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1.
Front Endocrinol (Lausanne) ; 15: 1265799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414818

RESUMO

Introduction: A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice. Methods: C57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells. Results and discussion: Fish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas ß-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function.


Assuntos
Gorduras na Dieta , Ilhotas Pancreáticas , Leptina , Masculino , Camundongos , Animais , Glucagon , Sacarose/efeitos adversos , Óleos de Peixe/farmacologia , Peptídeo C , Camundongos Endogâmicos C57BL , Ilhotas Pancreáticas/metabolismo , Insulina , Glucose , Peptídeo 1 Semelhante ao Glucagon/metabolismo
2.
Toxins (Basel) ; 16(2)2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38393178

RESUMO

The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time.


Assuntos
Toxinas Botulínicas Tipo A , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Excipientes , Polissorbatos , Anticorpos Neutralizantes , Sacarose
3.
J Ethnopharmacol ; 325: 117891, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38331122

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Parishin C (Par), a prominent bioactive compound in Gastrodia elata Blume with little toxicity and shown neuroprotective effects. However, its impact on depression remains largely unexplored. AIM OF THE STUDY: This study aims to investigate the antidepressant effects of Par using a chronic social defeat stress (CSDS) mouse model and elucidate its molecular mechanisms. MATERIALS AND METHODS: The CSDS-induced depression mouse model was used to evaluate the therapeutic efficacy of Par. The social interaction test (SIT) and sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were conducted to assess the effects of Par on depressive-like behaviours. The levels of corticosterone, neurotransmitters (5-HT, DA and NE) and inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay (ELISA). Activation of a microglia was assessed by immunofluorescence labeling Iba-1. The protein expressions of NLRP3, ASC, caspase-1, and IL-6 verified by Western blot. RESULT: Oral administration of Par (4 and 8 mg/kg) and fluoxetine (10 mg/kg, administration significantly ameliorate depression-like behaviors induced by CSDS, as shown by the increase social interaction in SIT, increase sucrose preference in SPT and the decrease immobility in TST and FST. Par administration decreased serum corticosterone level and increased the 5-HT, DA and NE concentration in the hippocampus and prefrontal cortex. Furthermore, Par treatment suppressed microglial activation (Iba1) as well as reduced levels of IL-1ß, TNF-α, and IL-6) with decreased protein expressions of NLRP3, ASC, caspase-1, and IL-6. CONCLUSIONS: our study provides the first evidence that Par exerts antidepressant-like effects in mice with CSDS-induced depression. This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.


Assuntos
Glucosídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fator de Necrose Tumoral alfa , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Derrota Social , Corticosterona , Serotonina/metabolismo , Comportamento Animal , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo , Sacarose/metabolismo , Caspases/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
4.
BMC Plant Biol ; 24(1): 121, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373932

RESUMO

BACKGROUND: The primary challenge in the cut flower industry, specifically in the postharvest phase, is the short vase life of flowers. This issue, along with early leaf yellowing and perianth abscission, significantly diminishes the economic value of flowers due to their accelerated senescence. To tackle this, we conducted a factorial experiment on Alstroemeria cv. Rebecca, utilizing a completely randomized design with three replications. In this experiment the effects of varying concentrations of Salicylic acid (SA) (0, 1.5, and 3 mM) and sucrose (SU) (0% and 3%) were investigated on the postharvest quality of leaves and florets, with systematic evaluations every three days throughout their vase life. RESULTS: This experiment revealed that the specific treatment combination of 1.5 mM SA + 3% SU (T5) markedly improved various parameters, such as vase life, total chlorophyll content, membrane stability index, relative fresh weight, and water uptake of cut flowers. In our analysis, we observed that this preservative solution not only extended the vase life and enhanced water uptake but also effectively preserved total chlorophyll, mitigated the loss of fresh weight, and reduced membrane deterioration in petals. Additionally, our results showed an increase in the activities of catalase (CAT) and peroxidase (POD) enzymes, as well as total protein content, alongside a decrease in malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels. Moreover, this study noted a decrease in microbial populations in solutions containing different concentrations of salicylic acid. CONCLUSIONS: Our research demonstrated that alstroemeria flowers maintained in a solution with 1.5 mM SA + 3% SU exhibited a significantly prolonged vase life of up to 21 days, in contrast to the 15 days observed in control flowers kept in water. These results are highly beneficial for manufacturers in the cut flower industry, as they provide a viable method to substantially extend the vase life of cut flowers. Such an enhancement in flower longevity can lead to increased market value and customer satisfaction. Furthermore, the reduction in flower senescence and decay rates can contribute to decreased waste and greater efficiency in cut flower distribution and sales, offering a substantial advantage to manufacturers in this competitive market. The extended vase life and reduced senescence observed in alstroemeria flowers treated with 1.5 mM SA and 3% SU are attributed to SA's role in enhancing endogenous defense responses and sucrose's function as an energy source, collectively improving water uptake, and delaying the natural decay process.


Assuntos
Alstroemeria , Alstroemeria/metabolismo , Sacarose/farmacologia , Ácido Salicílico/farmacologia , Peróxido de Hidrogênio/farmacologia , Flores/metabolismo , Água/metabolismo , Clorofila
5.
Sci Rep ; 14(1): 3173, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326332

RESUMO

This research represents a novel study to assess how coculture affects levan yield, structure, bioactivities, and molecular weight. Among the 16 honey isolates, four bacterial strains recorded the highest levan yield. The Plackett-Burman design showed that the coculture (M) of isolates G2 and K2 had the maximum levan yield (52 g/L) and the effective factors were sucrose, incubation time, and sugarcane bagasse. The CCD showed that the most proper concentrations for maximum levan yield (81 g/L): were 130 g/L of sucrose and 6 g/f of sugarcane bagasse. Levan's backbone was characterized, and the molecular weight was determined. G2 and K2 isolates were identified based on 16 sRNA as Bacillus megaterium strain YM1C10 and Rhizobium sp. G6-1. M levan had promising antioxidant activity (99.66%), slowed the migration activity to a great extent, and recorded 70.70% inhibition against the hepatoblastoma cell line (HepG2) at 1000 µg/mL. Gene expression analysis in liver cancer cell lines (HePG2) revealed that M levan decreased the expression of CCL20), 2GRB2, and CCR6) genes and was superior to Doxo. While increasing the expression of the IL4R and IL-10 genes. The DNA damage values were significantly increased (P < 0.01) in treated liver cancer cell lines with levan M and Doxo. The results referred to the importance of each of the hydroxyl and carboxyl groups and the molecular weight in levans bioactivities.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Saccharum , Celulose , Carcinoma Hepatocelular/genética , Técnicas de Cocultura , Neoplasias Hepáticas/genética , Saccharum/metabolismo , Frutanos/metabolismo , Bactérias/metabolismo , Sacarose/metabolismo , Linhagem Celular
6.
Sci Rep ; 14(1): 3684, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355653

RESUMO

Vegetable drinks offer a convenient way to increase the daily intake of vegetables containing vitamins, antioxidants, and fiber. In this study, we discovered that mungbean milk serves as a carbohydrate source during fermentation using lactic acid bacteria (LAB) and enhances the nutritional value of vegetable yoghurt. Mungbean milk reduces pH while titratable acidity increases faster than soybean milk during fermentation. M0S, Soybean milk 100% with added sucrose exhibited the highest titratable acidity after 16 h of fermentation. The acetic acid content of all samples did not show significant changes during fermentation, but the lactic acid content increased. Proximate analysis showed no significant change during fermentation, regardless of the fermentation time and mixing ratio of mungbean to soybean milk. The sucrose content of samples except M0S decreased after 16 h of fermentation. Mungbean milk exhibited high antioxidant activity both before and after fermentation, while M0S showed the lowest antioxidant activity. The results of this study demonstrated the potential application of mungbean milk to improve fermented vegetable drinks using LAB functionally. Fermented mungbean milk yoghurt can be a valuable addition to a healthy and balanced diet for those who consume plant-based diets.


Assuntos
Antioxidantes , Lactobacillales , Animais , Antioxidantes/análise , Iogurte/microbiologia , Vitaminas/análise , Carboidratos/análise , Verduras , Leite/química , Sacarose/análise , Fermentação
7.
Bioresour Technol ; 395: 130395, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301939

RESUMO

Currently, levan is attracting attention due to its promising applications in the food and biomedical fields. Levansucrase synthesizes levan by polymerizing the fructosyl unit in sucrose. However, a large amount of the byproduct glucose is produced during this process. In this paper, an engineered oleaginous yeast (Yarrowia lipolytica) strain was constructed using a surface display plasmid containing the LevS gene of Gluconobacter sp. MP2116. The levansucrase activity of the engineered yeast strain reached 327.8 U/g of cell dry weight. The maximal levan concentration (58.9 g/l) was achieved within 156 h in the 5-liter fermentation. Over 81.2 % of the sucrose was enzymolyzed by the levansucrase, and the byproduct glucose was converted to 21.8 g/l biomass with an intracellular oil content of 25.5 % (w/w). The obtained oil was comprised of 91.3 % long-chain fatty acids (C16-C18). This study provides new insight for levan production and comprehensive utilization of the byproduct in levan biosynthesis.


Assuntos
Hexosiltransferases , Yarrowia , Yarrowia/genética , Yarrowia/metabolismo , Glucose , Frutanos/metabolismo , Sacarose/metabolismo
8.
ACS Synth Biol ; 13(2): 658-668, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38319655

RESUMO

The use of Paenibacillus polymyxa as an industrial producer is limited by the lack of suitable synthetic biology tools. In this study, we identified a native sucrose operon in P. polymyxa. Its structural and functional relationship analysis revealed the presence of multiple regulatory elements, including four ScrR-binding sites and a catabolite-responsive element (CRE). In P. polymyxa, we established a cascade T7 expression system involving an integrated T7 RNA polymerase (T7P) regulated by the sucrose operon and a T7 promoter. It enables controllable gene expression by sucrose and regulatory elements, and a 5-fold increase in expression efficiency compared with the original sucrose operon was achieved. Further deletion of SacB in P. polymyxa resulted in a 38.95% increase in the level of thermophilic lipase (TrLip) production using the cascade T7 induction system. The results highlight the effectiveness of sucrose regulation as a novel synthetic biology tool, which facilitates exploring gene circuits and enables their dynamic regulation.


Assuntos
Paenibacillus polymyxa , Paenibacillus polymyxa/genética , Paenibacillus polymyxa/metabolismo , Sacarose/metabolismo , Regiões Promotoras Genéticas/genética , Óperon/genética
9.
Physiol Behav ; 276: 114483, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331375

RESUMO

The increasing prevalence of diabetes is of particular concern in women of childbearing age because of the short and long-term consequences of maternal diabetes for the health of the offspring, such as a greater risk of developing metabolic impairments and cognitive deficits. In addition, maternal diet during pregnancy and lactation might contribute to preventing or ameliorating adverse offspring outcomes. Recently, we described that access to snacks exacerbates glucose intolerance in mildly hyperglycemic pregnant dams. Therefore, we hypothesized that these offspring would show greater impairment in metabolic and behavioral outcomes across the lifespan. Neonatal STZ treatment was employed to induce maternal mild hyperglycemia in females. After mating, normo- and hyperglycemic dams were given access either to standard chow or standard show plus snacks. Male and female offspring were evaluated on postnatal days (PND) 30, 90, and 360. Offspring behavior was assessed in the marble burying task, the open-field test, the elevated-plus maze, and sucrose preference. Glucose tolerance and morphometric analyses were also carried out. Maternal hyperglycemia increased body weight and fat deposition only on PND 30, while retroperitoneal fat deposition was reduced in the offspring of snack-fed dams. However, maternal snack intake reduced offspring body weight and length on PND 90. Fasting glucose was increased in females born to hyperglycemic, snack-fed dams on PND 90. Glucose clearance was altered by both maternal conditions in male offspring on PND 30, however, this sex difference was reversed on PND 90, with maternal hyperglycemia impairing glucose clearance only in females. In addition, maternal hyperglycemia reduced anxiety-like behavior in female offspring on PND 30, especially in the offspring of snack-fed dams, while maternal snack intake reduced sucrose preference in both males and females in adulthood. These results suggest that the effects of maternal hyperglycemia during pregnancy and lactation on offspring outcomes were not exacerbated by snack intake. Although additive effects of the two maternal conditions were hypothesized, the absence of such effects could be related to the mild maternal hyperglycemia induced by STZ treatment even when combined with snack intake. While maternal hyperglycemia alone impaired some offspring outcomes, its association with snack intake did not aggravate those impairments but rather resulted in outcomes more similar to those of offspring born to normoglycemic dams. Finally, females were found to be more susceptible to both the effects of maternal hyperglycemia and snack intake on metabolism and behavior.


Assuntos
Diabetes Mellitus , Intolerância à Glucose , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Recém-Nascido , Feminino , Masculino , Humanos , Lanches , Longevidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Peso Corporal , Glucose , Sacarose , Dieta Hiperlipídica/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna
10.
An Acad Bras Cienc ; 96(1): e20200004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359286

RESUMO

This study aimed to evaluate the impact of Meloidogyne javanica, Meloidogyne incognita, and Meloidogyne arenaria on different aspects of the development of sugarcane plants under greenhouse conditions. For this purpose, seedlings of the RB867515 genotype were individually inoculated with 5,000 eggs + second-stage juveniles of their respective nematodes/plant, and non-inoculated plants were used as control. After 330 days of inoculation, the plants were removed from the pots, and the following characteristics were evaluated: fresh mass of the aerial part and root system; leaf area; leaf chlorophyll index; culm diameter; fresh mass of culms; broth volume; contents of neutral and acid detergent fiber, cellulose, hemicellulose, lignin, apparent sucrose in broth, and reducing sugars in broth; total soluble solids concentration. Subsequently, the final population of nematodes in the root system of inoculated plants was determined to calculate the reproduction factor of nematodes. The results showed that all tested Meloidogyne species negatively affected plant development and the composition of some analyzed fractions, in comparison to the non-inoculated control. However, the presence of the root-knot nematode in sugarcane plants increased the contents of neutral and acid detergent fiber, cellulose, hemicellulose, lignin, and reducing sugars, regardless of the Meloidogyne species.


Assuntos
Saccharum , Tylenchoidea , Animais , Lignina , Detergentes , Celulose , Sacarose
11.
Cancer Med ; 13(2): e6949, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38334474

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia. METHODS: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like 1), in effects of diet timing was studied by overexpression in FLT3-ITD-bearing AML cells. RESULTS: Reduced tumor burden in FLT3-ITD AML-bearing mice was observed with interventions utilizing low-sucrose and/or low-fat diets, or time-restricted feeding (TRF) compared to mice fed normal chow ad libitum. In a tasting study, macronutrient matched low-sucrose and low-fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low-sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3-ITD AML cells. CONCLUSIONS: Mouse models for FLT3-ITD AML show that diet composition and timing slows progression of FLT3-ITD AML growth in vivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Criança , Camundongos , Animais , Fatores de Transcrição ARNTL/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Antineoplásicos/uso terapêutico , Modelos Animais de Doenças , Dieta , Sacarose/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Mutação
12.
BMC Genomics ; 25(1): 166, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347506

RESUMO

BACKGROUND: The carbon metabolism pathway is of paramount importance for the growth and development of plants, exerting a pivotal regulatory role in stress responses. The exacerbation of drought impacts on the plant carbon cycle due to global warming necessitates comprehensive investigation into the response mechanisms of Masson Pine (Pinus massoniana Lamb.), an exemplary pioneer drought-tolerant tree, thereby establishing a foundation for predicting future forest ecosystem responses to climate change. RESULTS: The seedlings of Masson Pine were utilized as experimental materials in this study, and the transcriptome, metabolome, and photosynthesis were assessed under varying temperatures and drought intensities. The findings demonstrated that the impact of high temperature and drought on the photosynthetic rate and transpiration rate of Masson Pine seedlings was more pronounced compared to individual stressors. The analysis of transcriptome data revealed that the carbon metabolic pathways of Masson Pine seedlings were significantly influenced by high temperature and drought co-stress, with a particular impact on genes involved in starch and sucrose metabolism. The metabolome analysis revealed that only trehalose and Galactose 1-phosphate were specifically associated with the starch and sucrose metabolic pathways. Furthermore, the trehalose metabolic heat map was constructed by integrating metabolome and transcriptome data, revealing a significant increase in trehalose levels across all three comparison groups. Additionally, the PmTPS1, PmTPS5, and PmTPPD genes were identified as key regulatory genes governing trehalose accumulation. CONCLUSIONS: The combined effects of high temperature and drought on photosynthetic rate, transpiration rate, transcriptome, and metabolome were more pronounced than those induced by either high temperature or drought alone. Starch and sucrose metabolism emerged as the pivotal carbon metabolic pathways in response to high temperature and drought stress in Masson pine. Trehalose along with PmTPS1, PmTPS5, and PmTPPD genes played crucial roles as metabolites and key regulators within the starch and sucrose metabolism.


Assuntos
Pinus , Pinus/genética , Pinus/metabolismo , Temperatura , Ecossistema , Secas , Carbono/metabolismo , Trealose/metabolismo , Plântula , Sacarose/metabolismo , Amido/metabolismo , Estresse Fisiológico/genética
13.
J Transl Med ; 22(1): 145, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347623

RESUMO

BACKGROUND: Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women's reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear. METHODS: We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS). RESULTS: The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures. CONCLUSIONS: Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Camundongos , Sacarose/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Reprodução , Dieta , Perfilação da Expressão Gênica , Dieta Hiperlipídica/efeitos adversos
14.
Sci Rep ; 14(1): 3077, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321177

RESUMO

Overconsumption of added sugars has been pointed out as a major culprit in the increasing rates of obesity worldwide, contributing to the rising popularity of non-caloric sweeteners. In order to satisfy the growing demand, industrial efforts have been made to purify the sweet-tasting molecules found in the natural sweetener stevia, which are characterized by a sweet taste free of unpleasant aftertaste. Although the use of artificial sweeteners has raised many concerns regarding metabolic health, the impact of purified stevia components on the latter remains poorly studied. The objective of this project was to evaluate the impact of two purified sweet-tasting components of stevia, rebaudioside A and D (RebA and RebD), on the development of obesity, insulin resistance, hepatic health, bile acid profile, and gut microbiota in a mouse model of diet-induced obesity. Male C57BL/6 J mice were fed an obesogenic high-fat/high-sucrose (HFHS) diet and orally treated with 50 mg/kg of RebA, RebD or vehicle (water) for 12 weeks. An additional group of chow-fed mice treated with the vehicle was included as a healthy reference. At weeks 10 and 12, insulin and oral glucose tolerance tests were performed. Liver lipids content was analyzed. Whole-genome shotgun sequencing was performed to profile the gut microbiota. Bile acids were measured in the feces, plasma, and liver. Liver lipid content and gene expression were analyzed. As compared to the HFHS-vehicle treatment group, mice administered RebD showed a reduced weight gain, as evidenced by decreased visceral adipose tissue weight. Liver triglycerides and cholesterol from RebD-treated mice were lower and lipid peroxidation was decreased. Interestingly, administration of RebD was associated with a significant enrichment of Faecalibaculum rodentium in the gut microbiota and an increased secondary bile acid metabolism. Moreover, RebD decreased the level of lipopolysaccharide-binding protein (LBP). Neither RebA nor RebD treatments were found to impact glucose homeostasis. The daily consumption of two stevia components has no detrimental effects on metabolic health. In contrast, RebD treatment was found to reduce adiposity, alleviate hepatic steatosis and lipid peroxidation, and decrease LBP, a marker of metabolic endotoxemia in a mouse model of diet-induced obesity.


Assuntos
Adiposidade , Diterpenos do Tipo Caurano , Glicosídeos , Resistência à Insulina , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Obesidade/metabolismo , Triglicerídeos , Dieta Hiperlipídica , Sacarose/metabolismo , Ácidos e Sais Biliares/metabolismo , Metabolismo dos Lipídeos
15.
PLoS One ; 19(2): e0298805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394282

RESUMO

Arthropod-borne viruses are major causes of human and animal disease, especially in endemic low- and middle-income countries. Mosquito-borne pathogen surveillance is essential for risk assessment and vector control responses. Sentinel chicken serosurveillance (antibody testing) and mosquito pool screening (by RT-qPCR or virus isolation) are currently used to monitor arbovirus transmission, however substantial time lags of seroconversion and/or laborious mosquito identification and RNA extraction steps sacrifice their early warning value. As a consequence, timely vector control responses are compromised. Here, we report on development of a rapid arbovirus detection system whereby adding sucrose to reagents of loop-mediated isothermal amplification with displaced probes (DP-LAMP) elicits infectious mosquitoes to feed directly upon the reagent mix and expectorate viruses into the reagents during feeding. We demonstrate that RNA from pathogenic arboviruses (West Nile and Dengue viruses) transmitted in the infectious mosquito saliva was detectable rapidly (within 45 minutes) without RNA extraction. Sucrose stabilized viral RNA at field temperatures for at least 48 hours, important for transition of this system to practical use. After thermal treatment, the DP-LAMP could be reliably visualized by a simple optical image sensor to distinguish between positive and negative samples based on fluorescence intensity. Field application of this technology could fundamentally change conventional arbovirus surveillance methods by eliminating laborious RNA extraction steps, permitting arbovirus monitoring from additional sites, and substantially reducing time needed to detect circulating pathogens.


Assuntos
Arbovírus , Culicidae , Vírus da Dengue , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Animais , Humanos , Vírus da Dengue/genética , Saliva , Mosquitos Vetores , RNA , Sacarose
16.
Parasit Vectors ; 17(1): 76, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378683

RESUMO

BACKGROUND: Sugar alcohols, such as erythritol, are low-impact candidates for attractive toxic sugar baits (ATSB) to kill mosquitoes. To determine whether erythritol has a viable future in ATSB formulations, a suite of assays was conducted to diagnose toxicity mechanisms and starvation effects on mortality in Aedes aegypti (L.) as a model system. METHODS: We measured general carbohydrate load, glucosidase levels, and free glucose in intoxicated adult mosquitoes to observe whether sugar digestion was impaired. We assayed the effects of sugar combinations with erythritol on larvae and adults. To measure erythritol effects when mosquitoes were not resource-deprived, additional assays manipulated the prior starvation status. RESULTS: Up to 50,000 ppm of erythritol in water had no effect on larvae within 72 h, but an ammonia spike indicated diuresis in larvae as early as 4 h (F8,44 = 22.50, P < 0.0001) after sucrose/erythritol combinations were added. Adult consumption of erythritol was diuretic regardless of the sugar pairing, while sucrose and erythritol together generated above 80% mortality (F2,273 = 33.30, P < 0.0001) alongside triple the normal excretion (F5,78 = 26.80, P < 0.0004). Glucose and fructose paired individually with erythritol had less mortality, but still double the fecal excretion. When ingesting erythritol-laced meals, less sugar was detected in mosquitoes as compared to after sucrose meals (χ2 = 12.54, df = 1, P = 0.0004). CONCLUSIONS: Data showed that erythritol is a linear competitive inhibitor of α-glucosidase, marking it as a novel class of insecticide in the current research climate. However, the efficacy on larvae was null and not persistent in adult mosquitoes when compared across various starvation levels. Despite significant diuresis, the combined effects from erythritol are not acute enough for vector control programs considering ATSB against mosquitoes.


Assuntos
Aedes , Inseticidas , Animais , Aedes/fisiologia , alfa-Glucosidases , Eritritol/farmacologia , Controle de Mosquitos , Mosquitos Vetores , Açúcares , Carboidratos , Sacarose/farmacologia , Inseticidas/farmacologia , Larva , Glucose , Diurese
17.
Breastfeed Med ; 19(2): 81-90, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38386991

RESUMO

Objectives: To evaluate the efficacy of breastfeeding or feeding of breast milk in reducing blood sampling pain in full-term neonates by comparing with other intervention measures. Methods: Related literature was searched from PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (Central). Only randomized controlled trials (RCTs), which reported the effect of breastfeeding or feeding of breast milk on blood sampling pain in full-term neonates, were eligible. The primary outcome was set as pain score on scales, and the secondary outcomes as physiological and behavioral indicators. The risk of bias in included studies was assessed by the Cochrane Collaboration's tool. Data analysis was performed using RevMan 5.4.1. Main Results: A total of 17 RCTs were included. Breastfeeding showed a stronger effectiveness in reducing blood sampling pain, compared with nonintervention, placebo, mother's holding, breast milk odor, mother's heartbeat, music therapy, skin-to-skin, and Eutectic Mixture of Local Anesthetics ointment. However, the efficacy of glucose or sucrose (12.5%-30% concentration) seems better than breastfeeding. When compared with other interventions, feeding of breast milk yielded different results. Its effect was only stronger than placebo (sterile water or distilled water), massage, or nonintervention. Conclusions: Breastfeeding might be effective for alleviating blood sampling pain in full-term neonates. Its effect is second only to that of glucose/sucrose. The efficacy of feeding of breast milk in reducing blood sampling pain in full-term neonates might not be guaranteed.


Assuntos
Aleitamento Materno , Leite Humano , Feminino , Recém-Nascido , Humanos , Dor/etiologia , Dor/prevenção & controle , Glucose , Sacarose , Água
18.
Appetite ; 195: 107236, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307298

RESUMO

OBJECTIVE: The study aimed to assess potential effects of vaping on individual taste and smell perception in a sample of young adult New Zealanders. DESIGN: This cross-sectional study measured taste and smell perception using intensity and hedonic ratings to two olfactory (i.e., vanillin, methional) and two gustatory stimuli (i.e., sucrose, monosodium glutamate), representing sweet and savoury flavours. Detection sensitivities to sucrose and vanillin were also assessed using a forced choice detection paradigm aligned with the signal detection framework. MANCOVAs were employed to compare sensory perception between groups based on vaping use frequency. Additional regression analyses were conducted to identify potential predictors of intensity and hedonic sensory ratings. SETTING: Participants were recruited from the University of Otago student population and surrounding neighbourhoods of Dunedin, New Zealand in 2023. PARTICIPANTS: The study included 213 university students (98 vapers and 115 non-vapers) RESULTS: We found a significant difference in hedonic ratings for vanillin, indicating a stronger preference among non-vapers. However, no other differences between the two groups were significant. Notably, the use of tobacco and mint flavours were emerged as significant predictors for hedonic responses to the savoury smell and sweet taste stimulus, respectively. No significant differences were observed between groups in the ability to detect weak stimuli. CONCLUSIONS: Our findings suggest that vape use, particularly with specific flavours, may be associated with alterations in hedonic responses to smells. This finding may have potential implications for how vaping affects on food preferences and dietary choices.


Assuntos
Olfato , Percepção Gustatória , Vaping , Humanos , Adulto Jovem , População Australasiana , Benzaldeídos , Estudos Transversais , Aromatizantes , Preferências Alimentares/fisiologia , Nova Zelândia , Olfato/fisiologia , Sacarose , Percepção Gustatória/fisiologia
19.
J Neurochem ; 168(3): 312-327, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317429

RESUMO

To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in associative learning, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks in mice. Sucrose was used as a positive valence unconditioned stimulus (US) and foot shock was used as a negative valence US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general increase in activity in response to the conditioned stimuli (CS). Interestingly, D1- and D2-neurons present distinct changes in activity after sucrose consumption that dynamically evolve throughout learning. During the aversive Pavlovian conditioning, D1- and D2-neurons present an increase in the activity in response to the CS and to the US (shock). Our data support a model in which D1- and D2-neurons are concurrently activated during appetitive and aversive conditioning.


Assuntos
Núcleo Accumbens , Receptores de Dopamina D1 , Animais , Camundongos , Núcleo Accumbens/metabolismo , Receptores de Dopamina D1/metabolismo , Condicionamento Clássico , Neurônios/metabolismo , Aprendizagem da Esquiva/fisiologia , Sacarose/farmacologia
20.
Lett Appl Microbiol ; 77(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38331426

RESUMO

The cariogenicity of Streptococcus mutans relates to its ability to form biofilms on dental surfaces. The aim of this work was to develop a flowcell system compatible with time-lapse confocal microscopy to compare the adhesion and accumulation of S. mutans cells on surfaces in unsupplemented media against media containing sucrose or sucralose (a non-metabolized sweetener) over a short period of time. Fluorescent S. mutans 3209/pVMCherry was suspended in unsupplemented media or media supplemented with 1% sucrose or 1% sucralose and passed through a 3D-printed flowcell system. Flowcells were imaged over 60 minutes using a confocal microscope. Image analysis was performed, including a newly developed object-movement-based method to measure biomass adhesion. Streptococcus mutans 3209/pVMCherry grown in 1% sucrose-supplemented media formed small, dense, relatively immobile clumps in the flowcell system measured by biovolume, surface area, and median object centroid movement. Sucralose-supplemented and un-supplemented media yielded large, loose, mobile aggregates. Architectural metrics and per-object movement were significantly different (P < 0.05) when comparing sucrose-supplemented media to either unsupplemented or sucralose-supplemented media. These results demonstrate the utility of a flowcell system compatible with time-lapse confocal microscopy and image analysis when studying initial biofilm formation and adhesion under different nutritional conditions.


Assuntos
Streptococcus mutans , Edulcorantes , Imagem com Lapso de Tempo , Biofilmes , Sacarose/farmacologia , Microscopia Confocal
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