RESUMO
Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.
Assuntos
Pesquisa Biomédica , Células Cultivadas , Neoplasias , Feminino , Humanos , Masculino , Publicações , Fatores Sexuais , SexismoRESUMO
AIMS: This study aimed to evaluate the efficacy of paraprobiotics Lactobacillus acidophilus PIN7 supplementation against dextran sodium sulphate (DSS)-induced colitis in mice and to determine their mechanisms of the action. METHODS AND RESULTS: Ten-week-old female BALB/C mice were randomly divided into five groups. Each group was administered with PBS (control and DSS group), live PIN7 (LIVE group), heat-killed PIN7 (HEAT group) or lysozyme-treated PIN7 (LYSOZYME group) for 10 days followed by 2.5% DSS supply in drinking water for 5 days except for the control group. Colitis-associated DAI scores were significantly (p < 0.05) attenuated in HEAT and LYSOZYME group. The HEAT group exhibited significantly (p < 0.05) lower colonic tissue damage score compared to the DSS group. Furthermore, HEAT and LYSOZYME groups showed significantly (p < 0.05) higher colonic expressions of toll-like receptor (TLR) 6 and intestinal junction protein E-cadherin and occludin compared to the DSS group. LYSOZYME group showed significantly (p < 0.05) lower colonic expressions of Th2 cell-associated pro-inflammatory molecules, namely GATA3 and IL-4, and higher expression of anti-inflammatory NLRP6 and IL-18 compared to the DSS group. Also, HEAT group exhibited significantly (p < 0.05) lower colonic p-IκBα expression compared to the DSS group, while COX-2 expression was significantly (p < 0.05) suppressed by both paraprobiotics supplementation. Paraprobiotics significantly altered the composition of the intestinal microbiota. CONCLUSION: Paraprobiotic L. acidophilus PIN7 ameliorated DSS-induced colitis by regulating immune-modulatory TLR6 signalling and gut microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests paraprobiotic L. acidophilus PIN7 are superior candidates to prevent intestinal inflammation associated with dysregulated immune responses.
Assuntos
Colite , Probióticos , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Modelos Animais de Doenças , Feminino , Lactobacillus acidophilus , Camundongos , Camundongos Endogâmicos BALB C , Probióticos/farmacologiaRESUMO
Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Gastrointestinais/genética , Neoplasias Hepáticas/genética , Obesidade/genética , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/patologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Humanos , Inflamação/genética , Inflamação/microbiologia , Inflamação/patologia , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Obesidade/complicações , Obesidade/patologia , Fatores de Risco , Caracteres SexuaisRESUMO
BACKGROUND: More than half of the adult population worldwide is overweight or obese, while excess adiposity has been linked to chronic low-grade inflammation, contributing to the development of chronic diseases. Recent studies have showed that diet-induced alterations to the gut microbiota composition play a pivotal role in the development of obesity. However, the cause-effect relationship between obesity and gut microbiota composition is not yet fully understood. In this study, we investigated the short-term responses of gut microbiota composition to diets with different fat contents and their associations with inflammatory biomarkers. RESULTS: Sixty male C57BL/6 J mice were fed a normal diet (ND; 15% fat) or a high-fat diet (HFD; 45% fat) for 10 or 20 weeks. The relative proportion of the phylum Actinobacteria was elevated by the HFD and was positively associated with body weight and proinflammatory cytokines including TNF-α, IL-1ß, and IL-6. The proportion of the phylum Firmicutes increased with aging and was also positively correlated with proinflammatory cytokines. The proportions of Actinobacteria and Firmicutes were inversely associated with tight junction proteins claudin-1 and E-cadherin, respectively. The proportions of the class Clostridia and the family Ruminococcaceae within the phylum Firmicutes were affected by both diet and age. In addition, the proportions of the phylum Bacteroidetes, the family Bacteroidaceae, and the genus Bacteroides decreased with aging and were inversely correlated with colonic proinflammatory cytokines representing a positive association with tight junction proteins. CONCLUSIONS: Host age and dietary fat intake are important elements that induce proportional changes in gut microbiota, and these changes are also associated with systemic inflammation. This study provides evidence that diet affects the gut microbiota composition within a short period of time.
Assuntos
Colo/imunologia , Gorduras na Dieta/metabolismo , Microbioma Gastrointestinal , Obesidade/metabolismo , Obesidade/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Colo/microbiologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologiaRESUMO
BACKGROUND: Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. METHODS: Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. RESULTS: PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (<3.5 g/dL), and 66.2% had NRI score less than 97.5 indicating moderate to severe malnutrition. Hematological adverse events were present in 94% (≥grade 1) and 16.2% (≥grade 3). Non-hematological adverse events occurred in 95.7% (≥grade1) and 16.7% (≥grade 3) of the patients. PG-SGA and NRI score was not associated with treatment-induced adverse events. Multivariate analyses indicated that female, low body mass index, and hypoalbuminemia were independent risk factors for grade 3/4 hematological adverse events. Age was an independent risk factor for grade 3/4 non-hematological adverse events. Neutropenia was the most frequently occurring adverse event, and associated risk factors were female, total gastrectomy, and hypoalbuminemia. CONCLUSIONS: Hypoalbuminemia, not PG-SGA or NRI may predict chemotherapy-induced adverse events in gastrectomized cancer patients.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Avaliação Nutricional , Estado Nutricional , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Índice de Massa Corporal , Constipação Intestinal/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neutropenia Febril/etiologia , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Hipoalbuminemia/complicações , Modelos Logísticos , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Análise Multivariada , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Neoplasias Gástricas/cirurgia , Vômito/etiologiaRESUMO
Osteoporosis is a degenerative bone disease characterized by low bone mass and is caused by an imbalance between osteoblastic bone formation and osteoclastic bone resorption. It is known that the bioactive compounds present in green tea increase osteogenic activity and decrease the risk of fracture by improving bone mineral density. However, the detailed mechanism underlying these beneficial effects has yet to be elucidated. In this study, we investigated the osteogenic effect of (-)-epicatechin gallate (ECG), a major bioactive compound found in green tea. We found that ECG effectively stimulates osteoblast differentiation, indicated by the increased expression of osteoblastic marker genes. Up-regulation of osteoblast marker genes is mediated by increased expression and interaction of the transcriptional coactivator with PDZ-binding motif (TAZ) and Runt-related transcription factor 2 (RUNX2). ECG facilitates nuclear localization of TAZ through PP1A. PP1A is essential for osteoblast differentiation because inhibition of PP1A activity was shown to suppress ECG-mediated osteogenic differentiation. Taken together, the results showed that ECG stimulates osteoblast differentiation through the activation of TAZ and RUNX2, revealing a novel mechanism for green tea-stimulated osteoblast differentiation.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Catequina/análogos & derivados , Diferenciação Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteoblastos/metabolismo , Fatores de Transcrição/biossíntese , Ativação Transcricional/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/fisiologia , Aciltransferases , Animais , Catequina/farmacologia , Diferenciação Celular/fisiologia , Linhagem Celular , Núcleo Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Humanos , Camundongos , Osteoblastos/citologia , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional/fisiologiaRESUMO
A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPARα/γ/δ activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPARγ/δ activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPARγ. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology.
Assuntos
Álcoois/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Ácidos Indolacéticos/farmacologia , PPAR delta/agonistas , PPAR gama/agonistas , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Desenho de Fármacos , Jejum , Regulação da Expressão Gênica , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/síntese química , Ácidos Indolacéticos/síntese química , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/patologia , PPAR delta/genética , PPAR delta/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Rosiglitazona , Transdução de Sinais , Tiazolidinedionas/farmacologiaRESUMO
BACKGROUND: Carnosic acid (CA), a major bioactive component of rosemary (Rosmarinus officinalis) leaves, is known to possess antioxidant and anti-adipogenic activities. In this study it was hypothesized that CA would ameliorate obesity-induced glucose intolerence and hepatic fat accumulation, and possible mechanisms are suggested. RESULTS: It was observed that a 0.02% (w/w) CA diet effectively decreased body weight, liver weight and blood triglyceride (TG) and total cholesterol levels (P < 0.05) compared with the control diet. CA at 0.02% significantly improved glucose tolerance, and hepatic TG accumulation was reduced in a dose-dependent manner. Hepatic lipogenic-related gene (L-FABP, SCD1 and FAS) expression decreased whereas lipolysis-related gene (CPT1) expression increased in animals fed the 0.02% CA diet (P < 0.05). Long-chain fatty acid content and the ratio of C18:1/C18:0 fatty acids were decreased in adipose tissue of animals fed the 0.02% CA diet (P < 0.05). Serum inflammatory mediators were also decreased significantly in animals fed the 0.02% CA diet compared with those of the obese control group (P < 0.05). CONCLUSION: These results suggest that CA is an effective anti-obesity agent that regulates fatty acid metabolism in C57BL/6J-ob/ob mice.
Assuntos
Abietanos/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Regulação Enzimológica da Expressão Gênica , Intolerância à Glucose/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/dietoterapia , Extratos Vegetais/uso terapêutico , Abietanos/administração & dosagem , Animais , Fármacos Antiobesidade/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Carnitina O-Palmitoiltransferase/química , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Intolerância à Glucose/etiologia , Hiperlipidemias/etiologia , Hiperlipidemias/prevenção & controle , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Tamanho do Órgão , Extratos Vegetais/administração & dosagem , Estearoil-CoA Dessaturase/antagonistas & inibidores , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Redução de PesoRESUMO
In this study we investigated the effects of luteolin supplementation (0.05% w/w) on mammary tumor growth in C3H mice, a strain of mouse mammary tumor virus negative, fed either high-fat (45% fat of energy) or low-fat diet (15% fat of energy). Animals (n = 12/group) were allocated into 4 experimental groups (low-fat diet, low-fat diet + luteolin supplementation, high-fat diet, high-fat diet + luteolin supplementation). Experimental diet were fed for 13 wk and 7,12-dimethylbenz[a]anthracene was administered once a week for 6 wk starting at Week 1 to induce mammary tumors. Study results showed that animals on low-fat diet supplemented with luteolin exhibited longer tumor latency and lower tumor weights and sizes compared to the other groups. Animals fed high-fat diet showed increased serum IGF-1 levels and the elevated mammary tissue expression of Ki-67, IRS-1, pp38, Cdk4, and Cdk6. Luteolin inhibited IRS-1, Cdk4, and Cdk6 expression in high-fat fed animals. The expression of pp38, cyclinD1, and Bcl-xL was suppressed by luteolin supplementation both in the low-fat and high-fat diet groups. These results suggest that excess energy supply increases the risk of mammary tumor formation and luteolin suppresses tumor formation regardless of dietary fat content through its cell cycle regulatory and proapoptotic activity.
Assuntos
Luteolina/farmacologia , Neoplasias Mamárias Experimentais/dietoterapia , Animais , Apoptose/efeitos dos fármacos , Dieta Hiperlipídica , Suplementos Nutricionais , Ingestão de Energia/efeitos dos fármacos , Feminino , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Camundongos Endogâmicos C3H , Transdução de Sinais/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND AND AIM: Epidemiological evidences suggested an inverse association between the use of glucosamine supplements and colorectal cancer (CRC) risk. In this study, the efficacy of glucosamine to attenuate dextran sodium sulfate (DSS)-induced colitis, a precancerous condition for CRC, was evaluated. METHODS: C57BL/6 mice were separated into three groups receiving glucosamine sulfate at concentrations of 0, 0.05, and 0.10% (w/w) of AIN-93G diet, respectively for 4 weeks. Colitis was induced by supplying two cycles (5 days per cycle) of 2% DSS in the animals' drinking water. RESULTS: Glucosamine supplementation at the level of 0.10% of the diet (w/w) reduced colitis-associated symptoms as measured by disease activity index (DAI). Tumor necrosis factor-α (TNF-α), interleukin-1ß, and nuclear factor-kappa B mRNA expression in the colonic mucosa was significantly lower in animals fed 0.10% glucosamine compared with those of the control group. Expression of the tight junction proteins ZO-1 and occludin was significantly higher in the 0.10% glucosamine-supplemented group compared with the other groups. Also, colonic protein expression of lipocalin 2, and serum concentrations of interleukin-8 and amyloid P component (SAP) were significantly reduced in the 0.10% glucosamine-supplemented group compared with the control group. CONCLUSION: These results suggest that glucosamine attenuates the colitis disease activity by suppressing NF-κB activation and related inflammatory responses.
Assuntos
Colite/prevenção & controle , Colo/metabolismo , Suplementos Nutricionais , Glucosamina/administração & dosagem , Mediadores da Inflamação/metabolismo , Proteínas de Fase Aguda/metabolismo , Administração Oral , Animais , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Expressão Gênica , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/sangue , Lipocalina-2 , Lipocalinas/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Ocludina/metabolismo , Proteínas Oncogênicas/metabolismo , Lesões Pré-Cancerosas , RNA Mensageiro/metabolismo , Componente Amiloide P Sérico/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Skeletal muscle inflammation and atrophy are closely associated with metabolic impairment such as insulin resistance. Quercetin, a natural polyphenol flavonoid, is known to elicit anti-inflammatory and antioxidant activities. In this study, we investigated its effect on obesity-induced skeletal muscle inflammation and atrophy in mice. Male C57BL/6 mice were fed a regular diet, a high-fat diet (HFD), and an HFD supplemented with quercetin for nine weeks. Quercetin reduced levels of inflammatory cytokines and macrophage accumulation in the skeletal muscle of the HFD-fed obese mice. It also reduced transcript and protein levels of the specific atrophic factors, Atrogin-1 and MuRF1, in the skeletal muscle of the HFD-fed obese mice, and protected against the reduction of muscle mass and muscle fiber size. In vitro, quercetin markedly diminished transcript levels of inflammatory receptors and activation of their signaling molecules (ERK, p38 MAPK, and NF-κB) in cocultured myotubes/macrophages, and this was accompanied by reduced expression of the atrophic factors. Together, these findings suggest that quercetin reduces obesity-induced skeletal muscle atrophy by inhibiting inflammatory receptors and their signaling pathway. Quercetin may be useful for preventing obesity-induced muscle inflammation and sarcopenia.
Assuntos
Antioxidantes/química , Atrofia/patologia , Inflamação/patologia , Músculo Esquelético/patologia , Obesidade/complicações , Quercetina/química , Animais , Sequência de Bases , Linhagem Celular , Citocinas/metabolismo , Inflamação/metabolismo , Resistência à Insulina , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Sarcopenia/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor ß activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Isotiocianatos/farmacologia , Macrófagos/efeitos dos fármacos , Pele/efeitos dos fármacos , Verduras/química , Animais , Anti-Inflamatórios/química , Ciclo-Oxigenase 2/imunologia , Citocinas/imunologia , Feminino , Proteínas I-kappa B/imunologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Isotiocianatos/química , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Camundongos , Inibidor de NF-kappaB alfa , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Pele/imunologia , Acetato de Tetradecanoilforbol/análogos & derivadosRESUMO
Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 µmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration.
Assuntos
Abietanos/farmacologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Melanoma/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Fatores de Transcrição da Família Snail , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Vimentina/genética , Vimentina/metabolismoRESUMO
Excess oxidative stress generated in the body causes various types of cellular damage, including DNA damage. Certain trace minerals act as antioxidants by functioning as cofactors for antioxidant enzymes. This study was conducted to evaluate the serum and hair concentrations of major antioxidant trace minerals (zinc, manganese, selenium, and chromium) and to determine the association between the oxidative stress marker urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum or hair antioxidant trace mineral concentrations, according to the general characteristics of healthy adults. Study participants were selected after screening, and 108 participants aged 19-69 years were finally included. Serum and hair trace mineral concentrations were analyzed using inductively coupled plasma mass spectrometry, and urine 8-OHdG levels were quantified using an ELISA kit. Results showed that urinary 8-OHdG levels were significantly higher in exercisers than in those who did not exercise. Correlation analysis revealed that urinary 8-OHdG was negatively correlated with hair zinc in participants over 60 years of age and with poor health status, and positively correlated with hair chromium in participants with irregular dietary habits. In conclusion, these results suggest that urinary 8-OHdG is particularly correlated with hair zinc and chromium levels. Additional large-scale epidemiological studies are needed to generally confirm these findings.
Assuntos
Selênio , Oligoelementos , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Antioxidantes/metabolismo , Oligoelementos/análise , Estudos Transversais , Estresse Oxidativo , Selênio/metabolismo , Zinco/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Cromo/metabolismo , Cabelo/química , Desoxiguanosina/metabolismoRESUMO
This study investigated the sex-specific correlation between obesity and colorectal cancer emphasizing a more pronounced association in males. Estrogen, chromosomal genes, and gut bacteria were assessed in C57BL6/J male, female and ovariectomized (OVX) female mice, subjected to either a low-fat diet (LFD) or high-fat diet (HFD) for 14 weeks. Induction of colon tumor involved azoxymethane (10 mg/kg) administration, followed by three cycles of dextran sulfate sodium. Male mice on HFD exhibited higher final body weight and increased colon tumors compared to females. Colonic mucin 2 expression was significantly higher in females. HFD-modulated differentially expressed genes numbered 290 for males, 64 for females, and 137 for OVX females. Only one up-regulated gene (Gfra3) overlapped between females and OVX females, while two down-regulated genes (Thrsp and Gbp11) overlapped between males and OVX females. Genes up-regulated by HFD in males were linked to cytokine-cytokine interaction, HIF-1 signaling pathway, central carbon metabolism in cancer. Sex-specific changes in gut microbial composition in response to HFD were observed. These findings suggest a male-specific vulnerability to HFD-induced colon tumor formation, implicating key genes and colonic bacteria in colon tumorigenesis.
Assuntos
Neoplasias do Colo , Microbiota , Feminino , Masculino , Animais , Camundongos , Caracteres Sexuais , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Dieta Hiperlipídica/efeitos adversos , Citocinas , Expressão Gênica , Camundongos Endogâmicos C57BLRESUMO
Over the past decade, an unexpected cooling trend has been observed in East Asia and North America during winter. Climate model simulations suggest that this pattern of stalled warming, besides accelerated warming, will repeat throughout the course of global warming, influenced by the natural decade-long variations in the climate system. However, understanding the exact factors affecting the pace of warming remains a challenge. Here we show that a pause in warming over continental areas-namely, local warming hiatus-can be accompanied by excessive heat accumulation north of the ocean fronts. This oceanic condition, often manifesting in the form of marine heatwaves, constrains the subseasonal growth of atmospheric planetary waves, significantly increasing the likelihood of cold extremes in downstream continents. Our results underscore the importance of closely monitoring changing ocean fronts in response to human-induced warming, which can potentially reshape the inherent decade-long fluctuations within regional climates over the long term.
RESUMO
Ulcerative colitis (UC) is a chronic gastrointestinal disease whose incidence is increasing rapidly worldwide. Anti-inflammatory medications, including 5-aminosalicylic acid (5-ASA), corticosteroids, and immunosuppressants, are used for its treatment; however, new alternatives would be required due to the serious side effects of some of these medications. N-Acetylglucosamine (NAG) is an amino sugar composed of mucin that is secreted by intestinal epithelial cells. It is also used to promote the growth of intestinal bacteria. The current study aimed to determine the efficacy of NAG against dextran sulfate sodium (DSS)-induced chronic colitis and elucidate its mechanism of action. Mice were randomly divided into control, DSS, 0.1% sulfasalazine, 0.1% NAG, 0.3% NAG, and 0.3% NAG-dimer (NAG-D) groups, and results showed that colitis-induced body weight loss, disease activity, colonic tissue damage, colon length shortening, and the loss of mucin-secreting area were significantly improved in the NAG-D group. The intestinal permeability indicator, serum CD 14 level, and expression of the tight junction protein, occludin, were both improved in the 0.3% NAG group. Inflammatory biomarkers, including GATA3, IFN-γ, p-IκBα, COX2, TGF-ß1, and Smad7, were significantly lower in the 0.3% NAG and NAG-D groups than in the DSS group. The intestinal microbial composition was most significantly altered in the 0.3% NAG group, showing decreased ratios of pathogenic bacteria, such as Betaproteobacteria, especially Burkholderiales. The results overall suggested that NAG or NAG-D supplementation can alleviate inflammation by strengthening the intestinal barrier function and maintaining gut microbiota homeostasis in a DSS-induced colitis mouse model.
Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Acetilglucosamina , Colite/induzido quimicamente , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológicoRESUMO
We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right flank. Solid tumor growth and the number and volume of tumor nodules in the lung were increased markedly in the HFD group with only a slight increase in body weight (5.9%). HFD feeding increased tumor tissue levels of Ki67, cyclin A, cyclin D1, CDK2, Bcl-xL, and Bcl-2; reduced p53 levels and TUNEL-positive apoptotic cells; increased the levels of CD45, CD68, CD31, VEGF, P-VEGF receptor-2, iNOS, and COX-2 as well as hemoglobin content; and increased the levels of HIF-1α, P-STAT3-Y705, P-STAT3-S727, P-IκB-α, P-p65, p65, P-c-Jun, P-Akt, P-ERK1/2, P-p38, and P-SAPK/JNK. HFD feeding increased the serum levels of EGF, insulin, IGF-I, IFN-γ, leptin, RANTES, MCP-1, IL-1ra, and SDF-1α and media conditioned by epididymal fat tissue explants from HFD-fed mice caused an increase in microvessel outgrowth from the mouse aorta and tube formation of human umbilical vein endothelial cells. These results indicate that the chronic consumption of an HFD increases colon cancer cell proliferation, tumor angiogenesis, and lung metastasis in mice in the absence of discernible weight gain. HFD feeding increases the levels of growth factors which activate transcription factors, thereby inducing the expression of many genes involved in the stimulation of inflammation, angiogenesis, and cellular proliferation.
Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Dieta Hiperlipídica/efeitos adversos , Neoplasias Pulmonares/secundário , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Colo/imunologia , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/imunologia , Citocinas/sangue , Citocinas/imunologia , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/imunologia , Obesidade/metabolismoRESUMO
This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata) root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v), providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME) exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR) 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR-) mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Codonopsis/química , Fígado Gorduroso Alcoólico/prevenção & controle , Reguladores do Metabolismo de Lipídeos/administração & dosagem , Extratos Vegetais/administração & dosagem , Adenosina/genética , Adenosina/metabolismo , Animais , Colesterol/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: This study was performed to evaluate the effects of high vegetable-fruit (high-VF) and low vegetable-fruit (low-VF) diet on surrogate biomarkers of adiposity-related metabolic disturbances. METHODS: Overweight women (n=22, 19-29 years) participated in the study between July and August, 2007 in Seoul, Korea. The intervention consisted of either high-VF diet (12 servings of VF/day) or low-VF diet (2 servings of VF/day). Plasma concentration of carotenoids and biomarkers of inflammation and oxidative stress were determined before and after each intervention period. RESULTS: Study results indicated that body fat content is positively correlated with plasma interleukin (IL)-6, C-reactive protein (CRP), and leptin concentrations at baseline. Oxidative DNA damage and lipopolysaccharide (LPS)-activated production of IL-1ß and IL-6 in peripheral blood mononuclear cells (PBMCs) were decreased with high-VF diet while low-VF diet increased those markers. Changes in the concentration of plasma total carotenoid and ß-carotene were inversely correlated with change in plasma IL-1ß concentration. Differences in IL-ß production in LPS-activated PBMCs were inversely correlated with changes in plasma concentration of lutein-zeaxanthin. Also, changes in plasma total carotenoid and lycopene concentration were inversely correlated with the changes in IL-6 production in LPS-activated PBMCs. CONCLUSION: Daily intake of vegetables and fruits can modify adiposity-related metabolic disturbances.