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1.
Thromb Haemost ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38959956

RESUMO

BACKGROUND: Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). However, currently there are no tools specifically designed for predicting the occurrence of SIC in septic patients earlier. This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients. METHODS: Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to externally validate the nomogram. Univariate logistic regression analysis of the development cohort was performed firstly, and then multivariate logistic regression analysis was performed using backward stepwise method to determine the best-fitting model and obtain the nomogram from it. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram. RESULTS: A total of 548 and 245 patients, 55.1 and 49.4% with SIC occurrence, were included in the development and validation cohorts, respectively. Predictors contained in the prediction nomogram included shock, platelets, and international normalized ratio (INR). Patients with shock (odds ratio [OR]: 4.499; 95% confidence interval [CI]: 2.730-7.414; p < 0.001), higher INR (OR: 349.384; 95% CI: 62.337-1958.221; p < 0.001), and lower platelet (OR: 0.985; 95% CI: 0.982-0.988; p < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.879 (95% CI: 0.850-0.908) and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872 (95% CI: 0.826-0.917) and good calibration. The decision curve analysis of the nomogram provided better net benefit than the alternate options (intervention or no intervention). CONCLUSION: By incorporating shock, platelets, and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients. However, external validation is still required for further generalizability improvement of this nomogram.

2.
Molecules ; 29(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38998922

RESUMO

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal-organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10-4~10-5 µL/mL, with a low detection limit of 8.12 × 10-4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.

3.
J Immunol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949555

RESUMO

Aberrant activity of NLRP3 has been shown associations with severe diseases. Palmitoylation is a kind of protein post-translational modification, which has been shown to regulate cancer development and the innate immune system. Here, we showed that NLRP3 is palmitoylated at Cys419 and that palmitoyltransferase ZDHHC17 is the predominant enzyme that mediates NLRP3 palmitoylation and promotes NLRP3 activation by interacting with NLRP3 and facilitating NIMA-related kinase 7 (NEK7)-NLRP3 interactions. Blockade of NLRP3 palmitoylation by a palmitoylation inhibitor, 2-bromopalmitate, effectively inhibited NLRP3 activation in vitro. Also, in a dextran sulfate sodium-induced colitis model in mice, 2-bromopalmitate application could attenuate weight loss, improve the survival rate, and rescue pathological changes in the colon of mice. Overall, our study reveals that palmitoylation of NLPR3 modulates inflammasome activation and inflammatory bowel disease development. We propose that drugs targeting NLRP3 palmitoylation could be promising candidates in the treatment of NLRP3-mediated inflammatory diseases.

4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 527-531, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38952092

RESUMO

Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE-/- mouse model of atherosclerosis. Methods Aortic specimens were carefully excised from the ApoE-/- mouse model. Following immunostaining with specific antibodies against smooth muscle actin (SMA) and lymphatic vessel endothelial receptor 1 (LYVE1), the aortas, including the aortic root, were subjected to a 30-minute treatment with 5 g/L Sudan Black B solution. This step was instrumental in minimizing the autofluorescent background of the tissue. Thereafter, the aortas were processed through a clearing protocol and imaged within a purpose-built chamber under a fluorescence microscope. Results The pretreatment with 5 g/L Sudan Black B effectively suppressed the autofluorescent signals emanating from the vascular structures, thereby enhancing the contrast and clarity of the specific fluorescence signals associated with the lymphatic vessels. This enhancement in signal quality did not compromise the integrity or specificity of the immunofluorescent markers. Conclusion A facile, highly specific, and effective approach for the visualization of lymphatic vessels in whole-mount aortic preparations from ApoE-/- mice is established.


Assuntos
Aorta , Apolipoproteínas E , Imunofluorescência , Vasos Linfáticos , Animais , Vasos Linfáticos/metabolismo , Vasos Linfáticos/diagnóstico por imagem , Camundongos , Aorta/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Imunofluorescência/métodos , Túnica Adventícia/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coloração e Rotulagem/métodos , Microscopia de Fluorescência/métodos
5.
Eur J Med Chem ; 276: 116639, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38964259

RESUMO

Since influenza virus RNA polymerase subunit PAN is a dinuclear Mn2+ dependent endonuclease, metal-binding pharmacophores (MBPs) with Mn2+ coordination has been elucidated as a promising strategy to develop PAN inhibitors for influenza treatment. However, few attentions have been paid to the relationship between the optimal arrangement of the donor atoms in MBPs and anti-influenza A virus (IAV) efficacy. Given that, the privileged hydroxypyridinones fusing a seven-membered lactam ring with diverse side chains, chiral centers or cyclic systems were designed and synthesized. A structure-activity relationship study resulted in a hit compound 16l (IC50 = 2.868 ± 0.063 µM against IAV polymerase), the seven-membered lactam ring of which was fused a pyrrolidine ring. Further optimization of the hydrophobic binding groups on 16l afforded a lead compound (R, S)-16s, which exhibited a 64-fold more potent inhibitory activity (IC50 = 0.045 ± 0.002 µM) toward IAV polymerase. Moreover, (R, S)-16s demonstrated a potent anti-IAV efficacy (EC50 = 0.134 ± 0.093 µM) and weak cytotoxicity (CC50 = 15.35 µM), indicating the high selectivity of (R, S)-16s. Although the lead compound (R, S)-16s exhibited a little weaker activity than baloxavir, these findings illustrated the utility of a metal coordination-based strategy in generating novel MBPs with potent anti-influenza activity.

6.
Molecules ; 29(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38893327

RESUMO

Magnesium-based hydrogen storage materials have garnered significant attention due to their high hydrogen storage capacity, abundance, and low cost. However, the slow kinetics and high desorption temperature of magnesium hydride hinder its practical application. Various preparation methods have been developed to improve the hydrogen storage properties of magnesium-based materials. This review comprehensively summarizes the recent advances in the preparation methods of magnesium-based hydrogen storage materials, including mechanical ball milling, methanol-wrapped chemical vapor deposition, plasma-assisted ball milling, organic ligand-assisted synthesis, and other emerging methods. The principles, processes, key parameters, and modification strategies of each method are discussed in detail, along with representative research cases. Furthermore, the advantages and disadvantages of different preparation methods are compared and evaluated, and their influence on hydrogen storage properties is analyzed. The practical application potential of these methods is also assessed, considering factors such as hydrogen storage performance, scalability, and cost-effectiveness. Finally, the existing challenges and future research directions in this field are outlined, emphasizing the need for further development of high-performance and cost-effective magnesium-based hydrogen storage materials for clean energy applications. This review provides valuable insights and references for researchers working on the development of advanced magnesium-based hydrogen storage technologies.

7.
Molecules ; 29(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893401

RESUMO

Magnesium-based hydrogen storage alloys have attracted significant attention as promising materials for solid-state hydrogen storage due to their high hydrogen storage capacity, abundant reserves, low cost, and reversibility. However, the widespread application of these alloys is hindered by several challenges, including slow hydrogen absorption/desorption kinetics, high thermodynamic stability of magnesium hydride, and limited cycle life. This comprehensive review provides an in-depth overview of the recent advances in magnesium-based hydrogen storage alloys, covering their fundamental properties, synthesis methods, modification strategies, hydrogen storage performance, and potential applications. The review discusses the thermodynamic and kinetic properties of magnesium-based alloys, as well as the effects of alloying, nanostructuring, and surface modification on their hydrogen storage performance. The hydrogen absorption/desorption properties of different magnesium-based alloy systems are compared, and the influence of various modification strategies on these properties is examined. The review also explores the potential applications of magnesium-based hydrogen storage alloys, including mobile and stationary hydrogen storage, rechargeable batteries, and thermal energy storage. Finally, the current challenges and future research directions in this field are discussed, highlighting the need for fundamental understanding of hydrogen storage mechanisms, development of novel alloy compositions, optimization of modification strategies, integration of magnesium-based alloys into hydrogen storage systems, and collaboration between academia and industry.

8.
Molecules ; 29(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38893436

RESUMO

Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y. Li belongs to the genus Bupleurum and is distinguished for its high level of saikosaponins and volatile oils; nonetheless, prevailing evidence remains inconclusive regarding its viability as an alternative resource of other official species. This study aims to systematically compare the volatile oil components of both dried and fresh roots of B. marginatum var. stenophyllum and the four legally available Bupleurum species across their chemical, molecular, bionics, and anatomical structures. A total of 962 compounds were determined via GC-MS from the dried roots; B. marginatum var. stenophyllum showed the greatest differences from other species in terms of hydrocarbons, esters, and ketones, which was consistent with the results of fresh roots and the e-nose analysis. A large number of DEGs were identified from the key enzyme family of the monoterpene synthesis pathway in B. marginatum var. stenophyllum via transcriptome analysis. The microscopic observation results, using different staining methods, further showed the distinctive high proportion of phloem in B. marginatum var. stenophyllum, the structure which produces volatile oils. Together, these pieces of evidence hold substantial significance in guiding the judicious development and utilization of Bupleurum genus resources.


Assuntos
Bupleurum , Óleos Voláteis , Raízes de Plantas , Óleos Voláteis/química , Bupleurum/química , Raízes de Plantas/química , Cromatografia Gasosa-Espectrometria de Massas , Plantas Medicinais/química
9.
Materials (Basel) ; 17(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38893774

RESUMO

Mg-based materials have been widely studied as potential hydrogen storage media due to their high theoretical hydrogen capacity, low cost, and abundant reserves. However, the sluggish hydrogen absorption/desorption kinetics and high thermodynamic stability of Mg-based hydrides have hindered their practical application. Ball milling has emerged as a versatile and effective technique to synthesize and modify nanostructured Mg-based hydrides with enhanced hydrogen storage properties. This review provides a comprehensive summary of the state-of-the-art progress in the ball milling of Mg-based hydrogen storage materials. The synthesis mechanisms, microstructural evolution, and hydrogen storage properties of nanocrystalline and amorphous Mg-based hydrides prepared via ball milling are systematically reviewed. The effects of various catalytic additives, including transition metals, metal oxides, carbon materials, and metal halides, on the kinetics and thermodynamics of Mg-based hydrides are discussed in detail. Furthermore, the strategies for synthesizing nanocomposite Mg-based hydrides via ball milling with other hydrides, MOFs, and carbon scaffolds are highlighted, with an emphasis on the importance of nanoconfinement and interfacial effects. Finally, the challenges and future perspectives of ball-milled Mg-based hydrides for practical on-board hydrogen storage applications are outlined. This review aims to provide valuable insights and guidance for the development of advanced Mg-based hydrogen storage materials with superior performance.

10.
Huan Jing Ke Xue ; 45(6): 3688-3699, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897788

RESUMO

The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.


Assuntos
Biodegradação Ambiental , Microplásticos , Hidrocarbonetos Policíclicos Aromáticos , Polietileno , Microbiologia do Solo , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Solo/química , Bactérias/classificação , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Bactérias/efeitos dos fármacos , Oxigênio/metabolismo
11.
Acta Pharmacol Sin ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914676

RESUMO

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

12.
Nat Commun ; 15(1): 5312, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906856

RESUMO

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.


Assuntos
Exposição Materna , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro , Humanos , Feminino , Gravidez , China/epidemiologia , Exposição Materna/efeitos adversos , Adulto , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Resultado da Gravidez/epidemiologia , Didrogesterona/efeitos adversos , Progesterona , Coorte de Nascimento , Recém-Nascido , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/induzido quimicamente , Natimorto/epidemiologia , Recém-Nascido de Baixo Peso , Estudos Longitudinais , Incidência , Adulto Jovem
13.
Angew Chem Int Ed Engl ; : e202404598, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38945836

RESUMO

Acetic acid (AA), a vital compound in chemical production and materials manufacturing, is conventionally synthesized by starting with coal or methane through multiple steps including high-temperature transformations. Here we present a new synthesis of AA from ethane through photocatalytic selective oxidation of ethane by H2O2 at 0-25°C. The catalyst designed for this process comprises g-C3N4 with anchored Pd1 single-atom sites. In-situ studies and computational simulation suggest the immobilized Pd1 atom becomes positively charged under photocatalytic condition. Under photoirradiation, the holes on the Pd1 single-atom of OH-Pd1Å/g-C3N4 serves as a catalytic site for activating a C-H instead of C-C of C2H6 with a low activation barrier of 0.14 eV, through a concerted mechanism. Remarkably, the selectivity for synthesizing AA reaches 98.7%, achieved under atmospheric pressure of ethane at 0°C. By integrating photocatalysis with thermal catalysis, we introduce a highly selective, environmentally friendly, energy-efficient synthetic route for AA, starting from ethane, presenting a promising alternative for AA synthesis. This integration of photocatalysis in low-temperature oxidation demonstrates a new route of selective oxidation of light alkanes.

14.
Biosens Bioelectron ; 262: 116530, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38943854

RESUMO

The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.

15.
Psych J ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922771

RESUMO

Although the world has entered the post-pandemic period, the mental health and life satisfaction of college students still need to be addressed. However, previous literature has primarily focused on negative variables and has paid little attention to positive variables, such as self-compassion and the capacity to be alone. Therefore, this longitudinal study aims to investigate the relationships between the capacity to be alone, self-compassion, life satisfaction, depression, and anxiety among college students. This study analyzed data from 1460 Chinese college students who completed an online survey at two time-points one year apart. We employed cross-lagged analysis and constructed longitudinal mediation models to explore the relationships between five variables (i.e., capacity to be alone, self-compassion, life satisfaction, depression, and anxiety). Our findings indicate that depression and life satisfaction could negatively predict each other over time. Self-compassion in wave 1 could negatively predict depression and anxiety in wave 2. Higher life satisfaction in wave 1 was associated with a lower capacity to be alone in wave 2. We also found reciprocal positive predictive relationships between depression and anxiety, and life satisfaction and self-compassion. Life satisfaction mediated the relationship between self-compassion and psychopathological variables (i.e., depression and anxiety). Additionally, self-compassion mediated the association between life satisfaction and psychopathological variables and the association between capacity to be alone and psychopathological variables. Our study highlights the significance of early identification and intervention in depression and anxiety. We also discovered the possible self-soothing function of self-compassion as well as the importance of fostering positive personal characteristics.

16.
Nanomaterials (Basel) ; 14(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38921912

RESUMO

Hydrogen energy, known for its high energy density, environmental friendliness, and renewability, stands out as a promising alternative to fossil fuels. However, its broader application is limited by the challenge of efficient and safe storage. In this context, solid-state hydrogen storage using nanomaterials has emerged as a viable solution to the drawbacks of traditional storage methods. This comprehensive review delves into the recent advancements in nanomaterials for solid-state hydrogen storage, elucidating the fundamental principles and mechanisms, highlighting significant material systems, and exploring the strategies of surface and interface engineering alongside catalytic enhancement. We also address the primary challenges and provide future perspectives on the development of nanomaterial-based hydrogen storage technologies. Key discussions include the role of nanomaterial size effects, surface modifications, nanocomposites, and nanocatalysts in optimizing storage performance.

17.
Int Immunopharmacol ; 137: 112483, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38880023

RESUMO

Renal fibrosis is a representative pathological feature of various chronic kidney diseases, and efficient treatment is needed. Interstitial myofibroblasts are a key driver of kidney fibrosis, which is dependent on the binding of TGF-ß1 to type I TGF-ß receptor (TßRI) and TGF-ß1-related signaling pathways. Therefore, attenuating TGF-ß1 activity by competing with TGF-ß1 in myofibroblasts is an ideal strategy for treating kidney fibrosis. Recently, a novel TßRI-mimicking peptide RIPΔ demonstrated a high affinity for TGF-ß1. Thus, it could be speculated that RIPΔ may be used for anti-fibrosis therapy. Platelet-derived growth factor ß receptor (PDGFßR) is highly expressed in fibrotic kidney. In this study, we found that target peptide Z-RIPΔ, which is RIPΔ modified with PDGFßR-specific affibody ZPDGFßR, was specifically and highly taken up by TGF-ß1-activated NIH3T3 fibroblasts. Moreover, Z-RIPΔ effectively inhibited the myofibroblast proliferation, migration and fibrosis response in vitro. In vivo and ex vivo experiments showed that Z-RIPΔ specifically targeted fibrotic kidney, improved the damaged renal function, and ameliorated kidney histopathology and renal fibrosis in UUO mice. Mechanistic studies showed that Z-RIPΔ hold the stronger inhibition of the TGF-ß1/Smad and TGF-ß1/p38 pathways than unmodified RIPΔ in vitro and in vivo. Furthermore, systemic administration of Z-RIPΔ to UUO mice led to minimal toxicity to major organs. Taken together, RIPΔ modified with ZPDGFßR increased its therapeutic efficacy and reduced its systemic toxicity, making it a potential candidate for targeted therapy for kidney fibrosis.


Assuntos
Fibrose , Rim , Camundongos Endogâmicos C57BL , Proteínas Smad , Fator de Crescimento Transformador beta1 , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Fibrose/tratamento farmacológico , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Células NIH 3T3 , Masculino , Proteínas Smad/metabolismo , Transdução de Sinais/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Humanos , Modelos Animais de Doenças , Proliferação de Células/efeitos dos fármacos
18.
Chem Biol Interact ; 398: 111090, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825057

RESUMO

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play pivotal roles in the pathology of cerebral ischemia. In this study, we investigated whether phelligridimer A (PA), an active compound isolated from the medicinal and edible fungus Phellinus igniarius, ameliorates ischemic cerebral injury by restoring mitochondrial function and restricting ER stress. An in vitro cellular model of ischemic stroke-induced neuronal damage was established by exposing HT-22 neuronal cells to oxygen-glucose deprivation/reoxygenation (OGD/R). An in vivo animal model was established in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The results showed that PA (1-10 µM) dose-dependently increased HT-22 cell viability, reduced OGD/R-induced lactate dehydrogenase release, and reversed OGD/R-induced apoptosis. PA reduced OGD/R-induced accumulation of reactive oxygen species, restored mitochondrial membrane potential, and increased ATP levels. Additionally, PA reduced the expression of the 78-kDa glucose-regulated protein (GRP78) and the phosphorylation of inositol-requiring enzyme-1α (p-IRE1α) and eukaryotic translation-initiation factor 2α (p-eIF2α). PA also inhibited the activation of the mitogen-activated protein kinase (MAPK) pathway in the OGD/R model. Moreover, treatment with PA restored the expression of mitofusin 2 (Mfn-2), a protein linking mitochondria and ER. The silencing of Mfn-2 abolished the protective effects of PA. The results from the animal study showed that PA (3-10 mg/kg) significantly reduced the volume of cerebral infarction and neurological deficits, which were accompanied by an increased level of Mfn-2, and decreased activation of the ER stress in the penumbra of the ipsilateral side after MCAO/R in rats. Taken together, these results indicate that PA counteracts cerebral ischemia-induced injury by restoring mitochondrial function and reducing ER stress. Therefore, PA might be a novel protective agent to prevent ischemia stroke-induced neuronal injury.


Assuntos
Isquemia Encefálica , Estresse do Retículo Endoplasmático , GTP Fosfo-Hidrolases , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , GTP Fosfo-Hidrolases/metabolismo , Ratos , Masculino , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Chaperona BiP do Retículo Endoplasmático/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Glucose/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas de Choque Térmico/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fator de Iniciação 2 em Eucariotos/metabolismo
19.
Food Chem ; 456: 139968, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38861865

RESUMO

Galactooligosaccharides (GOS) are important prebiotics with function closely related to their structure. However, a comprehensive overview of the structure-function relationship is still limited due to the challenge in characterizing multiple isomers in GOS. This study presents a strategy of combining both hydrophilic interaction liquid chromatography (HILIC) retention time and tandem mass spectrometry (MS/MS) fragmentation pattern to distinguish α/ß-linkages and linkage positions of disaccharide isomers in GOS through HILIC-MS/MS analysis. The results indicated that the ratio of m/z 203.0524 to m/z 365.1054 could distinguish α/ß-linkages, while the ratios of m/z 347.0947 to m/z 365.1054, m/z 245.0642 to m/z 365.1054 and HILIC retention time could distinguish (1 â†’ 2), (1 â†’ 3), (1 â†’ 4) and (1 â†’ 6) linkages. The above rules enabled effective characterization of disaccharides in GOS-containing food samples, including milk powder, rice flour, drink, yogurt. This method can be used in the quality control of GOS and future research on the structure-specific health effects of GOS.

20.
ACS Omega ; 9(23): 24453-24463, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38882099

RESUMO

Biomass waste and wastewater are important wastes in the process of industrialization, which need to be effectively treated and utilized. In this work, an innovative method of collaborative treatment of biomass waste and phenol-containing wastewater is proposed. Biomass waste was used to produce activated carbon (AC), and then AC was used for phenol removal in wastewater treatment. Two kinds of typical biomass waste material, namely, coconut shell and lignin, were used. Physical activation (steam activation) and chemical activation methods were compared. Results show that steam activation is an effective method for coconut shell AC production. The largest Brunauer-Emmett-Teller (BET) surface area was 1065 m2/g at 800 °C. Chemical activation could produce AC samples with higher BET specific surface area. The lignin AC with K2CO3 activation has the largest BET surface of 1723.8 m2/g at 800 °C. FTIR results indicated that K2CO3 activation could greatly enhance the formation of surface oxygen-containing functional groups. Both coconut shell AC and lignin AC samples show excellent performance for phenol removal. The highest phenol removal efficiency for coconut shell AC and lignin AC are 96.87% and 98.22%, respectively. Adsorption kinetic analysis show that the pseudo-first-order kinetic model is able to describe the adsorption characteristics of phenol in wastewater treatment. Recycling properties show that regeneration of lignin AC could maintain high adsorption performance for phenol.

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