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1.
Brain Res ; : 149124, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019135

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear. METHODS: We tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK+/- mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model. RESULTS: In this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration. CONCLUSION: BK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.

2.
Sensors (Basel) ; 24(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38894303

RESUMO

The most critical aspect of panorama generation is maintaining local semantic consistency. Objects may be projected from different depths in the captured image. When warping the image to a unified canvas, pixels at the semantic boundaries of the different views are significantly misaligned. We propose two lightweight strategies to address this challenge efficiently. First, the original image is segmented as superpixels rather than regular grids to preserve the structure of each cell. We propose effective cost functions to generate the warp matrix for each superpixel. The warp matrix varies progressively for smooth projection, which contributes to a more faithful reconstruction of object structures. Second, to deal with artifacts introduced by stitching, we use a seam line method tailored to superpixels. The algorithm takes into account the feature similarity of neighborhood superpixels, including color difference, structure and entropy. We also consider the semantic information to avoid semantic misalignment. The optimal solution constrained by the cost functions is obtained under a graph model. The resulting stitched images exhibit improved naturalness. Extensive testing on common panorama stitching datasets is performed on the algorithm. Experimental results show that the proposed algorithm effectively mitigates artifacts, preserves the completeness of semantics and produces panoramic images with a subjective quality that is superior to that of alternative methods.

3.
J Nutr ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38797479

RESUMO

Several organizations have published nutrition guidelines for cancer survivors during and after treatment. This review compared nutrition guidelines for cancer survivors published in the United States for the topics that are covered in the guidelines and evaluated the evidence that these guidelines are based upon. A team of researchers, patient stakeholders, and healthcare providers collectively identified 5 nutrition guidelines for cancer survivors in the United States: the 2022 American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors, the 2018 American Institute for Cancer Research Cancer Nutrition Guide, the 2022 National Cancer Institute Physician Data Query and Eating Hints, the 2024 National Comprehensive Cancer Network Guidelines for Cancer Survivors, and the 2020 American Society for Clinical Oncology Guidelines. The 5 guidelines cover a comprehensive list of nutrition topics but overall promote to follow those recommendations for cancer prevention. This review also evaluated the current evidence from meta-analyses on dietary patterns and intakes of foods and nutrients in relation to survival outcomes among cancer survivors. Although the evidence on dietary patterns is strong, the evidence on most dietary factors is still limited and the current research was primarily conducted among breast and colorectal cancer survivors. Although nutrition recommendations are available for cancer survivors, practical strategies need to be implemented to integrate nutrition into oncology care and help cancer survivors follow these recommendations. Further research is warranted to provide additional evidence on the role of nutrition in the health outcomes of cancer survivors and guide the development of evidence-based nutrition recommendations. The protocol is registered in PROSPERO: CRD42023429240.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38796724

RESUMO

PURPOSE: The present study aimed to identify the optimal design of the unicompartmental femoral component through parameter analysis and stability evaluation. METHODS: A finite element (FE) analysis was applied to analyse and adjust the parameter combinations of the anterior tilt angle of the posterior condyle resection surface, the position of the peg, the length of the peg and the inclination angle of the peg, resulting in 10 different FE models. Setting three knee flexion angles of 8.4° (maximum load state during walking), 40° (maximum load state during stair climbing) and 90° (maximum load state during squatting exercise), quantitatively analysing the micromotion values of the bone-prosthesis interface and defining a weighted scoring formula to evaluate the stability of different FE models. The validity of the FE analysis was verified using the Digital Image Correlation (DIC) device. RESULTS: The errors between the FE analysis and the DIC test at three flexion angles were 5.6%, 1.7% and 11.1%. The 10 different femoral component design models were measured separately. The FE analysis demonstrated that the design with a 0° anterior tilt angle of the posterior condyle resection surface, both pegs placed on the distal resection surface, lengthened 5 mm pegs and a 10° peg inclination angle provided the best stability. CONCLUSION: The current study proposed a method for evaluating the stability of the femoral component design. The optimal intersurface stability design of the unicompartmental femoral component was achieved with two pegs placed on the distal resection surface, a 5-mm peg length increment and a 10° peg inclination. These results might provide a reference for the selection of unicompartmental femoral components in clinical practice and therefore improve the survival rate of future unicompartmental knee arthroplasty. LEVEL OF EVIDENCE: Level III.

5.
FEBS J ; 291(4): 795-813, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37983563

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron (MN) death. Mutation of the superoxide dismutase 1 (SOD1) gene, which results in abnormal protein aggregation, is one of the causes of familial ALS. Autophagic dysfunction occurs in SOD1-G93A mutant mice as the disease progresses, but the etiology of this disease is still unclear. Optineurin (OPTN) is an adaptor that is involved in autophagy and participates in aggrephagy and mitophagy. Previous studies have established that OPTN mutations contribute to diseases such as glaucoma and ALS. However, the function of OPTN in autophagy and mitophagy has not been intensively investigated in models of ALS. In this study, we assessed the beneficial effect of OPTN on autophagy and mitochondrial function by intrathecally injecting adeno-associated virus 9 (AAV9)-OPTN into SOD1-G93A transgenic mice and by administering lentivirus (LV)-OPTN to cells expressing the SOD1-G93A mutant protein. The expression of voltage-dependent anion channel 1 (VDAC1) was increased and autophagy was elevated after OPTN gene therapy, as shown by a lower level of p62 and a higher level of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II. Moreover, using electron microscopy, we observed a hyperpolarized mitochondrial transmembrane potential and reversal of mitochondrial morphological abnormalities. Furthermore, the protein level of TANK-binding kinase 1 (TBK1) was increased, suggesting that mitophagy was increased. Our findings from both animal and cell line studies strongly suggest that OPTN gene therapy is a powerful strategy to increase autophagy and protect mitochondria to prevent the progression of ALS and could be effective in the treatment of ALS.


Assuntos
Esclerose Lateral Amiotrófica , Camundongos , Animais , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/metabolismo , Camundongos Transgênicos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/farmacologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Autofagia/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Animais de Doenças
6.
Immunobiology ; 228(5): 152705, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37459681

RESUMO

The bulge region, a reservoir of multipotent stem cells, is possibly responsible for tumorigenesis. NF-κB-inducing kinase (NIK) is a kinase involved in the activation of the noncanonical NF-κB pathway and exhibits positive staining in tumor cells. However, whether high expression of NIK can result in tumorigenesis has not been reported in published papers. By establishing Nik-coe (Nik-stopF/F crossed with Chat-cre) and Nik-soe (Nik-stopF/F crossed with Sox9-cre) mice, we found that overexpression of Nik in the bulge region of hair follicles induced hair follicle loss and tumorigenesis. Furthermore, RNA sequencing, proteomic and phosphopeptide analyses revealed that multiple cancer pathways are involved in tumor formation. Taken together, these findings indicate that constitutive activation of Nik in the bulge region induces tumorigenesis.


Assuntos
NF-kappa B , Neoplasias , Camundongos , Animais , NF-kappa B/metabolismo , Folículo Piloso/metabolismo , Proteômica , Carcinogênese , Quinase Induzida por NF-kappaB
7.
JAMA Netw Open ; 6(5): e2312530, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37159195

RESUMO

Importance: Pediatric obesity is a growing health care burden. Understanding how the metabolic phenotype of youth with obesity may modify the effect of intestinal fermentation on human metabolism is key to designing early intervention. Objective: To assess whether adiposity and insulin resistance in youth may be associated with colonic fermentation of dietary fibers and its production of acetate, gut-derived hormone secretion, and adipose tissue lipolysis. Design, Setting, and Participants: Cross-sectional study of youths aged 15 to 22 years with body mass index in the 25th to 75th percentile or higher than the 85th percentile for age and sex throughout the New Haven County community in Connecticut. Recruitment, studies, and data collection occurred from June 2018 to September 2021. Youths were assigned to a lean, obese insulin sensitive (OIS), or obese insulin resistant (OIR) group. Data were analyzed from April 2022 to September 2022. Exposure: Participants consumed 20 g of lactulose during a continuous 10-hour sodium d3-acetate intravenous infusion to measure the rate of appearance of acetate in plasma. Main Outcomes and Measures: Plasma was obtained hourly to measure acetate turnover, peptide tyrosine tyrosine (PYY), ghrelin, active glucagon-like peptide 1 (GLP-1), and free fatty acids (FFA). Results: A total of 44 youths participated in the study (median [IQR] age, 17.5 [16.0-19.3] years; 25 [56.8%] were female; 23 [52.3%] were White). Consequent to lactulose ingestion, there was a reduction of plasma FFA, an improvement of adipose tissue insulin sensitivity index, an increase in colonic acetate synthesis, and an anorexigenic response characterized by an increased plasma concentration of PYY and active GLP-1 and a reduction of ghrelin in the subgroups. Compared with the lean and OIS groups, the OIR group showed a less marked median (IQR) rate of acetate appearance (OIR: 2.00 [-0.86 to 2.69] µmol × kg-1 × min-1; lean: 5.69 [3.04 to 9.77] µmol × kg-1 × min-1; lean vs OIR P = .004; OIS: 2.63 [1.22 to 4.52] µmol × kg-1 × min-1; OIS vs OIR P = .09), a blunted median (IQR) improvement of adipose insulin sensitivity index (OIR: 0.043 [ 0.006 to 0.155]; lean: 0.277 [0.220 to 0.446]; lean vs OIR P = .002; OIS: 0.340 [0.048 to 0.491]; OIS vs OIR P = .08), and a reduced median (IQR) PYY response (OIR: 25.4 [14.8 to 36.4] pg/mL; lean: 51.3 [31.6 to 83.3] pg/mL; lean vs OIR P = .002; OIS: 54.3 [39.3 to 77.2] pg/mL; OIS vs OIR P = .011). Conclusions and Relevance: In this cross-sectional study, lean, OIS, and OIR youth demonstrated different associations between colonic fermentation of indigestible dietary carbohydrates and the metabolic response, with OIR youth showing minimal metabolic modifications as compared with the other 2 groups. Trial Registration: ClinicalTrials.gov Identifier: NCT03454828.


Assuntos
Resistência à Insulina , Obesidade Infantil , Criança , Adolescente , Feminino , Humanos , Masculino , Fermentação , Grelina , Estudos Transversais , Lactulose , Insulina , Insulina Regular Humana , Tirosina
8.
J Phys Condens Matter ; 35(25)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990103

RESUMO

The chloridized gallium bismuthide was predicted to be a two-dimensional topological insulator with large topological band gap. It may be beneficial for achieving the quantum spin Hall effect and its related applications at high temperatures. To better understand the quantum transport in topological nanoribbons, we investigated the effect of vacancy on the quantum transport of topological edge states in the armchair chloridized gallium bismuthide nanoribbons by combining density functional theory and nonequilibrium Green's function. The results suggest the vacancies at center are more likely to cause the scattering of topological edge states. The average scattering is insensitive to the enlargement of vacancy along the transport direction. More interestingly, the obvious scattering of topological edge states can only be found at some special energies, and these special energies are distributed quasi-periodically. The quasi-periodic scattering may be used as a kind of fingerprint of vacancies. Our studies may be helpful for the application of topological nanoribbons.

9.
Eur J Pharmacol ; 947: 175633, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863552

RESUMO

Reversible phosphorylation of proteins is an important mechanism that regulates cellular processes, which are precisely regulated by protein kinases and phosphatases. PPM1B is a metal ion-dependent serine/threonine protein phosphatase, which regulates multiple biological functions by targeting substrate dephosphorylation, such as cell cycle, energy metabolism, inflammatory responses. In this review, we summarized the occurrent understandings of PPM1B focused on its regulation of signaling pathways, related diseases, and small-molecular inhibitors, which may provide new insights for the identification of PPM1B inhibitors and the treatment of PPM1B-related diseases.


Assuntos
Fosfoproteínas Fosfatases , Transdução de Sinais , Proteína Fosfatase 2C , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Proteínas Quinases/metabolismo
10.
Obesity (Silver Spring) ; 31(5): 1383-1391, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36694381

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), the most common liver disease among youth with obesity, precedes more severe metabolic and liver diseases. However, the impact of the Sars-CoV-2 global pandemic on the prevalence and severity of NAFLD and the associated metabolic phenotype among youth with obesity is unknown. METHODS: Participants were recruited from the Yale Pediatric Obesity Clinic during the Sars-CoV-2 global pandemic (August 2020 to May 2022) and were compared with a frequency-matched control group of youth with obesity studied before the Sars-CoV-2 global pandemic (January 2017 to November 2019). Glucose metabolism differences were assessed during an extended 180-minute oral glucose tolerance test. Magnetic resonance imaging-derived proton density fat fraction (PDFF) was used to determine intrahepatic fat content in those with NAFLD (PDFF ≥ 5.5). RESULTS: NAFLD prevalence increased in participants prior to (36.2%) versus during the Sars-CoV-2 pandemic (60.9%), with higher PDFF values observed in participants with NAFLD (PDFF ≥ 5.5%) during versus before the pandemic. An increase in visceral adipose tissue and a hyperresponsiveness in insulin secretion during the oral glucose tolerance test were also observed. CONCLUSIONS: Hepatic health differences were likely exacerbated by environmental and behavioral changes associated with the pandemic, which are critically important for clinicians to consider when engaging in patient care to help minimize the future risk for metabolic perturbations.


Assuntos
COVID-19 , Hepatopatia Gordurosa não Alcoólica , Estados Unidos/epidemiologia , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , SARS-CoV-2 , Pandemias , COVID-19/epidemiologia , COVID-19/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Obesidade/epidemiologia , Obesidade/patologia , Imageamento por Ressonância Magnética
11.
Brain Res ; 1798: 148155, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343723

RESUMO

Interferon-regulatory factor 5 (IRF5) participates in the regulation of apoptosis, affects the phenotype of inflammatory macrophages and plays an essential role in the inflammatory response. However, the role of IRF5 in the progression of amyotrophic lateral sclerosis (ALS) remains largely unknown. Here, we show that IRF5 mainly accumulated in the nucleus in cells expressing the truncated 25 kD C-terminal fragments of TDP-43 (TDP-25, named TDP-25 cells hereafter). IRF5 knockdown using a lentivirus carrying an shRNA in TDP-25 cells exerted a protective effect and reduced the level of the apoptosis-related protein cleaved caspase-9 and the cell cycle arrest protein p21, while increasing the expression of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its target molecule glutamate-cysteine ligase modulatory subunit (GCLM). Furthermore, IRF5-knockdown cells showed improved mitochondrial swelling and cristae dilation. In addition, we found that IRF5 mediated neuronal injury partly through the negative regulation of TANK-binding kinase 1 (TBK1). These data indicate that the loss of IRF5 in TDP-25 cells exerts a protective effect mainly by inhibiting apoptosis, regulating cell cycle arrest and alleviating oxidative stress.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Estresse Oxidativo/fisiologia , Proteínas de Ciclo Celular/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Fragmentos de Peptídeos/metabolismo
12.
Polymers (Basel) ; 14(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080628

RESUMO

To investigate an environmentally benign stabilizer for coarse-grained soil in southeast Tibet, poly (vinyl alcohol) (PVA) and silica fume were used to improve the geotechnical properties of coarse-grained soil. Unconfined compressive strength (UCS) and wet-dry cycle tests were conducted on prepared samples to evaluate the effect of the additive content and curing age on the strength and durability of coarse-grained soil. The results reveal that the UCS of the samples increased with the additive content of PVA solution and the curing age. The optimal value for the additive content of PVA solution and the curing age is 12% and 7 days, respectively. With the optimal PVA solution content, the PVA solution combined with silica fume stabilizer exhibited better reinforcement compared with pristine PVA. The UCS of the samples stabilized by PVA solution and silica fume increased depending on the curing age, and plateaued after 14 days. Samples with 12% PVA solution and 6% silica fume achieved a satisfactory UCS of 1543.17 kPa after curing for 28 days. As the number of wet-dry cycles increased, the UCS of the samples stabilized by the PVA solution and silica fume exhibited an upward trend during the first three wet-dry cycles, owing to the filling of pores by the gel produced by the silica fume, but began to decline as the number of wet-dry cycles increased. All samples retained a high UCS value after 10 wet-dry cycles compared with the samples that were not subjected to wet-dry cycles.

13.
Materials (Basel) ; 15(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36013746

RESUMO

Materials with violent hydration reaction such as cement are used to solidify sandy soil slopes, which will cause destructive damage to the ecology of the slopes. In this paper, polyvinyl alcohol (PVA) and activated magnesium oxide (MgO) are used to improve sandy soil, and the effects of the dosage and curing age of modifiers on the mechanical properties of solidified sandy soil are studied. The dry-wet durability of the composite improved sandy soil is analyzed using a dry-wet cycle test, and the improvement mechanism of PVA and activated magnesium oxide is revealed using an electron microscope. The results show that the curing effect of polyvinyl alcohol and activated magnesium oxide on sand particles is better than that of polyvinyl alcohol alone. The compressive strength of improved soil samples increases with the increase of curing time, and magnesium oxide as an improved material needs appropriate reaction conditions to give full play to its role. The compressive strength of composite improved samples increases first and then decreases during the dry-wet cycle. Through the observation of microstructure, it can be seen that the cementing material wraps and connects the sand particles, and the cementing material of the sample after the dry-wet cycle develops more completely; if the magnesium oxide content is high, cracks may appear inside the sample.

14.
Int J Colorectal Dis ; 37(9): 2021-2029, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35997991

RESUMO

OBJECTIVES: To evaluate the value of preoperative CT energy spectrum imaging in detecting lymph node metastasis of colorectal cancer. METHODS: From September 2019 to November 2021, a retrospective study was performed for the eighty-two patients with colorectal cancer through preoperative colonoscopy or surgical pathology confirmed in our hospital. Based on the lymph node metastasis status, these cases were divided into the metastasis and non-metastasis groups. GE Revolution CT scanner was used to scan the patients with energy spectrum imaging, it measured and recorded the single-energy CT values from 40 to 140 keV and various energy spectrum parameters of lymph nodes around the lesions in the arterial and venous phases, and statistically analyze the above indices. RESULTS: In the arterial and venous phases: the single-energy CT values of 40-140 keV in the non-metastatic group were higher than those in the metastatic group (all P < 0.05); the parameter values of IC (iodine concentration), NIC (normalized iodine concentration), λ (the slope of the energy spectrum curve), and Eff-Z (effective-Z) in the non-metastatic group were higher than those in the metastatic group (all P < 0.05). Further evaluation of ROC curve showed that the higher AUC (area under curve) of the single-energy CT value of 50 keV in the arterial phase was 0.889, among the energy spectrum parameters of IC, NIC, λ, and Eff-Z, the NIC had the better diagnostic efficiency and the AUC of the NIC was 0.873, the highest AUC of the combination of NIC and λ was 0.885 when the energy spectrum parameters were combined. The higher AUC of the single-energy CT value of 60 keV in the venous phase was 0.853, among the energy spectrum parameters of IC, NIC, λ, and Eff-Z, the λ had the better diagnostic efficiency and the AUC of the λ was 0.822, the higher AUC of the combination of NIC, λ, and Eff-Z was 0.840 when the energy spectra were combined. CONCLUSIONS: Parameters of energy spectrum CT imaging can effectively evaluate whether lymph nodes have metastases, and provide favorable imaging diagnosis basis for the range and the number of lymph nodes to be cleaned during clinical operation and can evaluate the prognosis of patients. It is worthy of clinical recommendation.


Assuntos
Neoplasias Colorretais , Iodo , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estudos Retrospectivos , Tomografia Computadorizada Espiral , Tomografia Computadorizada por Raios X/métodos
15.
Hepatol Commun ; 6(8): 1962-1974, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35344283

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is often the precursor for more serious liver conditions such as nonalcoholic steatohepatitis and cirrhosis. Although the gut microbiome has been implicated in the development of NAFLD, the strong association of obesity with NAFLD and its effect on microbiome structure has made interpreting study outcomes difficult. In the present study, we examined the taxonomic and functional differences between the microbiomes of youth with obesity and with and without NAFLD. Shotgun metagenome sequencing was performed to profile the microbiomes of 36 subjects, half of whom were diagnosed with NAFLD using abdominal magnetic resonance imaging. Beta diversity analysis showed community-wide differences between the groups (p = 0.002). Specific taxonomic differences included increased relative abundances of the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009), and a decrease of Bacteroides thetaiotamicron (p = 0.0002), in the NAFLD group as compared with the non-NAFLD group. At the phylum level, Bacteroidetes (p < 0.0001) was decreased in the NAFLD group. Functionally, branched-chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways had increased relative abundances in the NAFLD group along with numerous energy use pathways, including pyruvate fermentation to acetate (p = 0.01318). Conclusion: Community-wide differences were noted based on NAFLD status, and individual bacterial species along with specific metabolic pathways were identified as potential drivers of these differences. The results of the present study support the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Bactérias/genética , Microbioma Gastrointestinal/genética , Humanos , Redes e Vias Metabólicas/genética , Metagenômica , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/complicações
16.
Diabetes Obes Metab ; 24(7): 1267-1276, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35297549

RESUMO

AIM: To examine the determinants and metabolic impact of the reduction in fasting and postload insulin levels after a low n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio diet in obese youth. MATERIALS AND METHODS: Insulin secretion and clearance were assessed by measuring and modelling plasma insulin and C-peptide in 17 obese youth who underwent a nine-point, 180-minute oral glucose tolerance test (OGTT) before and after a 12-week, eucaloric low n-6:n-3 polyunsaturated fatty acid (PUFA) ratio diet. Hepatic fat content was assessed by repeated abdominal magnetic resonance imaging. RESULTS: Insulin clearance at fasting and during the OGTT was significantly increased after the diet, while body weight, glucose levels, absolute and glucose-dependent insulin secretion, and model-derived variables of ß-cell function were not affected. Dietary-induced changes in insulin clearance positively correlated with changes in whole-body insulin sensitivity and ß-cell glucose sensitivity, but not with changes in hepatic fat. Subjects with greater increases in insulin clearance showed a worse metabolic profile at enrolment, characterized by impaired insulin clearance, ß-cell glucose sensitivity, and glucose tolerance, and benefitted the most from the diet, achieving greater improvements in glucose-stimulated hyperinsulinaemia, insulin resistance, and ß-cell function. CONCLUSIONS: We showed that a 12-week low n-6:n-3 PUFA ratio diet improves hyperinsulinaemia by increasing fasting and postload insulin clearance in obese youth, independently of weight loss, glucose concentrations, and insulin secretion.


Assuntos
Ácidos Graxos Ômega-3 , Hiperinsulinismo , Resistência à Insulina , Adolescente , Glicemia/metabolismo , Dieta , Glucose , Humanos , Hiperinsulinismo/etiologia , Insulina/metabolismo , Resistência à Insulina/fisiologia , Insulina Regular Humana , Obesidade/complicações , Obesidade/metabolismo
17.
Nutr Diabetes ; 12(1): 9, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35194014

RESUMO

OBJECTIVE: Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. In animal models, it has been noted that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children. DESIGN: In the current study, we explored the association of circulating plasma concentrations of GDF15 with NAFLD in youth with overweight/obesity, and whether changes in plasma concentrations in GDF15 parallel the changes in intrahepatic fat content (HFF%) over time. METHODS: Plasma GDF15 concentrations were measured by ELISA in 175 youth with overweight/obesity who underwent an oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) to assess intrahepatic, visceral, and subcutaneous fat. Baseline fasting GDF15 concentrations were measured in twenty-two overweight/obese youth who progressed (n = 11) or regressed (n = 11) in HFF% by more than 30% of original over a 2-year period. RESULTS: Youth with NAFLD had significantly higher plasma concentrations of GDF15 than those without NAFLD, independent of age, sex, ethnicity, BMI z-score (BMIz), and visceral fat (P = 0.002). During the OGTT, there was a decline in plasma GDF15 concentrations from 0 to 60 min, but GDF15 concentrations returned to basal levels by the end of the study. There was a statistically significant association between change in HFF% and change in GDF15 (P = 0.008; r2 = 0.288) over ~2 years of follow-up. CONCLUSIONS: These data suggest that plasma GDF15 concentrations change with change in intrahepatic fat content in youth with overweight/obesity and may serve as a biomarker for NAFLD in children.


Assuntos
Fator 15 de Diferenciação de Crescimento , Hepatopatia Gordurosa não Alcoólica , Obesidade , Sobrepeso , Adolescente , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Sobrepeso/complicações
18.
Nutrients ; 13(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068066

RESUMO

Only a few studies primarily examined the associations between starchy vegetables (other than potatoes) and metabolic syndrome (MetS). We aimed to evaluate the association between starchy vegetables consumption and MetS in a population-based sample of Costa Rican adults. We hypothesized that a higher overall intake of starchy vegetables would not be associated with higher MetS prevalence. In this cross-sectional study, log-binomial regression models were used to estimate prevalence ratios (PRs) of MetS across quintiles of total, unhealthy, healthy starchy vegetables, and individual starchy vegetables (potatoes, purple sweet potatoes, etc.), among 1881 Costa Rican adults. Least square means and 95% confidence intervals (CIs) from linear regression models were estimated for each MetS component by categories of starchy vegetable variables. Higher intakes of starchy vegetables were associated with a higher prevalence of MetS in crude models, but no significant trends were observed after adjusting for confounders. A significant inverse association was observed between total starchy and healthy starchy vegetables consumption and fasting blood glucose. In this population, starchy vegetables might be part of a healthy dietary pattern.


Assuntos
Síndrome Metabólica/etiologia , Amido/efeitos adversos , Verduras/efeitos adversos , Glicemia/análise , Estudos de Casos e Controles , Costa Rica/epidemiologia , Estudos Transversais , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Solanum tuberosum/efeitos adversos
19.
J Phys Condens Matter ; 33(32)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34077919

RESUMO

Stanene has been predicted to be a two-dimensional topological insulator, providing an ideal platform for the realization of quantum spin Hall effect even at room temperature. Based on first-principles calculations, we studied the topological edge states in zigzag chlorinated stanene nanoribbon. From our calculations, dual Dirac points can be found near Fermi level. One Dirac point is localized at the edges and emerges in a narrow nanoribbon, while another is widespread and can only be found in a wide nanoribbon due to the coupling of two opposite edges. At the localized Dirac point, there is an interesting odd-even oscillated energy gap with the change of the width of nanoribbon. The energy gaps at both Dirac points and the coupling of two opposite edges can be modified by edge adsorption. Asymmetric adsorption of two edges was also discussed. Our calculations may be helpful for the potential applications of tin-based topological nanoribbons in nanodevices.

20.
Cell Death Dis ; 12(2): 196, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608505

RESUMO

Fibroblast growth factor 9 (FGF9) has long been assumed to modulate multiple biological processes, yet very little is known about the impact of FGF9 on neurodevelopment. Herein, we found that loss of Fgf9 in olig1 progenitor cells induced epilepsy in mice, with pathological changes in the cortex. Then depleting Fgf9 in different neural populations revealed that epilepsy was associated with GABAergic neurons. Fgf9 CKO in GABAergic neuron (CKOVGAT) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKOVGAT mice caused neuronal apoptosis and decreased GABA expression, leading to a GABA/Glu imbalance and epilepsy. The adenylate cyclase/cyclic AMP and ERK signaling pathways were activated in this process. Recombinant FGF9 proteoliposomes could significantly decrease the number of seizures. Furthermore, the decrease of FGF9 was commonly observed in serum of epileptic patients, especially those with focal seizures. Thus, FGF9 plays essential roles in GABAergic neuron survival and epilepsy pathology, which could serve as a new target for the treatment of epilepsy.


Assuntos
Córtex Cerebral/metabolismo , Epilepsia/metabolismo , Fator 9 de Crescimento de Fibroblastos/deficiência , Neurônios GABAérgicos/metabolismo , Células-Tronco Neurais/metabolismo , Adenilil Ciclases/metabolismo , Adulto , Animais , Anticonvulsivantes/farmacologia , Apoptose , Estudos de Casos e Controles , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Epilepsia/patologia , Epilepsia/fisiopatologia , Epilepsia/prevenção & controle , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fator 9 de Crescimento de Fibroblastos/sangue , Fator 9 de Crescimento de Fibroblastos/genética , Fator 9 de Crescimento de Fibroblastos/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/patologia , Predisposição Genética para Doença , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Adulto Jovem
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