-20 mmol kg-1 soil), and the combined BC plus high levels of tartaric acid/oxalic acid treatments. The BC-TA2 transformed the highest amounts of acid-soluble and reducible Cd, Pb, and Zn to the oxidizable and residual fractions with incubation time. The results suggested that the low concentration of tartaric acid enhanced Cd, Pb, and Zn immobilization, while the higher level of tartaric acid and all concentrations of oxalic acid increased their mobilization. In conclusion, BC-TA2 could immobilize the most heavy metals and serve as an amendment for metals' immobilization/redistribution in contaminated soils.


Assuntos
Metais Pesados , Oryza , Poluentes do Solo , Ácidos/metabolismo , Cádmio/química , Carvão Vegetal/química , Chumbo/metabolismo , Metais Pesados/análise , Peso Molecular , Compostos Orgânicos/metabolismo , Oryza/química , Oxalatos/metabolismo , Solo/química , Poluentes do Solo/química , Zinco/química
15.
Cells ; 10(12)2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34943819

RESUMO

The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.


Assuntos
Ácidos/metabolismo , Progressão da Doença , Exossomos/metabolismo , Melanoma/patologia , Microambiente Tumoral , Hipóxia Celular/genética , Redes Reguladoras de Genes , Humanos , Melanoma/genética , Melanoma/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
16.
Cell Death Dis ; 12(11): 1040, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725334

RESUMO

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) regulates cell and whole-body metabolism and supports tumorigenesis. The cellular impacts of perturbing CAMKK2 expression are, however, not yet fully characterised. By knocking down CAMKK2 levels, we have identified a number of significant subcellular changes indicative of perturbations in vesicle trafficking within the endomembrane compartment. To determine how they might contribute to effects on cell proliferation, we have used proteomics to identify Gemin4 as a direct interactor, capable of binding CAMKK2 and COPI subunits. Prompted by this, we confirmed that CAMKK2 knockdown leads to concomitant and significant reductions in δ-COP protein. Using imaging, we show that CAMKK2 knockdown leads to Golgi expansion, the induction of ER stress, abortive autophagy and impaired lysosomal acidification. All are phenotypes of COPI depletion. Based on our findings, we hypothesise that CAMKK2 sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking.


Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Complexo de Golgi/metabolismo , Neoplasias/enzimologia , Neoplasias/patologia , Vesículas Transportadoras/metabolismo , Ácidos/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Autofagia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/química , Linhagem Celular Tumoral , Proliferação de Células , Complexo I de Proteína do Envoltório/metabolismo , Sequência Conservada , Complexo de Golgi/ultraestrutura , Homeostase , Humanos , Lisossomos/metabolismo , Antígenos de Histocompatibilidade Menor/química , Antígenos de Histocompatibilidade Menor/metabolismo , Peptídeos/metabolismo , Ligação Proteica , Domínios Proteicos , RNA Interferente Pequeno/metabolismo , Ribonucleoproteínas Nucleares Pequenas/química , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Resposta a Proteínas não Dobradas
17.
Cells ; 10(10)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34685701

RESUMO

A hallmark of malignant solid tumor is extracellular acidification coupled with metabolic switch to aerobic glycolysis. Using the human MCF10A progression model of breast cancer, we show that glycolytic switch and extracellular acidosis in aggressive cancer cells correlate with increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), known to induce intracellular signal transduction through the interaction with its cell surface receptor CD63, independent of its metalloproteinase inhibitory function. We found that, in aggressive breast carcinoma, the TIMP-1-CD63 signaling axis induced a metabolic switch by upregulating the rate of aerobic glycolysis, lowering mitochondrial respiration, preventing intracellular acidification, and inducing extracellular acidosis. Carbonic anhydrase IX (CAIX), a regulator of cellular pH through the hydration of metabolically released pericellular CO2, was identified as a downstream mediator of the TIMP-1-CD63 signaling axis responsible for extracellular acidosis. Consistently with our previous study, the TIMP-1-CD63 signaling promoted survival of breast cancer cells. Interestingly, breast carcinoma cell survival was drastically reduced upon shRNA-mediated knockdown of CAIX expression, demonstrating the significance of CAIX-regulated pH in the TIMP-1-CD63-mediated cancer cell survival. Taken together, the present study demonstrates the functional significance of TIMP-1-CD63-CAXI signaling axis in the regulation of tumor metabolism, extracellular acidosis, and survival of breast carcinoma. We propose that this axis may serve as a novel therapeutic target.


Assuntos
Neoplasias da Mama/metabolismo , Tetraspanina 30/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Ácidos/metabolismo , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Progressão da Doença , Espaço Extracelular/metabolismo , Feminino , Humanos , Modelos Biológicos , Invasividade Neoplásica
18.
Nutrients ; 13(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371931

RESUMO

The purpose of this study was to examine the independent and joint associations of acid-producing diets and depressive symptoms with physical health among breast cancer survivors. We studied a cohort of 2944 early stage breast cancer survivors who provided dietary, physical health, demographic, and lifestyle information at baseline, year 1, and year 4. We assessed the intakes of acid-producing diets via two commonly used dietary acid load scores: potential renal acid load (PRAL) and net endogenous acid production (NEAP). Physical health was measured using the Rand 36-Item Short Form Health Survey (SF-36), consisting of physical functioning, role limitation due to physical function, bodily pain, general health, and overall physical health subscales. Increased dietary acid load and depression were each independently and significantly associated with reduced physical health subscales and overall physical health. Further, dietary acid load and depression were jointly associated with worse physical health. For instance, depressed women with dietary acid load higher than median reported 2.75 times the risk (odds ratio = 2.75; 95% confidence interval: 2.18-3.47) of reduced physical function and 3.10 times the risk of poor physical health (odds ratio = 3.10; 95% confidence interval: 2.53-3.80) compared to non-depressed women with dietary acid load lower than median. Our results highlight the need of controlling acid-producing diets and the access of mental care for breast cancer survivors.


Assuntos
Ácidos/efeitos adversos , Afeto , Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Depressão/complicações , Dieta/efeitos adversos , Saúde Mental , Ácidos/metabolismo , Adulto , Depressão/diagnóstico , Depressão/psicologia , Feminino , Nível de Saúde , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201855

RESUMO

The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet-gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (ß = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (ß = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.


Assuntos
Ácidos/metabolismo , Dieta , Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Característica Quantitativa Herdável , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interleucina-6/genética , Rim/metabolismo , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade
20.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204744

RESUMO

The cambuci is a native Brazilian fruit from the Atlantic Forest biome. A soft and astringent pulp, a green color, and a sweet aroma are its main characteristics. Classical food quality attributes (fresh fruit mass, fruit height, diameters, total soluble solid, titratable acidity, and ratio) and the metabolic profile from ten accessions from three different locations were analyzed herein by analytical methods (refractometry and neutralization titration) and nuclear magnetic resonance spectroscopy. Concerning sugar content, sucrose was the predominant compound, with glucose and fructose alternating in second, depending on the accession. Citric acid was the most relevant acid, followed by shikimic and quinic acids in quite variable amounts. These three main acids vary in amounts for each accession. Ascorbic acid content emerges as an important quality attribute and makes this fruit nutritionally attractive, due to values comparable to those contained in citric fruits. The main amino acids identified in cambuci were glutamic acid individually or in comprising the tripeptide glutathione (glutamic acid, cysteine, glycine). The quality diversity of the evaluated accessions suggests the potentiality of cambuci use in future breeding programs.


Assuntos
Frutas/química , Frutas/metabolismo , Myrtaceae/metabolismo , Ácidos/metabolismo , Antioxidantes/análise , Ácido Ascórbico/análise , Brasil , Carboidratos/análise , Qualidade dos Alimentos , Frutose/metabolismo , Glucose/metabolismo , Metaboloma , Metabolômica/métodos , Floresta Úmida
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