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1.
Development ; 149(16)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35899600

RESUMO

Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remain elusive. This study highlights the regulatory role of cytidine triphosphate synthase (CTPsyn) in collective border cell migration through regulating the asymmetrical distribution of PIP2. We demonstrated that border cell clusters containing mutant CTPsyn cells suppressed migration. CTPsyn was co-enriched with Actin at the leading edge of the Drosophila border cell cluster where PIP2 was enriched, and this enrichment depended on the CTPsyn activity. Genetic interactions of border cell migration were found between CTPsyn mutant and genes in PI biosynthesis. The CTPsyn reduction resulted in loss of the asymmetric activity of endocytosis recycling. Also, genetic interactions were revealed between components of the exocyst complex and CTPsyn mutant, indicating that CTPsyn activity regulates the PIP2-related asymmetrical exocytosis activity. Furthermore, CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model in which CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Carbono-Nitrogênio Ligases , Movimento Celular/genética , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo
2.
Biogerontology ; 24(3): 391-401, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36802043

RESUMO

Non-alcoholic fatty liver disease is associated with ageing, and impaired mitochondrial homeostasis is the main cause for hepatic ageing. Caloric restriction (CR) is a promising therapeutic approach for fatty liver. The purpose of the present study was to investigate the possibility of early-onset CR in decelerating the progression of ageing-related steatohepatitis. The putative mechanism associated with mitochondria was further determined. C57BL/6 male mice at 8 weeks of age were randomly assigned to one of three treatments: Young-AL (AL, ad libitum), Aged-AL, or Aged-CR (60% intake of AL). Mice were sacrificed when they were 7 months old (Young) or 20 months old (Aged). Aged-AL mice displayed the greatest body weight, liver weight, and liver relative weight among treatments. Steatosis, lipid peroxidation, inflammation, and fibrosis coexisted in the aged liver. Mega mitochondria with short, randomly organized crista were noticed in the aged liver. The CR ameliorated these unfavourable outcomes. The level of hepatic ATP decreased with ageing, but this was reversed by CR. Ageing caused a decrease in mitochondrial-related protein expressions of respiratory chain complexes (NDUFB8 and SDHB) and fission (DRP1), but an increase in proteins related to mitochondrial biogenesis (TFAM), and fusion (MFN2). CR reversed the expression of these proteins in the aged liver. Both Aged-CR and Young-AL revealed a comparable pattern of protein expression. To summarize, this study demonstrated the potential of early-onset CR in preventing ageing-associated steatohepatitis, and maintaining mitochondrial functions may contribute to CR's protection during hepatic ageing.


Assuntos
Restrição Calórica , Fígado Gorduroso , Camundongos , Masculino , Animais , Camundongos Endogâmicos C57BL , Mitocôndrias , Fígado Gorduroso/prevenção & controle , Envelhecimento/metabolismo , Homeostase
3.
J Cell Sci ; 133(9)2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32184263

RESUMO

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.


Assuntos
Carbono-Nitrogênio Ligases , Histidina , Animais , Citidina Trifosfato , Histidina/genética , Queratinas
4.
PLoS Biol ; 17(3): e2007097, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30883547

RESUMO

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Memória/fisiologia , Receptores de Serotonina/metabolismo , Ácido 3-Hidroxibutírico/sangue , Animais , Western Blotting , Corticosterona/sangue , Eletrofisiologia , Teste de Tolerância a Glucose , Hipocampo/citologia , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Receptores de Serotonina/genética , Serotonina/sangue , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
5.
Clin Nephrol ; 97(4): 206-214, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35102817

RESUMO

BACKGROUND: A big concern for continuous ambulatory peritoneal dialysis (CAPD) is dialysis adequacy in anuric patients. Some studies have even suggested that CAPD patients should be transferred to hemodialysis when they become anuric in order to achieve adequate dialysis. In the present study, we tried to find out whether anuric patients can maintain nitrogen balance with standard or even lower dialysis dose. MATERIALS AND METHODS: This was a cross-sectional single-center study. Fifteen anuric CAPD patients were selected. Their 3-day dietary records were reviewed by a dedicated dietitian to calculate their energy, protein, and nitrogen intake (NI). Nitrogen removal (NR) from urine and dialysate was measured by Kjeldahl technique. Fluid status was evaluated by bioimpedance analysis. Subjective global nutritional assessment was used to evaluate nutritional status. RESULTS: Among the 15 patients, 9 males and 6 females, mean age was 63.80 (31 - 77) years, dialysis duration 39.76 (6 - 127) months, body weight 58.70 ± 9.86 kg, and height 160.20 ± 7.93 cm. The mean dietary protein intake was 43.28 ± 7.57 g/day (0.80 ± 0.15 g/kg/d), total Kt/V was 1.59 ± 0.32 with dialysis dose of 7,904.00 ± 1,481.79 mL. However, they achieved neutral nitrogen balance (NI 6.92 ± 1.21 g/d vs. NR 6.83 ± 1.36 g/d, N balance 0.09 ± 1.00 g/d). All of them maintained good nutritional status (SGA "A", serum albumin 39.67 ± 3.58 g/L), and no symptom of nitrogen retention (serum urea 20.49 ± 3.06 mmol/L). Meanwhile, they achieved good volume control with a slightly low total fluid removal (704.00 ± 293.21 mL/d). CONCLUSION: Our study suggested that anuric patients (even with low Kt/V) can achieve nitrogen balance and stay well-nourished with appropriate dietary protein intake.


Assuntos
Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Estudos Transversais , Proteínas Alimentares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrogênio/metabolismo , Diálise Peritoneal/métodos , Ureia
6.
J Neuroinflammation ; 18(1): 110, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975618

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. METHODS: Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. RESULTS: Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. CONCLUSIONS: Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Encefalomielite Autoimune Experimental/patologia , Guaiacol/análogos & derivados , Células Th1/imunologia , Células Th17/imunologia , Animais , Anti-Inflamatórios/farmacologia , Diferenciação Celular/imunologia , Encefalomielite Autoimune Experimental/imunologia , Feminino , Guaiacol/farmacologia , Inflamação/imunologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos
7.
J Neuroinflammation ; 17(1): 138, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349768

RESUMO

BACKGROUND: Inflammatory stimuli induce immunoresponsive gene 1 (IRG1) expression that in turn catalyzes the production of itaconate from the tricarboxylic acid cycle. Itaconate has recently emerged as a regulator of immune cell functions, especially in macrophages. Studies show that itaconate is required for the activation of anti-inflammatory transcription factor Nrf2 by LPS in mouse and human macrophages, and LPS-activated IRG1-/- macrophages that lack endogenous itaconate production exhibit augmented inflammatory responses. Moreover, dimethyl itaconate (DMI), an itaconate derivative, inhibits IL-17-induced IκBς activation in keratinocytes and modulates IL-17-IκBς pathway-mediated skin inflammation in an animal model of psoriasis. Currently, the effect of itaconate on regulating macrophage functions and peripheral inflammatory immune responses is well established. However, its effect on microglia (MG) and CNS inflammatory immune responses remains unexplored. Thus, we investigated whether itaconate possesses an immunomodulatory effect on regulating MG activation and CNS inflammation in animal models of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). METHODS: Chronic C57BL/6 EAE was induced followed by DMI treatment. The effect of DMI on disease severity, blood-brain barrier (BBB) disruption, MG activation, peripheral Th1/Th17 differentiation, and the CNS infiltration of Th1/Th17 cells in EAE was determined. Primary MG was cultured to study the effect of DMI on MG activation. Relapsing-remitting SJL/J EAE was induced to assess the therapeutic effect of DMI. RESULTS: Our results show DMI ameliorated disease severity in the chronic C57BL/6 EAE model. Further analysis of the cellular and molecular mechanisms revealed that DMI mitigated BBB disruption, inhibited MMP3/MMP9 production, suppressed microglia activation, inhibited peripheral Th1/Th17 differentiation, and repressed the CNS infiltration of Th1 and Th17 cells. Strikingly, DMI also exhibited a therapeutic effect on alleviating severity of relapse in the relapsing-remitting SJL/J EAE model. CONCLUSIONS: We demonstrate that DMI suppresses neuroinflammation and ameliorates disease severity in EAE through multiple cellular and molecular mechanisms, suggesting that DMI can be developed as a novel therapeutic agent for the treatment of MS/EAE through its immunomodulatory and anti-inflammatory properties.


Assuntos
Anti-Inflamatórios/farmacologia , Encefalomielite Autoimune Experimental/patologia , Inflamação/patologia , Medula Espinal/efeitos dos fármacos , Succinatos/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Medula Espinal/patologia
8.
Ann Surg Oncol ; 27(8): 3041-3051, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32040700

RESUMO

BACKGROUND: This meta-analysis aimed to investigate the value of preoperative sarcopenia in predicting complications after esophagectomy. Clinicopathologic characteristics of sarcopenia patients, which may support sarcopenia management, also were studied. METHODS: This study searched for articles describing an association between sarcopenia and short-term outcomes after esophagectomy using PubMed, EMBASE, and the Cochrane Library. Mantel-Haenszel and inverse variance models were used for the meta-analyses of end points. RESULTS: The meta-analysis included 14 studies comprising a total of 2387 patients. Sarcopenia was significantly associated with advanced age (weighted mean difference [WMD], 3.48; 95% confidence interval [CI], 2.22-4.74), lower body mass index (WMD - 2.22; 95% CI - 2.65 to - 1.79), squamous cell carcinoma (odds ratio [OR], 2.78; 95% CI 1.72-4.47), advanced clinical tumor stage (OR 1.65; 95% CI 1.28-2.15), and neoadjuvant therapy (OR 1.87; 95% CI 1.38-2.53). The sarcopenia patients showed lower preoperative albumin levels (WMD - 0.11; 95% CI - 0.19 to - 0.04) than the nonsarcopenia patients. Sarcopenia was significantly predictive of pneumonia (OR 2.58; 95% CI 1.75-3.81) and overall complications (OR 1.52; 95% CI 1.07-2.15) after esophagectomy. The sarcopenia patients also showed nonsignificant increases in the risks of anastomotic leakage (OR 1.29; 95% CI 0.99-1.67), vocal cord palsy (OR 2.03; 95% CI 0.89-4.64), and major complications (≥ Clavien-Dindo grade III; OR 1.30; 95% CI 0.95-1.79) but not increased operation time, blood loss, or mortality. CONCLUSIONS: Preoperative sarcopenia assessment showed considerable potential for predicting postoperative complications for esophageal cancer patients. To realize this potential, more effective diagnostic criteria and severity classifications for sarcopenia are warranted.


Assuntos
Neoplasias Esofágicas , Sarcopenia , Fístula Anastomótica , Carcinoma de Células Escamosas , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/etiologia , Sarcopenia/complicações
9.
FASEB J ; 32(7): 3870-3877, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29475396

RESUMO

Appropriate sexual selection or individual sexual attractiveness is closely associated with the reproductive success of a species. Here, we report that young male flies exhibit innate courtship preference for female flies that are raised on higher-yeast diets and that have greater body weight and fecundity, but reduced locomotor activity and shortened lifespan. Male flies discriminate among females that have been fed diets that contain 3 different yeast concentrations-1, 5, and 20% yeast- via gustatory, but not visual or olfactory, perception. Female flies that are raised on higher-yeast diets exhibit elevated expression levels of Drosophila insulin-like peptides (di lps), and we demonstrate that hypomorphic mutations of di lp2, 3, 5 or foxo, as well as oenocyte-specific gene disruption of the insulin receptor, all abolish this male courtship preference for high yeast-fed females. Moreover, our data demonstrate that disrupted di lp signaling can alter the expression profile of some cuticular hydrocarbons (CHCs) in female flies, and that genetic inhibition of an enzyme involved in the biosynthesis of CHCs in oenocytes, elongase F, also eliminates the male courtship preference. Together, our findings provide mechanistic insights that link female reproductive potential to sexual attractiveness, thereby encouraging adaptive mating and optimal reproductive success.-Lin, W.-S., Yeh, S.-R., Fan, S.-Z., Chen, L.-Y., Yen, J.-H., Fu, T.-F., Wu, M.-S., Wang, P.-Y. Insulin signaling in female Drosophila links diet and sexual attractiveness.


Assuntos
Dieta , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Preferência de Acasalamento Animal , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Transdução de Sinais
11.
Brain Behav Immun ; 70: 76-87, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29604346

RESUMO

Multiple sclerosis (MS) is an autoimmune disorder characterized by the central nervous system (CNS) infiltration of myelin-specific pathogenic T cells followed by brain inflammation in association with demyelination. Similarly, experimental autoimmune encephalomyelitis (EAE), the animal model of MS, also exhibits increased CNS infiltration of pathogenic T cells, including Th1 and Th17, leading to detrimental effects of neuroinflammation and demyelination. We previously reported that 3H-1,2-dithiole-3-thione (D3T), the structurally-simplest of the sulfur-containing dithiolethiones, exerted a promising therapeutic effect in EAE. In the current study we report that 5-Amino-3-thioxo-3H-(1,2)dithiole-4-carboxylic acid ethyl ester (ACDT), a substituted derivative of D3T, exhibits anti-inflammatory properties in EAE. ACDT, administered post immunization, delayed disease onset and reduced disease severity in chronic C57BL/6 EAE, and ACDT, administered during disease remission, suppressed disease relapse in relapsing-remitting SJL/J EAE. Further analysis of the cellular and molecular mechanisms underlying the protective effects of ACDT in EAE revealed that ACDT inhibited pathogenic T cell infiltration, suppressed microglia activation, repressed neurotoxic A1 astrocyte generation, lessened blood-brain barrier disruption, and diminished MMP3/9 production in the CNS of EAE. In summary, we demonstrate that ACDT suppresses neuroinflammation and ameliorates disease severity in EAE through multiple cellular mechanisms. Our findings suggest the potential of developing ACDT as a novel therapeutic agent for the treatment of MS/EAE.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Tionas/uso terapêutico , Tiofenos/uso terapêutico , Animais , Sistema Nervoso Central , Modelos Animais de Doenças , Feminino , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Bainha de Mielina , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Tionas/síntese química , Tionas/farmacologia , Tiofenos/síntese química , Tiofenos/farmacologia
12.
Development ; 141(3): 563-73, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24401369

RESUMO

The nutritional environment is crucial for Drosophila oogenesis in terms of controlling hormonal conditions that regulate yolk production and the progress of vitellogenesis. Here, we discovered that Drosophila Endophilin B (D-EndoB), a member of the endophilin family, is required for yolk endocytosis as it regulates membrane dynamics in developing egg chambers. Loss of D-EndoB leads to yolk content reduction, similar to that seen in yolkless mutants, and also causes poor fecundity. In addition, mutant egg chambers exhibit an arrest at the previtellogenic stage. D-EndoB displayed a crescent localization at the oocyte posterior pole in an Oskar-dependent manner; however, it did not contribute to pole plasm assembly. D-EndoB was found to partially colocalize with Long Oskar and Yolkless at the endocytic membranes in ultrastructure analysis. Using an FM4-64 dye incorporation assay, D-EndoB was also found to promote endocytosis in the oocyte. When expressing the full-length D-endoB(FL) or D-endoB(ΔSH3) mutant transgenes in oocytes, the blockage of vitellogenesis and the defect in fecundity in D-endoB mutants was restored. By contrast, a truncated N-BAR domain of the D-EndoB only partially rescued these defects. Taken together, these results allow us to conclude that D-EndoB contributes to the endocytic activity downstream of Oskar by facilitating membrane dynamics through its N-BAR domain in the yolk uptake process, thereby leading to normal progression of vitellogenesis.


Assuntos
Aciltransferases/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Gema de Ovo/citologia , Endocitose , Oócitos/citologia , Aciltransferases/química , Aciltransferases/genética , Animais , Membrana Celular/metabolismo , Polaridade Celular/genética , RNA Helicases DEAD-box/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/ultraestrutura , Gema de Ovo/metabolismo , Feminino , Fertilidade/genética , Perfilação da Expressão Gênica , Mutação/genética , Oócitos/metabolismo , Oócitos/ultraestrutura , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Transporte Proteico , Transdução de Sinais/genética
13.
Clin Nephrol ; 87 (2017)(2): 84-92, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28074773

RESUMO

OBJECTIVE: Due to limited economic conditions, we tried to provide "fitted" dialysis doses instead of the doses recommended by the international guidelines to the individual patients. In the present cross-sectional study, we studied the dialysis adequacy and nutritional status of 5 peritoneal dialysis patients who had a low dialysis dose (2 bags, 4,000 mL/day). METHODS: The 3-day dietary records were reviewed to calculate patients' energy, protein, and nitrogen intake (NI). The nitrogen removal (NR) from urine and dialysate was measured by Kjeldahl technique. Fecal nitrogen was estimated as 0.0155 g/kg/day. Subjective global nutritional assessment was used to evaluate the nutritional status. RESULTS: Among the 5 patients, 1 male and 4 female, mean age was 59 (42 - 81) years, dialysis duration 43 (33 - 74) months, body weight 51.05 ± 2.53 kg. The mean dietary protein intake was 0.66 g/kg/day, total weekly Kt/v was 1.25 (residual kidney Kt/v was 0.09), and total daily fluid removal was 699 mL. However, they achieved lower-level neutral nitrogen balance (NI 5.26 ± 0.93 g/day vs. NR 5.33 ± 0.81 g/day, N balance -0.07 ± 0.60 g/day). All of them maintained good nutritional status (SGA "A") without symptoms of nitrogen retention (serum urea 22 ± 4.18 mmol/L). CONCLUSIONS: Lower dialysis dose with lower daily protein intake can achieve a lower-level nitrogen balance and does not lead to malnutrition. It may be an effective approach to solve the dialysis problem for the economically week population in China, especially for people with a smaller body size with lower transport membrane.
.


Assuntos
Dieta com Restrição de Proteínas , Proteínas Alimentares/administração & dosagem , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Nitrogênio/metabolismo , Diálise Peritoneal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Nitrogênio da Ureia Sanguínea , China , Estudos Transversais , Soluções para Diálise , Feminino , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Ureia/sangue
14.
Brain Behav Immun ; 57: 173-186, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27013356

RESUMO

3H-1,2-dithiole-3-thione (D3T), the simplest member of the sulfur-containing dithiolethiones, is found in cruciferous vegetables, and has been previously reported to be a potent inducer of antioxidant genes and glutathione biosynthesis by activation of the transcription factor Nrf2. D3T is a cancer chemopreventive agent and possesses anti-inflammatory properties. Although D3T has been shown to protect against neoplasia, the effect of D3T in the autoimmune inflammatory disease multiple sclerosis/experimental autoimmune encephalomyelitis (EAE) is unknown. The present study is the first report of the therapeutic effect of D3T in EAE. Our results show D3T, administered post immunization, not only delays disease onset but also dramatically reduces disease severity in EAE. Strikingly, D3T, administered post disease onset of EAE, effectively prevents disease progression and exacerbation. Mechanistic studies revealed that D3T suppresses dendritic cell activation and cytokine production, inhibits pathogenic Th1 and Th17 differentiation, represses microglia activation and inflammatory cytokine expression, and promotes microglia phase II enzyme induction. In summary, these results indicate that D3T affects both innate and adaptive immune cells, and the protective effect of D3T in EAE might be attributed to its effects on modulating dendritic cell and microglia activation and pathogenic Th1/Th17 cell differentiation.


Assuntos
Anti-Inflamatórios/farmacologia , Células Dendríticas/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Microglia/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Tionas/farmacologia , Tiofenos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tionas/administração & dosagem , Tiofenos/administração & dosagem
15.
Chin J Physiol ; 57(6): 350-7, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25575524

RESUMO

The E3 ubiquitin-protein ligase Casitas B-lineage lymphoma protein (Cbl) negatively regulates epidermal growth factor receptor (EGFR) signaling pathway in many organisms, and has crucial roles in cell growth, development and human pathologies, including lung cancers. RING-SH2Grb² a chimeric protein of 215 amino acids containing the RING domain of Cbl that provides E3 ligase activity, and the SH2 domain of Grb2 that serves as an adaptor for EGFR. In this study, we demonstrated that RING-SH2Grb² could promote the ubiquitinylation and degradation of EGFR in a human non-small cell lung carcinoma cell line H1299. Moreover, we discovered that the RING-SH2Grb² chimera promoted the internalization of ligand-bound EGFR, inhibited the growth of H1299 cells, and significantly suppressed tumor growth in a xenograft mouse model. In summary, our results revealed a potential new cancer therapeutic approach for non-small cell lung cancer.


Assuntos
Receptores ErbB/fisiologia , Proteína Adaptadora GRB2/farmacologia , Proteínas Proto-Oncogênicas c-cbl/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/fisiologia , Animais , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Domínios de Homologia de src
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(3): 379-82, 2014 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-24943014

RESUMO

OBJECTIVE: To investigate the status of blood mineral content of children aged 3 to 12 years in Chinese cities and countryside and explore the possible related influencing factors. METHODS: The multistage stratified cluster random sampling was used to select one kindergarten and one primary school in seven cities (Beijing and Guangzhou and so on) and two towns randomly. Firstly, we selected one bottom class, middle class, top class in one kindergarten and one second grade and fifth grade in one primary school randomly. Then all of the healthful students of these classes were investigated and the blood mineral content of calcium, magnesium, lead, iron, copper, and zinc were detected. RESULTS: In the research, 1 842 students were investigated. The means of calcium, magnesium, lead, iron, copper, and zinc were in the standard range. The blood lead content of the boys was higher than that of the girls. The blood mineral content of different ages had statistical significance. The blood calcium and blood copper contents of the preschool children were higher than those of the school children. However, the school children had significantly higher blood lead, iron, and zinc contents in comparison with those of the preschool children. The incidences of iron deficiency and zinc deficiency were 35.5% and 39.6%, respectively. The incidence of iron deficiency and zinc deficiency of different ages had statistical significance, and with the age increasing, the incidence showed a decreasing trend. The incidences of iron deficiency and zinc deficiency of children whose age was more than or equal to 3 years and less than 4 years were up to 47.1% and 64.6%, respectively. The incidence of iron deficiency of the children in the countryside area was significantly higher than those in the first-tier cities. However, the incidence of zinc deficiency of the children in the countryside area was significantly lower than those in the first-tier cities and second-tier cities. CONCLUSION: The status of iron deficiency and zinc deficiency of children aged 3 to 12 years in Chinese cities and countryside were still serious. We should pay more attention to the nutrition interventional research on iron and zinc.


Assuntos
Minerais/sangue , Povo Asiático , Cálcio , Criança , Pré-Escolar , China , Cidades , Cobre , Feminino , Humanos , Incidência , Ferro , Chumbo , Magnésio , Masculino , Estudantes , Zinco
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(3): 383-8, 2014 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-24943015

RESUMO

OBJECTIVE: To evaluate the accuracy of parents' perception of whether their child is a picky eater and the specific food category the children avoideating according to the food frequency questionnaire. METHODS: This research selected 1 663 infants aged 4-36 months receiving non-diary complimentary food from maternal, infants, nutrition and growth study (MING Study) in 8 Chinese cities in which a combination of systematic cluster random sampling and purposive sampling was used. The general information, dietary status and picky eating status were collected through a self-designed questionnaire from the caregiver of the children. According to the parents' perception, the children were classified into picky/non-picky groups or avoid/non-avoid to a specific food category groups. Mann-Whitney U test was used to compare between the groups. RESULTS: The reported percentage of picky eaters increased from 7.37% in 4-6 months old infants to 36.20% in 25-36 months old infants. Most picky infants in 4-6 months and 7-12 months old infants avoided eating dairy food (25% and 24%); while most picky toddlers aged 13-24 months and 25-36 months avoided eating vegetables (26.92% and 47.46%). The infants aged 4-6 months and 7-12 months who were perceived as picky by their parents took more kinds of food (8 and 19.5 kinds) than those who were not (6 and 18 kinds), while the picky toddlers aged 13-24 months and 25-36 months took fewer kinds of food (28.5 and 34 kinds for picky eaters, 31 and 37 kinds for non-picky eaters). The parents of infants aged 4-6 months judged correctly in every category of food without any statistical significance; the parents of 7-12 months old infants judged correctly only in dairy food and eggs with statistical significance; those of 13-24 months old infants judged correctly in every food category except for vegetables with statistically significant difference in the category of eggs; those of 25-36 months old toddlers misjudged in dairy, beans and grains with no statistically significant difference in every category. CONCLUSION: Parents tend to misjudge their children's picky eating behavior before the first 12 months of the child, and tend to make a more accurate perception after the 12th month.


Assuntos
Comportamento Infantil , Preferências Alimentares , Pais , Pré-Escolar , Humanos , Lactente , Verduras
18.
J Nutr Health Aging ; 28(8): 100264, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772098

RESUMO

BACKGROUND: An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. DESIGN, SETTING, PARTICIPANTS: Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer's Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in ß-diversity were analyzed using permutational analysis of variance. RESULTS: A total of 605 participants aged 60-69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (ß, 2.92; 95% CI, 1.01-4.84). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio, 2.35; 95% CI, 1.28-4.30) and were less likely to experience subjective memory changes (adjusted odds ratio, 0.43; 95% CI, 0.25-0.74). In addition, ß-diversity was statistically significant for the cognitive performance status based on DSST (P = 0.031) and subjective memory changes (P = 0.023). CONCLUSIONS: Oral microbial composition was associated with executive function and subjective memory changes among older adults among older U.S. adults in a nationally representative population sample. Oral dysbiosis is a potential biomarker or therapeutic target for cognitive decline. Further work is needed to elucidate the mechanisms underpinning the association between the oral microbiome and cognitive function.

19.
Br J Nutr ; 110(5): 781-9, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23829939

RESUMO

High-protein diets are popular for weight management, but the health effects of such diets in diabetic persons are inconclusive. The aim of the present meta-analysis was to examine the effects of high-protein diets on body weight and metabolic risk factors in patients with type 2 diabetes. We searched the PubMed and Cochrane Library databases for relevant randomised trials up to August 2012. Either a fixed- or a random-effects model was used to combine the net changes in each outcome from baseline to the end of the intervention. Overall, nine trials including a total of 418 diabetic patients met our inclusion criteria. The study duration ranged from 4 to 24 weeks. The actual intake of dietary protein ranged from 25 to 32% of total energy in the intervention groups and from 15 to 20% in the control groups. Compared with the control diets, high-protein diets resulted in more weight loss (pooled mean difference: 22.08, 95% CI 23.25, 20.90 kg). High-protein diets significantly decreased glycated Hb A1C (HbA1C) levels by 0.52 (95% CI 20.90, 20.14) %, but did not affect the fasting blood glucose levels. There were no differences in lipid profiles. The pooled net changes in systolic and diastolic blood pressure were 23.13 (95% CI 26.58, 0.32)mmHg and 21.86 (95% CI 24.26, 0.56) mmHg, respectively. However, two studies reported a large influence on weight loss and HbA1C levels, respectively. In summary, high-protein diets (within 6 months) may have some beneficial effects on weight loss, HbA1C levels and blood pressure in patients with type 2 diabetes. However, further investigations are still required to draw a conclusion.


Assuntos
Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Alimentares/farmacologia , Lipídeos/sangue , Proteínas Alimentares/administração & dosagem , Humanos
20.
Zhonghua Fu Chan Ke Za Zhi ; 48(11): 833-7, 2013 Nov.
Artigo em Zh | MEDLINE | ID: mdl-24444560

RESUMO

OBJECTIVE: To compare the outcomes of in-vitro maturation (IVM) and in-vitro fertilization (IVF) after early follicular phase gonadotropin-releasing hormone agonist (GnRH-a) down-regulation in infertile patients with polycystic ovary syndrome (PCOS). METHODS: From July 2010 to December 2012, 72 infertile patients with PCOS undergoing assisted reproductive technology treatment in the Affiliated First Hospital of Wenzhou Medical University were enrolled in this study. The patients were divided into 2 groups, which were patients with early follicular phase down-regulation IVM (36 cases) at IVM group and early follicular phase down-regulation long protocol IVF (36 cases) at IVF group. The laboratory parameters and clinical outcomes were compared between two groups. RESULTS: (1) Lab parameters: a total of 442 oocytes were retrieved in group IVM, and 560 were in group IVF. The rate of mature oocytes of 83.8% (469/560) and high-quality embryos of 70.9% (212/299) at group IVF were significantly higher than that of group IVM[54.1% (239/442) and 50.7% (73/144), retrospectively, P < 0.01]. In group IVM, the average duration of gonadotropin (Gn) was (2.8 ± 1.5) days and the average dosage of Gn was (285 ± 169) U, which were significantly lower than (11.0 ± 1.0) days and (1499 ± 165) U in group IVF (P < 0.01). The mean number of oocytes retrieved 12.8 ± 2.5, fertilization rate of 64.8% (155/239), and implantation rate of 31% (23/74) in group IVM and 15.6 ± 3.1, 65.5% (307/469), 31% (23/74) in group IVF, which did not reach statistical difference (P > 0.05) . (2) Clinical outcomes: the clinical pregnancy rate (17/31, 55%) of IVF group was not significantly higher than that 44% (14/32) at IVM group (P > 0.05). The abortion rate was 1/17 at Group IVF and 1/14 in group IVM, which did not show statistical difference. Women at IVM group has no ovarian hyper-stimulation syndrome (OHSS) cycle, group IVF has 31% (11/36) cycles presented moderate and severe OHSS. CONCLUSIONS: Infertile patients with PCOS undergoing IVM and IVF treatment after early follicular phase GnRH-a down-regulation can get satisfactory laboratory and clinical outcome. In addition to short treatment cycle, IVM can also avoid the occurrence of OHSS completely, but it has a rising trend in the abortion rate. IVF has a high incidence of OHSS, meanwhile, it increases the dosage of gonadotropins.


Assuntos
Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Técnicas de Maturação in Vitro de Oócitos/métodos , Infertilidade Feminina/terapia , Oócitos/crescimento & desenvolvimento , Síndrome do Ovário Policístico/complicações , Adulto , Células Cultivadas , Regulação para Baixo , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/etiologia , Oócitos/efeitos dos fármacos , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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