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1.
BMC Cancer ; 24(1): 684, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840087

RESUMO

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Imunoterapia/métodos , Fatores de Tempo , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Masculino , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Ipilimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Surg Case Rep ; 2024(6): rjae391, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38835947

RESUMO

The radial forearm free flap (RFFF) is a workhorse flap for head and neck reconstruction. We present an unusual case of radial artery occlusion, likely from previous transradial cardiac catheterization, in a patient for whom an RFFF was raised for floor of mouth reconstruction following resection of squamous cell carcinoma. Pre-operative assessment with ultrasound Doppler and an Allen test was normal. The flap was raised uneventfully under tourniquet control. However, following flap elevation and tourniquet release, poor flap perfusion was noted, and cutback of the artery revealed a long segment of hard fibrous plaque within the lumen. Retrospective review of medical records showed a history of cardiac catheterization via the same radial artery. We discuss various measures that can prevent this occurrence, including careful pre-operative screening of previous procedures involving the radial artery, the reverse Allen test, Doppler ultrasound, and consideration of distal arterial exploration without a tourniquet.

4.
J Clin Nurs ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837508

RESUMO

AIM: To investigate the real-world experiences of nurses' using smart glasses to triage patients in an urgent care centre. DESIGN: A parallel convergent mixed-method design. METHODS: We collected data through twelve in-depth interviews with nurses using the device and a survey. Recruitment continued until no new themes emerged. We coded the data using a deductive-thematic approach. Qualitative and survey data were coded and then mapped to the most dominant dimension of the sociotechnical framework. Both the qualitative and quantitative findings were triangulated within each dimension of the framework to gain a comprehensive understanding of user experiences. RESULTS: Overall, nurses were satisfied with using smart glasses in urgent care and would recommend them to others. Nurses rated the device highly on ease of use, facilitation of training and development, nursing empowerment and communication. Qualitatively, nurses generally felt the device improved workflows and saved staff time. Conversely, technological challenges limited its use, and users questioned its sustainability if inadequate staffing could not be resolved. CONCLUSION: Smart glasses enhanced urgent care practices by improving workflows, fostering staff communication, and empowering healthcare professionals, notably providing development opportunities for nurses. While smart glasses offered transformative benefits in the urgent care setting, challenges, including technological constraints and insufficient organisational support, were barriers to sustained integration. IMPLICATIONS FOR PRACTICE: These real-world insights encompass both the benefits and challenges of smart glass utilisation in the context of urgent care. The findings will help inform greater workflow optimisation and future technological developments. Moreover, by sharing these experiences, other healthcare institutions looking to implement smart glass technology can learn from the successes and barriers encountered, facilitating smoother adoption, and maximising the potential benefits for patient care. REPORTING METHOD: COREQ checklist (consolidated criteria for reporting qualitative research). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

5.
Cancer Lett ; 597: 217023, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852701

RESUMO

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.

6.
Mol Neurobiol ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823000

RESUMO

In this study, we aimed to work through the key genes involved in the process of pyroptosis in Alzheimer's disease (AD) to identify potential biomarkers using bioinformatics technology and further explore the underlying molecular mechanisms. The transcriptome data of brain tissue in AD patients were screened from the GEO database, and pyroptosis-related genes were analyzed. The functions of differential genes were analyzed by enrichment analysis and protein-protein interaction. The diagnostic model was established using LASSO and logistic regression analysis, and the correlation of clinical data was analyzed. Based on single-cell analysis of brain tissues of patients with AD, immunofluorescence and western blotting were used to explore the key cells affected by the hub gene. After GSEA, qRT-PCR, western blotting, LDH, ROS, and JC-1 were used to investigate the potential mechanism of the hub gene on pyroptosis. A total of 15 pyroptosis differentially expressed genes were identified. A prediction model consisting of six genes was established by LASSO and logistic regression analysis, and the area under the curve was up to 0.81. As a hub gene, CHMP4B was negatively correlated with the severity of AD. CHMP4B expression was decreased in the hippocampal tissue of patients with AD and mice. Single-cell analysis showed that CHMP4B was downregulated in AD microglia. Overexpression of CHMP4B reduced the release of LDH and ROS and restored mitochondrial membrane potential, thereby alleviating the inflammatory response during microglial pyroptosis. In summary, CHMP4B as a hub gene provides a new strategy for the diagnosis and treatment of AD.

8.
JMIR Res Protoc ; 13: e56081, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865699

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a devastating condition that often leads to significant impairments in physical function, leading to disability and mental health disorders. Hence, understanding the prevalence of SCI and the relationship between physical activity and mental health in individuals with SCI is crucial for informing rehabilitation strategies and optimizing outcomes. OBJECTIVE: This study aims to comprehensively analyze existing research on the link between physical activity and mental health and identify the level of physical activity and mental health status, the barriers to physical activity, and SCI's impacts on psychological well-being in individuals with SCI. METHODS: An electronic search strategy will be used to identify prevalence studies published since 1993 in health-related databases such as PubMed, MEDLINE, COCHRANE Library, and Wiley Library using the following query: "Spinal Cord Injury" OR "Paraplegia" OR "Tetraplegia" AND "Physical Activity" OR "Exercise" AND "Mental Health" OR "Mental Illness" OR "Mental Disorder." Bibliographies of primary studies and review articles meeting the inclusion criteria will be searched manually to identify further eligible studies. The risk of bias in the included studies will be appraised using the Joanna Briggs Institute checklist for prevalence studies by 2 review authors. Any disagreement will be resolved by reaching a consensus. RESULTS: Funding was received in October 2023, data collection will commence in July 2024, and the results are expected by 2025. We will summarize the selection of the eligible studies using a flowchart. The data from the studies will be extracted and tabulated. This scoping review will be published in a peer-reviewed journal in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. CONCLUSIONS: This scoping review underscores the complex relationship between physical activity and mental health among individuals with SCI, highlighting the level of physical activity and mental health status, barriers to physical activity engagement, and psychological implications. Understanding these dynamics is crucial in devising tailored interventions aimed at enhancing mental well-being. This synthesis of evidence emphasizes the need for personalized strategies to promote physical activity, addressing unique challenges faced by this population to foster improved mental health outcomes and overall quality of life. TRIAL REGISTRATION: Open Science Framework osf.io/ugx7d; https://osf.io/ugx7d/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56081.


Assuntos
Exercício Físico , Saúde Mental , Traumatismos da Medula Espinal , Humanos , Exercício Físico/psicologia , Traumatismos da Medula Espinal/psicologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/epidemiologia , Revisões Sistemáticas como Assunto
9.
Top Cogn Sci ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781432

RESUMO

One important goal of cognitive science is to understand the mind in terms of its representational and computational capacities, where computational modeling plays an essential role in providing theoretical explanations and predictions of human behavior and mental phenomena. In my research, I have been using computational modeling, together with behavioral experiments and cognitive neuroscience methods, to investigate the information processing mechanisms underlying learning and visual cognition in terms of perceptual representation and attention strategy. In perceptual representation, I have used neural network models to understand how the split architecture in the human visual system influences visual cognition, and to examine perceptual representation development as the results of expertise. In attention strategy, I have developed the Eye Movement analysis with Hidden Markov Models method for quantifying eye movement pattern and consistency using both spatial and temporal information, which has led to novel findings across disciplines not discoverable using traditional methods. By integrating it with deep neural networks (DNN), I have developed DNN+HMM to account for eye movement strategy learning in human visual cognition. The understanding of the human mind through computational modeling also facilitates research on artificial intelligence's (AI) comparability with human cognition, which can in turn help explainable AI systems infer humans' belief on AI's operations and provide human-centered explanations to enhance human-AI interaction and mutual understanding. Together, these demonstrate the essential role of computational modeling methods in providing theoretical accounts of the human mind as well as its interaction with its environment and AI systems.

10.
Antioxidants (Basel) ; 13(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38790643

RESUMO

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

11.
Sci Rep ; 14(1): 12386, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811720

RESUMO

Triple-negative breast cancer (TNBC) has high heterogeneity, poor prognosis, and limited treatment success. Recently, an immunohistochemistry-based surrogate classification for the "Fudan University Shanghai Cancer Center (FUSCC) subtyping" has been developed and is considered more suitable for clinical application. Seventy-one paraffin-embedded sections of surgically resected TNBC were classified into four molecular subtypes using the IHC-based surrogate classification. Genomic analysis was performed by targeted next-generation sequencing and the specificity of the subtypes was explored by bioinformatics, including survival analysis, multivariate Cox regression, pathway enrichment, Pyclone analysis, mutational signature analysis and PHIAL analysis. AKT1 and BRCA1 mutations were identified as independent prognostic factors in TNBC. TNBC molecular subtypes encompass distinct genomic landscapes that show specific heterogeneities. The luminal androgen receptor (LAR) subtype was associated with mutations in PIK3CA and PI3K pathways, which are potentially sensitive to PI3K pathway inhibitors. The basal-like immune-suppressed (BLIS) subtype was characterized by high genomic instability and the specific possession of signature 19 while patients in the immunomodulatory (IM) subtype belonged to the PD-L1 ≥ 1% subgroup with enrichment in Notch signaling, suggesting a possible benefit of immune checkpoint inhibitors and Notch inhibitors. Moreover, mesenchymal-like (MES) tumors displayed enrichment in the receptor tyrosine kinase (RTK)-RAS pathway and potential sensitivity to RTK pathway inhibitors. The findings suggest potential treatment targets and prognostic factors, indicating the possibility of TNBC stratified therapy in the future.


Assuntos
Mutação , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Prognóstico , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Genômica/métodos , Proteína BRCA1/genética , Adulto , Biomarcadores Tumorais/genética , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo
12.
Am J Nurs ; 124(6): 64, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38780347

RESUMO

Understanding the true shock of a patient's diagnosis.

13.
JMIR Public Health Surveill ; 10: e55211, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713911

RESUMO

BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.


Assuntos
Disfunção Cognitiva , Demência , Descanso , Humanos , Feminino , Masculino , Disfunção Cognitiva/epidemiologia , Pessoa de Meia-Idade , Idoso , Demência/epidemiologia , Estudos Prospectivos , Descanso/fisiologia , Adulto , Reino Unido/epidemiologia , Actigrafia , Fatores de Risco , Ritmo Circadiano/fisiologia
14.
Phytochemistry ; 224: 114140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38750709

RESUMO

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.


Assuntos
Alcaloides , Fritillaria , Raízes de Plantas , Fritillaria/química , Raízes de Plantas/química , Estrutura Molecular , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Cevanas/química , Cevanas/farmacologia , Cevanas/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Animais , Conformação Molecular , Cristalografia por Raios X , Linhagem Celular , Ratos , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Modelos Moleculares
15.
J Obes Metab Syndr ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38714326

RESUMO

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indexes of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indexes shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion: This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

16.
Vet Q ; 44(1): 1-13, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38712855

RESUMO

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.


Assuntos
Antivirais , Coronavirus Felino , Peritonite Infecciosa Felina , Lactamas , Leucina/análogos & derivados , Extratos Vegetais , Ácidos Sulfônicos , Vigna , Coronavirus Felino/efeitos dos fármacos , Antivirais/farmacologia , Animais , Extratos Vegetais/farmacologia , Gatos , Peritonite Infecciosa Felina/tratamento farmacológico , Peritonite Infecciosa Felina/virologia , Vigna/química , Replicação Viral/efeitos dos fármacos , Linhagem Celular
18.
Int J Biol Macromol ; 268(Pt 2): 131779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679250

RESUMO

Natto contains a potent fibrinolytic enzyme called nattokinase (NK), which has thrombolytic, antihypertensive, antiatherosclerotic and lipid-lowering effects. Although NK has been recognized for its beneficial effect on humans with atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms involved in vascular inflammation-atherosclerosis development remain largely unknown. The current study aimed to explore the effects of NK on gene regulation, autophagy, necroptosis and inflammasome in vascular inflammation. The transcriptional profiles of NK in endothelial cells (ECs) by RNA sequencing (RNA-seq) revealed that NK affected THBS1, SRF and SREBF1 mRNA expression. In Q-PCR analysis, SRF and THBS1 were upregulated but SREBF1 was unaffected in ECs treated with NK. NK treatment induced autophagy and inhibited NLRP3 inflammasome and necroptosis in ECs. Furthermore, the inhibition of SRF or THBS1 by siRNA suppressed autophagy and enhanced the NLRP3 inflammasome and necroptosis. In a mouse model, NK reduced vascular inflammation by activating autophagy and inhibiting NLRP3 inflammasome and necroptosis. Our findings provide the first evidence that NK upregulates SRF and THBS1 genes, subsequently increasing autophagy and decreasing necroptosis and NLRP3 inflammasome formation to reduce vascular inflammation. Therefore, NK could serve as nutraceuticals or adjuvant therapies to reduce vascular inflammation and possible atherosclerosis progression.


Assuntos
Inflamação , Subtilisinas , Trombospondina 1 , Animais , Masculino , Camundongos , Autofagia/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamassomos/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Subtilisinas/metabolismo , Trombospondina 1/metabolismo , Trombospondina 1/genética , Camundongos Endogâmicos C57BL
19.
Int J Med Sci ; 21(5): 784-794, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617006

RESUMO

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.


Assuntos
Síndrome de Bardet-Biedl , Insuficiência Renal Crônica , Feminino , Masculino , Humanos , Síndrome de Bardet-Biedl/epidemiologia , Síndrome de Bardet-Biedl/genética , Comorbidade , Heterozigoto , Obesidade/epidemiologia , Obesidade/genética , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/genética
20.
J Dent Sci ; 19(2): 1028-1035, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618058

RESUMO

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

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