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1.
Plant Cell ; 34(10): 4066-4087, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35880836

RESUMO

Most plant species can form symbioses with arbuscular mycorrhizal fungi (AMFs), which may enhance the host plant's acquisition of soil nutrients. In contrast to phosphorus nutrition, the molecular mechanism of mycorrhizal nitrogen (N) uptake remains largely unknown, and its physiological relevance is unclear. Here, we identified a gene encoding an AMF-inducible ammonium transporter, ZmAMT3;1, in maize (Zea mays) roots. ZmAMT3;1 was specifically expressed in arbuscule-containing cortical cells and the encoded protein was localized at the peri-arbuscular membrane. Functional analysis in yeast and Xenopus oocytes indicated that ZmAMT3;1 mediated high-affinity ammonium transport, with the substrate NH4+ being accessed, but likely translocating uncharged NH3. Phosphorylation of ZmAMT3;1 at the C-terminus suppressed transport activity. Using ZmAMT3;1-RNAi transgenic maize lines grown in compartmented pot experiments, we demonstrated that substantial quantities of N were transferred from AMF to plants, and 68%-74% of this capacity was conferred by ZmAMT3;1. Under field conditions, the ZmAMT3;1-dependent mycorrhizal N pathway contributed >30% of postsilking N uptake. Furthermore, AMFs downregulated ZmAMT1;1a and ZmAMT1;3 protein abundance and transport activities expressed in the root epidermis, suggesting a trade-off between mycorrhizal and direct root N-uptake pathways. Taken together, our results provide a comprehensive understanding of mycorrhiza-dependent N uptake in maize and present a promising approach to improve N-acquisition efficiency via plant-microbe interactions.


Assuntos
Compostos de Amônio , Micorrizas , Compostos de Amônio/metabolismo , Regulação da Expressão Gênica de Plantas , Micorrizas/fisiologia , Nitrogênio/metabolismo , Fósforo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Solo , Zea mays/metabolismo
2.
Anal Chem ; 96(21): 8365-8372, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38717986

RESUMO

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/imunologia , Técnicas Biossensoriais/métodos , Humanos , Imunoensaio/métodos , Ouro/química , Limite de Detecção
3.
Small ; 20(44): e2404347, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38958084

RESUMO

Solar-driven interfacial evaporation is an efficient method for purifying contaminated or saline water. Nonetheless, the suboptimal design of the structure and composition still necessitates a compromise between evaporation rate and service life. Therefore, achieving efficient production of clean water remains a key challenge. Here, a biomimetic dictyophora hydrogel based on loofah/carbonized sucrose@ZIF-8/polyvinyl alcohol is demonstrated, which can serve as an independent solar evaporator for clean water recovery. This special structural design achieves effective thermal positioning and minimal heat loss, while reducing the actual enthalpy of water evaporation. The evaporator achieves a pure water evaporation rate of 3.88 kg m-2 h-1 and a solar-vapor conversion efficiency of 97.16% under 1 sun irradiation. In comparison, the wastewater evaporation rate of the evaporator with ZIF-8 remains at 3.85 kg m-2 h-1 for 30 days, which is 16.3% higher than the light irradiation without ZIF-8. Equally important, the evaporator also showcases the capability to cleanse water from diverse sources of contaminants, including those with small molecules, oil, heavy metal ions, and bacteria, greatly improving the lifespan of the evaporator.

4.
Neuroendocrinology ; : 1-21, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39471791

RESUMO

INTRODUCTION: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method. RESULTS: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM.

5.
Wound Repair Regen ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925565

RESUMO

To evaluate the clinical evidence of platelet-rich plasma (PRP) in the treatment of venous ulcers (VUs). Electronic searches were conducted through the Cochrane Library, Web of Science, Embase and PubMed. AMSTAR-2 was used to assess the methodological quality. The quality of evidence was assessed using the GRADE system. According to AMSTAR-2, the methodological quality of the included reviews was generally inadequate owing to the limitations of entries 2, 4 and 7. Due to bias risk and imprecision, the evidence quality of the outcome measures was inadequate. In conclusion, PRP may have a therapeutic effect on VUs. However, this conclusion must be treated with caution due to methodological flaws of the included systematic reviews and meta-analyses.

6.
Exp Mol Pathol ; 136: 104889, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316203

RESUMO

Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.


Assuntos
Prurido , Pele , Humanos , Prurido/genética , Prurido/metabolismo , Queratinócitos , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais
7.
J Nat Prod ; 87(4): 884-892, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408342

RESUMO

The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC50: 8.8 vs 5.9 µM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 µM).


Assuntos
Sesquiterpenos , Humanos , Estereoisomerismo , Estrutura Molecular , Células Hep G2 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/síntese química
8.
Dev Psychopathol ; : 1-9, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39310941

RESUMO

One species-general life history (LH) principle posits that challenging childhood environments are coupled with a fast or faster LH strategy and associated behaviors, while secure and stable childhood environments foster behaviors conducive to a slow or slower LH strategy. This coupling between environments and LH strategies is based on the assumption that individuals' internal traits and states are independent of their external surroundings. In reality, individuals respond to external environmental conditions in alignment with their intrinsic vitality, encompassing both physical and mental states. The present study investigated attachment as an internal mental state, examining its role in mediating and moderating the association between external environmental adversity and fast LH strategies. A sample of 1169 adolescents (51% girls) from 9 countries was tracked over 10 years, starting from age 8. The results confirm both mediation and moderation and, for moderation, secure attachment nullified and insecure attachment maintained the environment-LH coupling. These findings suggest that attachment could act as an internal regulator, disrupting the contingent coupling between environmental adversity and a faster pace of life, consequently decelerating human LH.

9.
Psychol Res ; 88(2): 580-593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37707650

RESUMO

With the pace of life accelerating, multitasking has become the norm in daily life. According to research, multiple cognitive processes, including numerical reasoning, comprehension, and writing, are negatively affected by multitasking. However, only a few studies have investigated the relationship between multitasking and metacognition. In this study, the effect of multitasking on metacognition was examined using a prospective monitoring paradigm (prediction of subsequent recall performance). In Experiment 1, the participants simultaneously studied word pairs (primary task) and differentiated between different sound pitches (secondary task) and then predicted their performance in a subsequent memory test for the studied word pairs (prospective metacognitive monitoring). The accuracy of metacognitive evaluation with multitasking was then compared with that without multitasking. In Experiment 2, sounds and icons of real-life applications were used to improve the ecological validity of the experiment in the secondary task. The results indicated that multitasking impaired metacognition in both artificial and real-life simulated scenarios. In addition, the participants who engaged in more media multitasking in their daily lives exhibited poorer metacognitive monitoring abilities in single tasks.


Assuntos
Metacognição , Humanos , Estudos Prospectivos , Rememoração Mental , Resolução de Problemas , Compreensão
10.
J Sci Food Agric ; 104(5): 3100-3112, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38072653

RESUMO

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.


Assuntos
Curcumina , Nanopartículas , Curcumina/química , Antocianinas , Portadores de Fármacos/química , Polissacarídeos , Nanopartículas/química , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Soroalbumina Bovina/química
11.
Int J Psychol ; 59(4): 512-521, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38097526

RESUMO

To examine whether parents' cultural values are related to parenting practices and children's behavioural adjustment, mothers, fathers and children (N = 218) from two cities in China (Jinan and Shanghai) were interviewed when children were, on average, 10 years old. Mothers and fathers reported their endorsement of cultural values (individualism, collectivism, conformity), which were used to separately predict warmth and family obligation expectations reported by each parent, as well as children's report of parental psychological control, rule setting, knowledge solicitation and perceived family obligation expectations. Cross-informant (parents and child) composites of internalising and externalising behaviours were also obtained. The results showed that maternal individualism positively predicted parents' knowledge solicitation. Parental collectivism positively predicted their own warmth and family obligation expectations. Mothers' conformity positively predicted mothers' family obligation expectations, paternal warmth and children's perception of family obligation, whereas fathers' conformity only positively predicted fathers' family obligation expectations. These effects were largely consistent across regional subsamples, although mothers in Jinan were more collectivistic than mothers in Shanghai, and parents in Shanghai adopted less psychological control and more knowledge solicitation in parenting.


Assuntos
Comparação Transcultural , Poder Familiar , Valores Sociais , Humanos , China/etnologia , Poder Familiar/psicologia , Poder Familiar/etnologia , Feminino , Masculino , Criança , Valores Sociais/etnologia , Adulto , Controle Interno-Externo , Conformidade Social , Ajustamento Social , Relações Pais-Filho/etnologia
12.
Anal Chem ; 95(18): 7336-7343, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37129510

RESUMO

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.


Assuntos
Técnicas Biossensoriais , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Biomarcadores Tumorais/análise , Limite de Detecção , Imunoensaio , Ouro/química
13.
Trop Med Int Health ; 28(3): 203-214, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36617637

RESUMO

OBJECTIVES: To determine the prevalence of malnutrition status, analyse the association between malnutrition status and individual-level factors, and explore the spatial variation among children and adolescents living with HIV/AIDS in Tanzania. METHODS: The study is based on large-scale baseline routine data from the National AIDS Control Programme on people living with HIV from January 2016 to December 2021 in mainland Tanzania. 70,102 children and adolescents aged 5-19 years receiving active antiretroviral therapy were included in the analysis. Nutritional status of participants was assessed by anthropometric measurement. Pearson's Chi-square test was used to describe the association between individual-level factors with all malnutrition outcomes and spatial analysis was used to investigate spatial distribution of malnutrition. The excess risk of malnutrition for each region was calculated while Anselin Local Moran's I and Getis-Ord statistical tools were used to identify significant hot spots regions of malnutrition. RESULTS: The mean age of participants was 11.1 (SD 4.7) years, with 71.7% in the 5-14-year age group and 58.4% being girls. 39.2% were attending care and treatment clinics services at hospital level with public ownership. 53.4% started using ARV at age 5-14 years and 55.5% had already switched to second- or third-line ARV with 61.1% using ARV for less than 3 years. 51.2% were in WHO HIV clinical stage III or IV. The prevalence of malnutrition was 36.0% for stunting, 28.9% for underweight, 13.0% for wasting, and 48.0% for anthropometric failure. Individual-level factors which accounted for a higher proportion of malnutrition based on anthropometric failure were male sex (56.3%), age 5-14 years (50.0%), being unmarried (52.9%), being on second- or third-line ARV treatment (51.4%), ART initiation at age 5-14 years (55.7%), ARV for more than 3 years (49.4%), and stage IV of WHO HIV clinical status (57.8%). There were regional hot spots (p < 0.05): the prevalence rate and excess risk of malnutrition for stunting and anthropometric failure were highest in the southern highlands regions, for underweight in the central regions, and for wasting in the northern regions. CONCLUSIONS: Children and adolescents living with HIV/AIDS in Tanzania suffer from poor nutritional status. Malnutrition does not occur arbitrarily, and the regions identified as hot spots should be given priority for nutritional intervention. Effective nutritional interventions for children living with HIV/AIDS should incorporate multiple approaches by considering unique geographical factors.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Desnutrição , Feminino , Humanos , Masculino , Criança , Adolescente , Lactente , Pré-Escolar , Tanzânia/epidemiologia , Magreza/epidemiologia , Desnutrição/epidemiologia , Estado Nutricional , Prevalência , Transtornos do Crescimento/epidemiologia
14.
J Org Chem ; 88(23): 16511-16519, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37972539

RESUMO

The first synthesis of ustusal A as well as expeditious access to (-)-albrassitriol is described as featuring a singlet oxygen [4 + 2] cycloaddition, achieving the desired stereoselectivity for the 1,4-cis-hydroxyl groups. Transformation of (+)-sclareolide to III followed by a key Horner-Wadsworth-Emmons (HWE) reaction and stereospecific allylic oxidation facilitated the first synthesis of elegansin D. The biological evaluation of these natural products together with seven elegansin D analogues was performed, among which several elegansin D analogues exhibited potential anticancer activity against liver cancer HepG2 cells (IC50 = 11.99-25.58 µM) with low cytotoxicity on normal liver HL7702 cells (IC50 > 100 µM).


Assuntos
Estereoisomerismo , Oxirredução
15.
Acta Pharmacol Sin ; 44(8): 1676-1686, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36859596

RESUMO

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus, and oxidative stress and mitochondrial dysfunction play an important role in this process. It has been shown that aldose reductase (ALR2) catalyzes NADPH-dependent reduction of glucose to sorbitol, resulting in oxidative stress and mitochondrial dysfunction in diabetic patients. Astragalin (AG), a flavonoid extracted from Thesium chinense Turcz., shows an inhibitory activity on ALR2. In this study, we investigated the therapeutic effects of AG against renal injury in streptozocin (STZ)-induced diabetic mouse model. Diabetic mice were orally administered AG (5, 10 mg·kg-1·d-1) for 4 weeks. We showed that AG treatment greatly improved the proteinuria and ameliorated renal pathological damage without affecting the elevated blood glucose in diabetic mice. Furthermore, AG treatment significantly suppressed highly activated ALR2, and reduced oxidative stress in the kidney of diabetic mice and in high glucose and lipids-stimulated HK2 cells in vitro. We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 µM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control. We conclude that AG could be a promising drug candidate for the treatment of diabetic renal injury through activating AMPK.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Peróxido de Hidrogênio/farmacologia , Rim/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Glucose/metabolismo , Mitocôndrias , Lipídeos
16.
Acta Pharmacol Sin ; 44(10): 2004-2018, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37225844

RESUMO

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.


Assuntos
Fator 10 de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Animais , Camundongos , Doxorrubicina , Fator 10 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição
17.
Antonie Van Leeuwenhoek ; 116(6): 511-519, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37022511

RESUMO

A aerobic, gram-negative, rod-shaped and polar-flagellum bacterial strain, designated as FYR11-62T, was isolated from the estuary of the Fenhe River into the Yellow River in Shanxi Province, China. The isolate was able to grow at 4-37 °C (optimum, 25 °C), pH 5.5-9.5 (optimum, pH 7.5) and in the presence of 0-7.0% (w/v) NaCl (optimum, 1.0% NaCl). Phylogenetic analyses based on 16S rRNA genes and 1597 single-copy orthologous clusters indicated that strain FYR11-62T affiliated with the genus Shewanella and shared the highest 16S rRNA gene sequence similarity to Shewanella aestuarii SC18T (98.3%) and Shewanella gaetbuli TF-27T (97.3%), respectively. The major fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and iso-C15:0. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The main quinones were Q-7 and Q-8. The genomic DNA G + C content was 41.6%. Gene annotation showed that strain FYR11-62T possessed 30 antibiotic resistance genes, implying its multiple antidrug resistance. The average nucleotide identity and digital DNA-DNA hybridization values between strain FYR11-62T and its closely related species were all below the thresholds for species delineation. The phylogenetic position together with the results of the analysis of morphological, physiological and genomic features support the classification of strain FYR11-62T (= MCCC 1K07242T = KCTC 92244T) as a novel species of the genus Shewanella, for which the name Shewanella subflava sp. nov. is proposed.


Assuntos
Rios , Shewanella , Rios/microbiologia , Filogenia , Estuários , RNA Ribossômico 16S/genética , Cloreto de Sódio , Análise de Sequência de DNA , Ácidos Graxos/análise , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , DNA Bacteriano/química , Fosfolipídeos/análise
18.
Curr Microbiol ; 80(11): 343, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37725183

RESUMO

A Gram-negative, aerobic, motile by flagellum, and rod-shaped bacterium, designated ASW11-7T, was isolated from coastal surface seawater sample collected from the Yellow Sea, PR China. Strain ASW11-7T grew optimally at 37℃, 4.0% (w/v) NaCl and pH 7.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain ASW11-7T belongs to the genus Alteromonas and most closely related to Alteromonas ponticola MYP5T (99.6% similarity), followed by Alteromonas confluentis DSSK2-12T (98.2%), Alteromonas lipolytica JW12T (98.2%), and Alteromonas hispanica F-32T (98.0%). The draft genome of strain ASW11-7T had a length of 3,530,922 bp with a G + C content of 44.9%, predicting 3108 coding sequences, 5 rRNA, 4 ncRNAs, 49 tRNAs genes, and 18 pseudogenes. The average nucleotide identity and digital DNA-DNA hybridization values between genomic sequences of strain ASW11-7T and closely related species of Alteromonas were in ranges of 66.9-77.8% and 18.3-27.5%, respectively. The major fatty acids of strain ASW11-7T were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), and summed feature 8 (C18:1ω7c/C18:1ω6c). The predominant respiratory quinone was Q-8 and the major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Based on the phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain ASW11-7T is considered to represent a novel Alteromonas species, for which the name Alteromonas aquimaris sp. nov. is proposed. The type strain is ASW11-7T (= KCTC 92853T = MCCC 1K07240T).


Assuntos
Alteromonas , Alteromonas/genética , Filogenia , RNA Ribossômico 16S/genética , China , DNA
19.
BMC Public Health ; 23(1): 1819, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726699

RESUMO

BACKGROUND: Schools play an organizational role in managing myopia-related behavioral habits among students. We evaluated the effects of school myopia management measures on myopia onset and progression in a school-based prospective 1-year observational study. METHODS: In total, 8319 children from 26 elementary schools were included. Online questionnaire completed by a parent, in which school myopia management experience including outdoor activities in recess or physical education class, teachers' supervision, and teaching facilities. Variables were defined as implemented well or poorly, according to the Comprehensive Plan to Prevent Myopia among Children and Teenagers. Children underwent ophthalmic examinations, and the incidence and progression of myopia from 2019 to 2020 were estimated. Multilevel logistic regression models were constructed to analyze the association between school management measures and myopia development in 8,9 years and 10,11 years students. RESULTS: From 2019 to 2020, the incidence of myopia among primary school students was 36.49%; the mean difference of spherical equivalent in myopic children was - 0.29 ± 1.22 diopters. The risk of incident myopia was reduced by 20% in 8,9 years participants with well-implemented class recess compared with those with poorly implemented class recess (adjusted odds ratio [aOR]: 0.80, p = 0.032). PE outdoor time was significantly associated with myopia incidence in 10,11 years students (aOR: 0.76, p = 0.043). Compared with poorly implemented reading and writing posture, desk and chair height, 10,11 participants with well-implemented desk and chair height were less likely to have rapid myopic progression (p = 0.029, p = 0.022). CONCLUSION: In Shanghai, children's myopia is associated with better implementation of school myopia management measures. The present findings suggest that outdoor activities during class recess or PE class, providing suitable desks and chairs, and adequate instruction in reading and writing postures might protect against pathological eye growth. An age-specific myopia prevention and control programs in school is of primary importance.


Assuntos
População do Leste Asiático , Miopia , Criança , Humanos , China/epidemiologia , Miopia/epidemiologia , Miopia/prevenção & controle , Estudos Prospectivos , Estudantes
20.
Proc Natl Acad Sci U S A ; 117(40): 24974-24985, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958637

RESUMO

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B2 synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled stable MR1 antigen analog, a conformation-specific MR1 mAb, proteomic analysis, and a genome-wide CRISPR/Cas9 library screen. We show that the endoplasmic reticulum (ER) contains a pool of two unliganded MR1 conformers stabilized via interactions with chaperones tapasin and tapasin-related protein. This pool is the primary source of MR1 molecules for the presentation of exogenous metabolite antigens to MAIT cells. Deletion of these chaperones reduces the ER-resident MR1 pool and hampers antigen presentation and MAIT cell activation. The MR1 antigen-presentation pathway thus co-opts ER chaperones to fulfill its unique ability to present exogenous metabolite antigens captured within the ER.


Assuntos
Retículo Endoplasmático/genética , Antígenos de Histocompatibilidade Classe I/genética , Metaboloma/genética , Antígenos de Histocompatibilidade Menor/genética , Proteômica , Apresentação de Antígeno/genética , Antígenos/genética , Antígenos/imunologia , Sistemas CRISPR-Cas/genética , Humanos , Ligantes , Ativação Linfocitária/genética , Proteínas de Membrana Transportadoras/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Riboflavina/genética
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