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1.
Nat Ment Health ; 2(9): 1084-1095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39263364

RESUMO

Risk evaluation is ubiquitous in decisions. Deep brain stimulation of the subthalamic nucleus is effective for Parkinson's disease and obsessive-compulsive disorder, and can be associated with impulsivity and hypomania. Subthalamic stimulation has seemingly contrasting effects on impulsivity enhancing conflict-induced impulsivity but decreasing risk taking. Here, using a card gambling task paired with intracranial recordings (n = 25) and within-subject case control acute stimulation (n = 15) of the right subthalamic nucleus, we dissociated objective risk and uncertainty and subjective physiological markers of risk. Acute stimulation decreased risk taking (P = 0.010, Cohen's d = 0.72) and increased subthalamic theta activity (P < 0.001, Cohen's d = 0.72). Critically, stimulation negatively shifted the relationship between subthalamic physiology and a measure of evidence accumulation similar to observations with stimulation-induced conflict processing. This highlights the phenotypic and physiological heterogeneity of impulsivity, yet linking mechanisms underlying stimulation-induced conflict and risk. Finally, stimulation-induced risk seeking implicates the ventral subthalamic nucleus and dissociating anatomical and functional connectivity with the mesial prefrontal cortex. Our findings have implications for conceptualizations of impulsivity, and clinical relevance for neuropsychiatric disorders.

2.
Int J Food Microbiol ; 422: 110814, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-38972103

RESUMO

Ohmic heating (OH), an emerging food processing technology employed in the food processing industry, raises potential food safety concerns due to the recovery of sublethally injured pathogens such as Staphylococcus aureus (S. aureus). In the present study, sensitivity to various stress conditions and the changes in cellular-related factors of OH-injured S. aureus during repair were investigated. The results indicated that liquid media differences (nutrient broth (NB), phosphate-buffered saline (PBS), milk, and cucumber juice) affected the recovery process of injured cells. Nutrient enrichment determines the bacterial repair rate, and the rates of repair for these media were milk > NB > cucumber juice > PBS. The sensitivity of injured cells to various stressors, including different acids, temperature, nisin, simulated gastric fluid, and bile salt, increased during the injury phase and subsequently diminished upon repair. Additionally, the intracellular ATP content, enzyme activities (Na+/K+-ATPase, Ca2+/Mg2+-ATPase, and T-ATPase) and ion concentrations (Mg2+, K+, and Ca2+) gradually increased during repair. After 5 h of repair, the intracellular substances content of cell's was significantly higher than that of the injured bacteria without repair, while some indicators (e.g., Na+/K+-ATPase, K+, and Ca2+) were not restored to the untreated level. The results of this study indicated that OH-injured S. aureus exhibited strengthened resistance post-recovery, potentially due to the restoration of cellular structures. These findings have implications for optimizing food storage conditions and advancing OH processes in the food industry.


Assuntos
Manipulação de Alimentos , Temperatura Alta , Staphylococcus aureus , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Estresse Fisiológico , Trifosfato de Adenosina/metabolismo
3.
Brain Stimul ; 17(3): 713-720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38839040

RESUMO

BACKGROUND: Recent studies indicate that both prefrontal and visual regions play critical roles in visual working memory (VWM), with prefrontal regions mainly associated with executive functions, and visual cortices linked to representations of memory contents. VWM involves the selective filtering of irrelevant information, yet the specific contributions of the prefrontal regions and visual cortex in this process remain unclear. OBJECTIVE: To understand the dynamic causal roles of prefrontal and visual regions in VWM. METHODS: The differentiation of VWM components was achieved using a computational model that incorporated a swap rate for non-target stimuli. Single-pulse magnetic transcranial stimulation (spTMS) was delivered to the early visual cortex (EVC) and the inferior frontal junction (IFJ) across different phases of an orientation recall task that with or without distractors. RESULTS: Our results indicate that spTMS over the EVC and IFJ influences VWM particularly when distractors are present. VWM precision can be impacted by spTMS applied to either region during the early retention, while spTMS effect is especially prominent when EVC is stimulated during the late retention phase and when directed at the ipsilateral EVC. Conversely, the probability of accurately recalling the target exhibited comparable patterns when spTMS was administered to either the EVC or IFJ. CONCLUSIONS: We highlight the "sensory recruitment" of VWM characterized by critical involvement of EVC particularly in the information-filtering process within VWM. The maintenance of memory content representations necessitates ongoing communication between the EVC and IFJ throughout the entirety of the VWM process in a dynamic pattern.


Assuntos
Memória de Curto Prazo , Estimulação Magnética Transcraniana , Córtex Visual , Percepção Visual , Humanos , Memória de Curto Prazo/fisiologia , Estimulação Magnética Transcraniana/métodos , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Masculino , Adulto , Feminino , Córtex Pré-Frontal/fisiologia , Rememoração Mental/fisiologia , Adulto Jovem
4.
Gen Psychiatr ; 37(3): e101210, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912307

RESUMO

Background: Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD). Aims: The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD. Methods: Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations. Results: Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age. Conclusions: Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

5.
Heliyon ; 10(7): e28645, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596085

RESUMO

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

8.
Int J Food Microbiol ; 410: 110483, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37995495

RESUMO

Ohmic heating (OH), an innovative heating technology, presents potential applications in the pasteurization of liquid foods. Therefore, the study was conducted to evaluate the effect of OH at various voltage gradients (10 V/cm, 12.5 V/cm, and 15 V/cm) and water bath (WB) on microbial inactivation, physicochemical and sensory properties and microbial flora of pasteurized milk. Results indicated that OH with higher voltage could effectively inactivate microorganisms in milk, requiring less heating time and energy. Moreover, OH treatment at higher voltages could decelerate lipid oxidation and better maintain the sensory quality and essential amino acids content of milk. Additionally, all treatments significantly altered the microbial community, and during storage, the microbial community in milk treated with 10 V/cm and 12.5 V/cm OH remained relatively stable. OH treatments with voltage gradients exceeding 12.5 V/cm could effectively inactive microorganisms and maintain the quality attributes of milk.


Assuntos
Calefação , Leite , Animais , Leite/química , Temperatura Alta , Pasteurização/métodos , Viabilidade Microbiana
9.
Geriatr Nurs ; 55: 255-262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38091711

RESUMO

OBJECTIVE: To explore the efficacy of game training combined with surface electromyography biofeedback (sEMG-BF) in the treatment of dysphagia after early stroke. METHODS: Ninety patients with early post-stroke dysphagia (PSD), who were diagnosed and treated from March 2021 to December 2022, were divided randomly into a control group (30 cases), experimental group 1 (30 cases) and experimental group 2 (30 cases). The control group received routine swallowing rehabilitation and transcranial direct current stimulation. Experimental group 1 received sEMG-BF in conjunction with the care provided to the control group. Experimental group 2 received sEMG-BF and game training in addition to the care provided to the control group. Before and after treatment, all three patient groups were evaluated using the WADA water swallowing test, the Functional Oral Intake Scale (FOIS), sEMG and a tongue manometer test. RESULTS: Before treatment, there was no significant difference (P > 0.05) among the three groups of patients in terms of WADA water swallowing rating, FOIS score, submandibular muscle sEMG peak, swallowing time limit and maximum tongue pressure. After treatment, all three groups exhibited improvements in these indices compared with those before treatment (P < 0.05). Experimental group 1 showed greater improvement than the control group (P < 0.05), and experimental group 2 exhibited greater improvement than experimental group 1 and the control group (P < 0.05). CONCLUSION: Game training combined with sEMG-BF can significantly improve the swallowing function of patients with PSD.


Assuntos
Transtornos de Deglutição , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Eletromiografia , Pressão , Resultado do Tratamento , Língua , Acidente Vascular Cerebral/complicações , Biorretroalimentação Psicológica , Água
10.
Sci Total Environ ; 912: 168905, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38016549

RESUMO

In traditional CRISPR-based biosensors, the cleavage-induced signal generation is insufficient because only a signals is generated at a CRISPR-induced cleavage. Herein, we developed an improved CRISPR/Cas12a-based biosensor with an enlarged signal generation which integrated the hybridization chain reaction (HCR) and low-background Förster Resonance Energy Transfer (FRET) signal output mode. The HCR with nucleic acid self-assembly capability was used as a signal carrier to load more signaling molecules. To get the best signal amplification, three different fluorescence signal output modes (fluorescence recovery, FRET and low-background FRET) generated by two fluoresceins, FAM and Cy5, were fully investigated and compared. The results indicated that the low-background FRET signal output mode with the strictest signal generation conditions yielded the highest signal-to-noise ratio (S/N) (19.17) and the most obvious fluorescence color change (from red to yellow). In optimal conditions, the proposed biosensor was successfully applied for Salmonella Typhimurium (S. Typhimurium) detection with 6 h (including 4 h for sample pre-treatment) from the initial target processing to the final detection result. The qualitative sensitivity, reliant on color changes, was 103 CFU/mL. The quantitative sensitivity, calculated by the fluorescence value, were 1.62 × 101 CFU/mL, 3.72 × 102 CFU/mL, and 8.71 × 102 CFU/mL in buffer solution, S. Typhimurium-spiked milk samples, and S.Typhimurium-spiked chicken samples, respectively. The excellent detection performance of the proposed biosensor endowed its great application potential in food and environment safety monitoring.


Assuntos
Técnicas Biossensoriais , Salmonella typhimurium , Técnicas Biossensoriais/métodos , Hibridização de Ácido Nucleico , Fluoresceínas , Hibridização Genética
11.
J Clin Exp Neuropsychol ; 45(6): 606-617, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37916529

RESUMO

INTRODUCTION: Previous research showed that methadone maintenance treatment (MMT) is linked to impulsivity, with higher impulsivity levels being associated with for example, increased drug use. One aspect of impulsivity, most commonly studied in rodent research, is premature responding, the failure to wait for a starting signal. Premature responding is of high translational significance since it predicts the development of addiction-like behaviors in rodents. METHODS: We assessed 45 MMT patients and 46 demographically matched (age, sex, education, and handedness) healthy volunteers (HVs) on premature responding alongside action and inhibition of instructed and intentional trials using the Intentional Hand Task (IHT). RESULTS: The results showed markedly enhanced premature responses in the MMT vs. the HV group, which correlated positively with methadone dosage in the MMT patients. Throughout the task, MMT patients were faster across all trial parts and less accurate in response to instructed trials compared to HVs. CONCLUSIONS: The increase in premature motor reactions during variable waiting periods alongside increased motion speed and lower accuracy might reflect a specific motor inhibition deficit in MMT, a subcomponent of impulsivity not previously assessed in MMT. Incorporating an experimentally defined measure of impulsivity, such as premature responding, into existing test batteries used by clinicians might enable more tailored treatments addressing the increased impulsivity levels and associated dysfunctional behaviors in MMT.


Assuntos
Dependência de Heroína , Metadona , Humanos , Lateralidade Funcional , Voluntários Saudáveis , Dependência de Heroína/reabilitação , Comportamento Impulsivo , Metadona/uso terapêutico , Masculino , Feminino
12.
Cell Death Dis ; 14(11): 717, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923734

RESUMO

Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates hypercoagulability via negative modulation of fibrinogen expression. We demonstrated that GRSF1 negatively regulated fibrinogen expression at both mRNA and protein levels. GRSF1 directly interacted with the coding region (CDS) of FGA, FGB, and FGG mRNAs, and decreased their stability thus mitigating fibrinogen expression. We further identified that only a few G-tracts within the Fib C domain of FGA, FGB, and FGG CDS and the qRRM2 domain of GRSF1 were required for their interaction. Moreover, we confirmed hypercoagulability and the decrease of GRSF1 expression level during mice aging. Functionally, GRSF1 overexpression in old mice liver decreased fibrinogen plasma level, reduced hypercoagulability, and mitigated blood coagulation activity, whereas GRSF1 knockdown in young mice liver increased fibrinogen plasma level and promoted blood coagulation activity. Collectively, our findings unveil a novel posttranscriptional regulation of fibrinogen by GRSF1 and uncover a critical role of GRSF1 in regulating blood coagulation activity.


Assuntos
Fibrinogênio , Trombofilia , Idoso , Animais , Humanos , Camundongos , Fibrinogênio/genética , Fibrinogênio/metabolismo , Regulação da Expressão Gênica , Proteínas de Ligação a Poli(A)/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Food Res Int ; 173(Pt 1): 113204, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803533

RESUMO

As an emerging food processing technology, cold atmospheric plasma (CAP) has attracted great attention in the field of microbial inactivation. Although CAP has been proven to effectively inactivate a variety of foodborne pathogens, there is less research on the inactivation of Bacillus cereus, and the exact inactivation mechanism is still unclear. Elucidating the inactivation mechanism will help to develop and optimize this sterilization method, with the prospective application in industrialized food production. This study aims to explore the bactericidal efficacy difference between air and nitrogen CAP on B. cereus, a typical Gram-positive bacterium, and reveals the inactivation mechanism of CAP at the cellular and molecular level, by observing the change of the cell membrane, cell morphological damage, intracellular antioxidant enzyme activity and cellular biomacromolecules changes. The results showed that both air CAP and nitrogen CAP could effectively inactivate B. cereus, which was due to the reactive oxygen and nitrogen species (RONS) generated by the plasma causing bacterial death. The damage pathways of CAP on Gram-positive bacteria could be explained by disrupting the bacterial cell membrane and cell morphology, disturbing the intracellular redox homeostasis, and destroying biomacromolecules in the cells. The differences in active species generated by the plasma were the main reason for the different bactericidal efficiencies of air CAP and nitrogen CAP, where air CAP producing RONS with stronger oxidative capacity in a shorter time. This study indicates that air CAP is an effective, inexpensive and green technology for B. cereus inactivation, providing a basis for industrial application in food processing.


Assuntos
Bacillus cereus , Gases em Plasma , Gases em Plasma/farmacologia , Nitrogênio , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Espécies Reativas de Oxigênio
14.
Appl Environ Microbiol ; 89(11): e0095023, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37882529

RESUMO

IMPORTANCE: Plant protection products are essential for ensuring food production, but their use poses a threat to human and environmental health, and their efficacy is decreasing due to the acquisition of resistance by pathogens. Stricter regulations and consumer demand for cleaner produce are driving the search for safer and more sustainable alternatives. Microbial biocontrol agents, such as microorganisms with antifungal activity, have emerged as a promising alternative management strategy, but their commercial use has been limited by poor establishment and spread on crops. This study presents a novel system to overcome these challenges. The biocontrol agent Lactiplantibacillus plantarum AMBP214 was spray-dried and successfully dispersed to strawberry flowers via bumblebees. This is the first report of combining spray-dried, non-spore-forming bacteria with pollinator-dispersal, which scored better than the state-of-the-art in terms of dispersal to the plant (CFU/flower), and resuscitation of the biocontrol agent. Therefore, this new entomovectoring system holds great promise for the use of biocontrol agents for disease management in agriculture.


Assuntos
Fragaria , Controle Biológico de Vetores , Animais , Abelhas , Humanos , Produtos Agrícolas , Fragaria/microbiologia
15.
BMC Biol ; 21(1): 194, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704988

RESUMO

BACKGROUND: Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness. RESULTS: A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity. CONCLUSIONS: This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.


Assuntos
Aedes , Vírus da Dengue , Inseticidas , Infecção por Zika virus , Zika virus , Animais , Aedes/genética , Vírus da Dengue/genética , Inseticidas/farmacologia , Mosquitos Vetores/genética
16.
NPJ Sci Learn ; 8(1): 27, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37567915

RESUMO

It is said that our species use mnemonics - that "magic of memorization" - to engrave an enormous amount of information in the brain. Yet, it is unclear how mnemonics affect memory and what the neural underpinnings are. In this electroencephalography study, we examined the hypotheses whether mnemonic training improved processing-efficiency and/or altered encoding-pattern to support memory enhancement. By 22-day training of a digit-image mnemonic (a custom memory technique used by world-class mnemonists), a group of children showed increased short-term memory after training, but with limited gain generalization. This training resulted in regular odd-even neural patterns (i.e., enhanced P200 and theta power during the encoding of digits at even- versus odd- positions in a sequence). Critically, the P200 and theta power effects predicted the training-induced memory improvement. These findings provide evidence of how mnemonics alter encoding pattern, as reflected in functional brain organization, to support memory enhancement.

17.
J Am Soc Mass Spectrom ; 34(10): 2407-2412, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37552044

RESUMO

Selected ion flow tube-mass spectrometry (SIFT-MS) is an analytical technique for volatile detection and quantification. SIFT-MS can be applied in a "white box" approach, measuring concentrations of target compounds, or as a "black box" fingerprinting technique, scanning all product ions during a full scan. Combining SIFT-MS full scan data acquired from multibatches or large-scale experiments remains problematic due to signal fluctuation over time. The standard approach of normalizing full scan data to the total signal intensity was insufficient. This study proposes a new approach to correct SIFT-MS fingerprinting data. In this concept, all of the product ions from a full scan are considered individual compounds for which notional concentrations can be calculated. Converting ion count rates into notional analyte concentrations accounts for any changes in the instrument parameters. The benefits of the proposed approach are demonstrated on three years of data from both multibatches and long-term experiments showing a significant reduction of system-induced fluctuations providing a better focus on the changes of interest.

18.
Neoplasma ; 70(3): 402-415, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37498068

RESUMO

The regulation of protein kinase B (AKT) phosphorylation by Tripartite motif-containing protein 31 (TRIM31) is implicated as an essential mechanism in the progression of many malignant tumors. Nevertheless, the function of the TRIM31/AKT pathway in oral squamous cell carcinoma (OSCC) remains elusive. Here, immunohistochemistry analysis of human OSCC tissue microarrays indicated significantly higher levels of TRIM31 and phosphorylated AKT (p-AKT) in OSCC tumors than in adjacent tissue samples. Also, we detected a positive association between TRIM31 expression and clinical OSCC development. In in vitro studies, TRIM31 knockdown severely impaired OSCC cell growth, invasion, and migration. By contrast, TRIM31 overexpression improved these cell behaviors, while subsequent AKT inhibition abrogated the effect. In vivo tumorigenesis experiments using nude mice also validated the effects of TRIM31/AKT signaling in tumor growth. Furthermore, TRIM31 upregulation facilitated glucose uptake, as well as lactate and adenosine triphosphate production of OSCC cells, while such positive effects on glycolysis and malignant cell phenotypes were reversed by treatment with AKT or glycolysis inhibitors. In conclusion, TRIM31 may improve OSCC progression by enhancing AKT phosphorylation and subsequent glycolysis. Hence, TRIM31 has the potential as a treatment target in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Glicólise , Camundongos Nus , Neoplasias Bucais/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética
19.
Front Pharmacol ; 14: 1191692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435494

RESUMO

Introduction: Sjögren's syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology. Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy. Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice. Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment.

20.
Int J Food Microbiol ; 402: 110313, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37421873

RESUMO

Botrytis cinerea is a devastating pathogen that can cause huge postharvest losses of strawberry. Although this fungus usually infects strawberries through their flowers, symptoms mainly appear when fruit are fully mature. A fast and sensitive method to detect and quantify the fungal infection, prior to symptom development, is, therefore, needed. In this study, we explore the possibility of using the strawberry volatilome to identify biomarkers for B. cinerea infection. Strawberry flowers were inoculated with B. cinerea to mimic the natural infection. First, quantitative polymerase chain reaction (qPCR) was used to quantify B. cinerea in the strawberry fruit. The detection limit of qPCR for B. cinerea DNA extracted from strawberries was 0.01 ng. Subsequently, changes in the fruit volatilome at different fruit developmental stages were characterized using gas chromatography - mass spectrometry (GC-MS) and selected ion flow tube mass spectrometry (SIFT-MS). Based on GC-MS data, 1-octen-3-ol produced by B. cinerea was confirmed as a potential biomarker of B. cinerea infection. Moreover, the product ion NO+ 127, obtained by SIFT-MS measurements, was proposed as a potential biomarker for B. cinerea infection by comparing its relative level with that of 1-octen-3-ol (obtained by GC-MS) and B. cinerea (obtained by qPCR). Separate PLS regressions were carried out for each developmental stages, and 11 product ions were significantly altered at all developmental stages. Finally, PLS regressions using these 11 ions as variables allowed the discrimination between samples containing different amount of B. cinerea. This work showed that profiling the fruit's volatilome using SIFT-MS can be used as a potential alternative to detect B. cinerea during the quiescent stage of B. cinerea infection prior to symptom development. Moreover, the corresponding compounds of potential biomarkers suggest that the volatile changes caused by B. cinerea infection may contribute to strawberry defense.


Assuntos
Fragaria , Fragaria/microbiologia , Frutas/microbiologia , Espectrometria de Massas , Botrytis , Doenças das Plantas/microbiologia
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