Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 201
Filtrar
1.
Front Psychol ; 15: 1288711, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770260

RESUMO

Earth Hour, a global mass effort coordinated to show concern for green urban construction and sustainable development, was first organized by the World Wildlife Fund in Australia in 2007 with a growing trend of participation worldwide. However, analysis of participation in Earth Hour based on a large population are sparse, with only a few studies reporting details in positive results without a clear pattern that explains the potential low participation. This study focuses on the non-participants and analyzed the reasons for low participation in Earth Hour using a questionnaire with 401 college students based on the socio-ecological model. Two aspects are explored: (1) social-demographic features; (2) psychosocial traits (environmental awareness, acceptance for law, social support from family and friends and knowledge about the event). Barriers toward participation are included as mediators to explain how these basic features change students' decision on joining large-scale environmental campaign. A participation analysis method using binary logistic regression and one-way MANOVA is applied in data analysis. This study highlights that the irrelevance between students' belief and practice on environmental protection should not be overlooked, and that college students are inclined to join in groups in relevant activities-conversely, herd effect could greatly reduce their willingness to participation. The findings of this study have wider implications for school educators, practitioners and organizations involved in pro-environmental career. This paper highlights that, from an international perspective, the essence of collective action with a similar nature to Earth Hour and contributes to a global dialogue on fostering sustainable behaviors.

2.
Int J Biol Macromol ; 269(Pt 2): 131967, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692528

RESUMO

The development of food-grade high internal phase emulsions (HIPEs) for 3D printing and the replacement of animal fats have attracted considerable attention. In this study, in order to improve the rheological properties and stability of pea protein to prepare HIPE, pea protein/carboxymethyl cellulose (pH-PP/CMC) was prepared and subjected to pH cycle treatment to produce HIPEs. The results showed that pH cycle treatment and CMC significantly reduced the droplet size of HIPEs (from 143.33 to 12.10 µm). At higher CMC concentrations, the interfacial tension of the PP solution decreased from 12.84 to 11.71 mN/m without pH cycle treatment and to 10.79 mN/m with pH cycle treatment. The HIPEs with higher CMC concentrations subjected to pH cycle treatment showed shear thinning behavior and higher viscoelasticity and recovered their solid-like properties after being subjected to 50 % strain, indicating that they could be used for 3D printing. The 3D printing results showed that the pH-PP/CMC HIPE with 0.3 % CMC had the finest structure. Our work provides new insights into developing food-grade HIPEs and facilitating their use in 3D printing inks as nutrient delivery systems and animal fat substitutes.

3.
Adv Sci (Weinh) ; : e2309907, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696589

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

4.
Mol Psychiatry ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698268

RESUMO

Both clinical and animal studies showed that the impaired functions of the orbitofrontal cortex (OFC) underlie the compulsive drug-seeking behavior of drug addiction. However, the functional changes of the microcircuit in the OFC and the underlying molecular mechanisms in drug addiction remain elusive, and little is known for whether microcircuits in the OFC contributed to drug addiction-related behaviors. Utilizing the cocaine-induced conditioned-place preference model, we found that the malfunction of the microcircuit led to disinhibition in the OFC after cocaine withdrawal. We further showed that enhanced Somatostatin-Parvalbumin (SST-PV) inhibitory synapse strength changed microcircuit function, and SST and PV inhibitory neurons showed opposite contributions to the drug addiction-related behavior of mice. Brevican of the perineuronal nets of PV neurons regulated SST-PV synapse strength, and the knockdown of Brevican alleviated cocaine preference. These results reveal a novel molecular mechanism of the regulation of microcircuit function and a novel circuit mechanism of the OFC in gating cocaine preference.

5.
Chem Biodivers ; : e202400557, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701359

RESUMO

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72 ± 93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

6.
Crit Rev Food Sci Nutr ; : 1-34, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712440

RESUMO

Using renewable resources for food packaging not only helps reduce our dependence on fossil fuels but also minimizes the environmental impact associated with traditional plastics. Starch has been a hot topic in the field of current research because of its low cost, wide source and good film forming property. However, a comprehensive review in this field is still lacking. Starch-based films offer a promising alternative for sustainable packaging in the food industry. The present paper covers various aspects such as raw material sources, modification methods, and film formation mechanisms. Understanding the physicochemical properties and potential commercial applications is crucial for bridging the gap between research and practical implementation. Finally, the application of starch-based films in the food industry is discussed in detail. Different modifications of starch can improve the mechanical and barrier properties of the films. The addition of active substances to starch-based films can endow them with more functions. Therefore, these factors should be better investigated and optimized in future studies to improve the physicochemical properties and functionality of starch-based films. In summary, this review provides comprehensive information and the latest research progress of starch-based films in the food industry.

7.
Front Plant Sci ; 15: 1378738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660442

RESUMO

Soil salinization poses a mounting global ecological and environmental threat. The identification of genes responsible for negative regulation of salt tolerance and their utilization in crop improvement through gene editing technologies emerges as a swift strategy for the effective utilization of saline-alkali lands. One efficient mechanism of plant salt tolerance is maintaining the proper intracellular K+/Na+ ratio. The Shaker K+ channels play a crucial role in potassium absorption, transport, and intracellular potassium homeostasis in plant cells. Here, the study presents the first genome-wide identification of Shaker K+ channels in Nicotiana tabacum L., along with a detailed bioinformatic analysis of the 20 identified members. Transcriptome analysis revealed a significant up-regulation of NtSKOR1B, an outwardly-rectifying member predominantly expressed in the root tissue of tobacco seedlings, in response to salt stress. This finding was then confirmed by GUS staining of ProNtSKOR1B::GUS transgenic lines and RT-qPCR analysis. Subsequently, NtSKOR1B knockout mutants (ntskor1) were then generated and subjected to salt conditions. It was found that ntskor1 mutants exhibit enhanced salt tolerance, characterized by increased biomass, higher K+ content and elevated K+/Na+ ratios in both leaf and root tissues, compared to wild-type plants. These results indicate that NtSKOR1B knockout inhibits K+ efflux in root and leaf tissues of tobacco seedlings under salt stress, thereby maintaining higher K+/Na+ ratios within the cells. Thus, our study identifies NtSKOR1B as a negative regulator of salt tolerance in tobacco seedlings.

8.
Toxicology ; 504: 153798, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38588857

RESUMO

Bisphenol S (BPS) is a commonly detected chemical raw material in water, which poses significant threats to both the ecological environment and human health. Despite being recognized as a typical endocrine disruptor and a substitute for Bisphenol A, the toxicological effects of BPS remain nonnegligible. In order to comprehensively understand the health impacts of BPS, a long-term (154 days) exposure experiment was conducted on mice, during which the physiological indicators of the liver, intestine, and blood were observed. The findings revealed that exposure to BPS resulted in dysbiosis of the gut microbiota, obesity, hepatic lipid accumulation, intestinal lesions, and dyslipidemia. Furthermore, there exists a significant correlation between gut microbiota and indicators of host health. Consequently, the identification of specific gut microbiota can be considered as potential biomarkers for the evaluation of risk associated with BPS. This study will effectively address the deficiency in toxicological data pertaining to BPS. The novel BPS data obtained from this research can serve as a valuable reference for professionals in the field.


Assuntos
Disbiose , Dislipidemias , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado , Obesidade , Fenóis , Sulfonas , Animais , Fenóis/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Dislipidemias/induzido quimicamente , Disbiose/induzido quimicamente , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Sulfonas/toxicidade , Disruptores Endócrinos/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/microbiologia
9.
Int Immunopharmacol ; 131: 111846, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38520787

RESUMO

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, essential for cellular communication, orchestrates a myriad of physiological and pathological processes. Recently, the intricate association between the pathway's dysregulation and the progression of malignant tumors has garnered increasing attention. Nevertheless, there is no systematic summary detailing the anticancer effects of molecules targeting the JAK/STAT pathway in the context of tumor progression. This review offers a comprehensive overview of pharmaceutical agents targeting the JAK/STAT pathway, encompassing phytochemicals, synthetic drugs, and biomolecules. These agents can manifest their anticancer effects through various mechanisms, including inhibiting proliferation, inducing apoptosis, suppressing tumor metastasis, and angiogenesis. Notably, we emphasize the clinical challenges of drug resistance while spotlighting the potential of integrating JAK/STAT inhibitors with other therapies as a transformative approach in cancer treatment. Moreover, this review delves into the avant-garde strategy of employing nanocarriers to enhance the solubility and bioavailability of anticancer drugs, significantly amplifying their therapeutic prowess. Through this academic exploration of the multifaceted roles of the JAK/STAT pathway in the cancer milieu, we aim to sketch a visionary trajectory for future oncological interventions.


Assuntos
Neoplasias , Transdução de Sinais , Humanos , Transdução de Sinais/fisiologia , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Carcinogênese
10.
BMC Pulm Med ; 24(1): 109, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438895

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) refers to the onset of breathlessness, cough, and fever at rest after arriving at high altitudes. It is a life-threatening illness caused by rapid ascent to high altitudes. Furosemide is controversial in HAPE treatment but is routinely used in China. Further research is needed to assess its efficacy and impact on HAPE management and prognosis. The aim of this study is to determine the effectiveness of furosemide for HAPE. METHODS: A retrospective was conducted to analysis of patients with HAPE admitted to the People's Hospital of Shigatse City from January 2018 to September 2023. Patients were divided into furosemide group and non-furosemide group for further analysis. Clinical variables including demographic information, comorbidities, vital signs, inflammatory markers, biochemical analysis, CT severity score and prognostic indicators were collected. RESULTS: A total of 273 patients were enrolled, with 209 patients in the furosemide group and 64 patients in the non-furosemide group. The furosemide group showed a significantly decrease in CT severity scores compared to the non-furosemide group. Subgroup analysis showed that the longer the duration of furosemide use, the more pronounced the improvement in lung CT severity scores. But there were no significant differences in length of hospital stay and in-hospital mortality between the two groups. CONCLUSION: Furosemide helps alleviate pulmonary edema in HAPE patients, but further research is needed to clarify its impact on prognosis.


Assuntos
Doença da Altitude , Furosemida , Hipertensão Pulmonar , Edema Pulmonar , Humanos , Furosemida/uso terapêutico , Altitude , Edema Pulmonar/tratamento farmacológico , Estudos Retrospectivos
11.
CNS Neurosci Ther ; 30(2): e14627, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38353058

RESUMO

BACKGROUND: Systemic inflammation in which lipopolysaccharide (LPS) is released into circulation can cause cognitive dysfunction and we have previously shown that LPS impaired working memory (WM) which refers to the ability to guide incoming behavior by retrieving recently acquired information. However, the mechanism is not very clear, and currently, there is no approved strategy to improve inflammation-induced WM deficit. Notably, epidemiological studies have demonstrated a lower occurrence rate of inflammatory-related diseases in smoking patients, suggesting that inflammation-induced WM impairment may be improved by nicotine treatment. Here, our object is to investigate the effect and potential mechanisms of acute and chronic nicotine treatment on LPS-produced WM deficiency. METHODS: Delayed alternation T-maze task (DAT) was applied for evaluating WM which includes both the short-term information storage and the ability to correct errors in adult male mice. Immunofluorescence staining and immunoblotting were used for assessing the levels and distribution of CREB-regulated transcription coactivator 1 (CRTC1) and hyperpolarization-activated cation channels 2 (HCN2) in the medial prefrontal cortex (mPFC) and hippocampus. Quantitative PCR and ELISA were employed for analyzing the mRNA and protein levels of TNF-α and IL-1ß. RESULTS: Our results revealed that administration of LPS (i.p.) at a dose of 0.5 mg/kg significantly produced WM impairment in the DAT task accompanied by an increase in IL-1ß and TNF-α expression in the mPFC. Moreover, intra-mPFC infusion of IL-1Ra, an IL-1 antagonist, markedly alleviated LPS-induced WM deficiency. More important, chronic (2 weeks) but not acute nicotine (0.2 mg/kg, subcutaneous) treatment significantly alleviated LPS-induced WM deficiency by upregulating CRTC1 and HCN2. Of note, intra-mPFC infusion of HCN blocker ZD7288 produced significant WM deficiency. CONCLUSIONS: In summary, in this study, we show that chronic nicotine treatment ameliorates acute inflammation-induced working memory deficiency by increasing CRTC1 and HCN2 in adult male mice.


Assuntos
Memória de Curto Prazo , Nicotina , Humanos , Camundongos , Masculino , Animais , Memória de Curto Prazo/fisiologia , Nicotina/farmacologia , Nicotina/uso terapêutico , Nicotina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/toxicidade , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Hipocampo/metabolismo , Fatores de Transcrição/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Canais de Potássio/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo
12.
Microbiol Spectr ; 12(2): e0317723, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38193687

RESUMO

Antimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.


Assuntos
Microbioma Gastrointestinal , Microbiota , Lactente , Criança , Humanos , Pré-Escolar , Antibacterianos/farmacologia , Bactérias/genética , Farmacorresistência Bacteriana Múltipla
13.
Cereb Cortex ; 34(1)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38163444

RESUMO

Parental feedback affects children in multiple ways. However, little is known about how children, family, and feedback types affect parental feedback neural mechanisms. The current study used functional near-infrared spectroscopy-based hyperscanning to observe 47 mother-daughter pairs's (mean age of mothers: 35.95 ± 3.99 yr old; mean age of daughters: 6.97 ± 0.75 yr old) brain synchronization in a jigsaw game under various conditions. Between parental negative feedback and praise conditions, mother-daughter brain in supramarginal gyrus, left dorsolateral prefrontal cortex, right inferior frontal gyrus, and right primary somatic (S1) differed. When criticized, conformity family-communication-patterned families had much worse brain synchronization in S1, left dorsolateral prefrontal cortex, and right Wernicke's region than conversational families. Resilient children had better mother-child supramarginal gyrus synchronicity under negative feedback. This study supports the importance of studying children's neurological development in nurturing environments to assess their psychological development.


Assuntos
Encéfalo , Córtex Pré-Frontal , Feminino , Humanos , Retroalimentação , Córtex Pré-Frontal/diagnóstico por imagem , Pais , Mães , Mapeamento Encefálico
14.
Food Chem ; 441: 138385, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38218152

RESUMO

This study investigated the effects of ß-glucan (0-6%) on the physicochemical properties, structure, and in vitro digestibility of highland barley starch (HBS) under spray drying (SD). SD significantly enhanced the inhibitory effect of 6% ß-glucan on the in vitro digestibility and glucose diffusion of HBS. After SD, the addition of ß-glucan at 4% and 6% concentration significantly increased the pasting temperatures of starch while decreased the rheological properties. Thermal properties demonstrated that ß-glucan improved the thermal stability and residue content of HBS at 600°C, lowered its maximum loss rate, and maintained its thermal stability after SD. Structural properties showed that ß-glucan affected greatly on amorphous regions of HBS after SD. Additionally, ß-glucan dispersed more evenly in the starch system and experienced hydrogen bonding with starch after SD. This study presents a novel approach to enhancing the inhibitory effect of ß-glucan on starch digestion.


Assuntos
Hordeum , beta-Glucanas , Amido/química , Hordeum/química , beta-Glucanas/química , Secagem por Atomização , Temperatura
15.
Int J Biol Macromol ; 260(Pt 1): 129417, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224806

RESUMO

The impacts of protein types and its interaction with ß-glucan on the in vitro digestibility of highland barley starch were investigated through analyzing physicochemical and microstructural properties of highland barley flour (HBF) after sequentially removing water- (WP), salt- (SP), alcohol- (AP) and alkali-soluble (AlkP) proteins. Resistant starch (RS) increased significantly in HBF after removing WP and SP, and RS of HBF was lower than that of without ß-glucan. After removing WP, SP and AP, swelling powers of HBF without ß-glucan (9.33-9.77) were higher than those of HBF (12.09-15.95). Trends of peak viscosity and peak temperature (thermal degradation temperature) were similar as swelling power, and HBF without AP showed the highest peak temperature (310.33 °C). Removals of different proteins improved the crystalline structure and short-range order of starch. There was a blue shift in T2 values and an opposite change in free water proportion. The matrix on starch surface was mainly formed by AP and AlkP, which could be aggregated by ß-glucan. But, the inhibitory effect of AP or AlkP was stronger than that of proteins combined with ß-glucan. These results help in the development of starch-based foods with different digestive properties by combining different protein types with ß-glucan.


Assuntos
Hordeum , beta-Glucanas , Amido/química , Hordeum/química , beta-Glucanas/química , Farinha , Amido Resistente , Água/química
16.
Neuroimage ; 285: 120486, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38070436

RESUMO

Early STEM education is crucial for later learning. This novel study utilised fNIRS to examine how STEM teaching methods (i.e., traditional, storytelling, storyboarding) affect neural activity synchronisation between teachers and students. Our results showed that left and right inferior frontal gyrus (IFG) for storytelling teaching versus traditional teaching, superior temporal gyrus for storyboard teaching versus traditional teaching, and left angular gyrus for storyboard and storytelling teaching were significant different in brain synchronisation. In the storytelling teaching condition, left supramarginal gyrus brain synchrony was found to improve STEM learning outcomes. In the storyboard teaching condition, IFG brain synchrony correlated positively with STEM learning improvement. The findings confirmed that story-based teaching and storyboarding can improve STEM learning efficacy at the neural level and unscored the significant role of neural synchronization as a predictor of learning outcomes.


Assuntos
Encéfalo , Aprendizagem , Criança , Humanos , Córtex Pré-Frontal , Comunicação , Lobo Temporal/diagnóstico por imagem , Mapeamento Encefálico/métodos
17.
Antioxid Redox Signal ; 40(7-9): 492-509, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37276148

RESUMO

Aims: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed excellent renoprotective effects; however, the underlying mechanism remains not fully understood. Previous studies have revealed the importance of ferroptosis, which is closely related to oxidative stress, in the progression of DKD. In the current study, we hypothesized that SGLT2i could relieve ferroptosis and thereby alleviate renal injury in DKD due to their antioxidative stress effects. Results: Typical changes of ferroptosis including massive lipid peroxidation, compromised antioxidant capability, and iron overload were found in db/db mice and high glucose/high fat (HG/HF)-treated HK-2 cells. Furthermore, increased expression of hypoxia inducible factor 1α (HIF1α) and heme oxygenase 1 (HO1) was observed in db/db mice and HG/HF-treated HK-2 cells as well. Dapagliflozin treatment significantly ameliorated the ferroptosis-related changes via attenuating overactivation of the HIF1α/HO1 axis in vivo and in vitro. Besides, downregulation of the HIF1α/HO1 axis alleviated ferroptosis, while overexpression of HIF1α and HO1 aggravated ferroptosis induced by HG/HF in HK-2 cells. Innovation and Conclusion: This study revealed that SGLT2i played a renoprotective role in DKD, at least in part, through alleviating HIF1α/HO1-mediated ferroptosis. Antioxid. Redox Signal. 40, 492-509.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Glucosídeos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Heme Oxigenase (Desciclizante) , Heme Oxigenase-1/metabolismo , Glucose/farmacologia , Hipóxia
18.
J Infect Dis ; 229(2): 376-383, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37565807

RESUMO

BACKGROUND: The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission. METHODS: To evaluate the impact of aP vaccination on the immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure. RESULTS: Multiple infections were required to elicit T-helper 17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals after a single challenge. Even after 3 challenges, T-helper 1 responses were not observed in aP-vaccinated animals. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals. CONCLUSIONS: Our results indicate that it is possible to retrain aP-primed immune responses, but it will likely require an optimal booster and multiple doses. Our results in the baboon model suggest that circulation of B. pertussis in aP-vaccinated populations is concentrated in the younger age bands of the population, providing information that can guide improved modeling of B. pertussis epidemiology in aP-vaccinated populations.


Assuntos
Coqueluche , Animais , Coqueluche/prevenção & controle , Bordetella pertussis , Papio , Anticorpos Antibacterianos , Vacina contra Coqueluche , Vacinas Acelulares
19.
Infect Immun ; 92(1): e0042123, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38047677

RESUMO

Following an oral inoculation, Chlamydia muridarum descends to the mouse large intestine for long-lasting colonization. However, a mutant C. muridarum that lacks the plasmid-encoded protein pGP3 due to an engineered premature stop codon (designated as CMpGP3S) failed to do so even following an intrajejunal inoculation. This was because a CD4+ T cell-dependent immunity prevented the spread of CMpGP3S from the small intestine to the large intestine. In the current study, we found that mice deficient in IL-22 (IL-22-/-) allowed CMpGP3S to spread from the small intestine to the large intestine on day 3 after intrajejunal inoculation, indicating a critical role of IL-22 in regulating the chlamydial spread. The responsible IL-22 is produced by CD4+ T cells since IL-22-/- mice were rescued to block the CMpGP3S spread by donor CD4+ T cells from C57BL/6J mice. Consistently, CD4+ T cells lacking IL-22 failed to block the spread of CMpGP3S in Rag2-/- mice, while IL-22-competent CD4+ T cells did block. Furthermore, mice deficient in cathelicidin-related antimicrobial peptide (CRAMP) permitted the CMpGP3S spread, but donor CD4+ T cells from CRAMP-/- mice were still sufficient for preventing the CMpGP3S spread in Rag2-/- mice, indicating a critical role of CRAMP in regulating chlamydial spreading, and the responsible CRAMP is not produced by CD4+ T cells. Thus, the IL-22-producing CD4+ T cell-dependent regulation of chlamydial spreading correlated with CRAMP produced by non-CD4+ T cells. These findings provide a platform for further characterizing the subset(s) of CD4+ T cells responsible for regulating bacterial spreading in the intestine.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Interleucina 22 , Linfócitos T , Animais , Camundongos , Linfócitos T CD4-Positivos , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/microbiologia , Chlamydia muridarum/fisiologia , Interleucina 22/imunologia , Intestino Grosso , Intestino Delgado , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia
20.
Eur J Immunol ; 54(4): e2250281, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37937817

RESUMO

Vitiligo is a disease featuring distinct white patches that result from melanocyte destruction. The overall pathogenesis of vitiligo remains to be elucidated. Nevertheless, considerable research indicates that adaptive immune activation plays a key role in this process. Specifically, the interferon-gamma (IFN-γ), C-X-C motif chemokine ligands (CXCL9/10), and C-X-C motif chemokine receptor (CXCR3) signaling axis, collectively referred to as IFN-γ-CXCL9/10-CXCR3 or ICC axis, has emerged as a key mediator responsible for the recruitment of autoimmune CXCR3+ CD8+ T cells. These cells serve as executioners of melanocytes by promoting their detachment and apoptosis. Moreover, IFN-γ is generated by activated T cells to create a positive feedback loop, exacerbating the autoimmune response. This review not only delves into the mechanistic insights of the ICC axis but also explores the significant immunological effects of associated cytokines and their receptors. Additionally, the review provides a thorough comparison of existing and emerging treatment options that target the ICC axis for managing vitiligo. This review aims to foster further advancements in basic research within related fields and facilitate a deeper understanding of alternative treatment strategies targeting different elements of the axis.


Assuntos
Vitiligo , Humanos , Vitiligo/terapia , Linfócitos T CD8-Positivos , Interferon gama , Quimiocina CXCL10 , Quimiocina CXCL9 , Receptores CXCR3
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA