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1.
Exp Dermatol ; 33(6): e15108, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855891

RESUMO

Head and neck atopic dermatitis (HNAD) is a subtype of atopic dermatitis (AD), a common inflammatory skin condition with a distinctive clinical appearance. Malassezia spp., a predominant skin yeast, is considered to exacerbate HNAD. In this study, we investigate the prevalence of Malassezia-specific IgE among HNAD patients. A comprehensive search was performed for observational studies analysing the association between Malassezia-specific IgE and HNAD. This study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 checklist and quality was assessed via the Newcastle-Ottawa Quality Assessment Scale (NOS). Fourteen observational studies (840 patients) were included in the analysis. 58% of HNAD patients were male (95% CI: 45.2-69.7). Overall prevalence of Malassezia-specific IgE among HNAD patients was 79.3% (95% CI: 57.5-91.5). Prevalence of Malassezia-specific IgE among HNAD patients varied significantly between geographical regions (p = 0.0441), with 88% in non-Asian regions (95% CI: 61.06-97.17) and 54.73% in Asian regions (95% CI: 34.36-73.63). Malassezia-specific IgE prevalence among HNAD patients varied significantly among studies of higher and lower NOS quality score (p = 0.0386), with 95.42% in studies with NOS ≥7 (95% CI: 63.54-99.60) and 58.05% in studies with NOS <7 (95% CI: 41.44-73.01). Malassezia-specific IgE prevalence among HNAD patients did not vary significantly between more and less predominant Malassezia species (p = 0.1048). Malassezia spp. plays a crucial role in the pathogenesis of HNAD, and IgE anti-Malassezia antibodies appeared to be a common marker for HNAD. Understanding the pathophysiology of Malassezia in HNAD can help develop more targeted therapeutic approaches in managing AD.


Assuntos
Dermatite Atópica , Imunoglobulina E , Malassezia , Malassezia/imunologia , Humanos , Imunoglobulina E/sangue , Dermatite Atópica/microbiologia , Dermatite Atópica/imunologia , Prevalência , Eczema/imunologia , Eczema/microbiologia , Masculino , Pescoço/microbiologia , Feminino , Cabeça/microbiologia
2.
Int J Biol Macromol ; 270(Pt 2): 132408, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754683

RESUMO

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.


Assuntos
Alcaloides , Antivirais , Apoptose , Sistema de Sinalização das MAP Quinases , Matrinas , Vírus da Diarreia Epidêmica Suína , Quinolizinas , Glicoproteína da Espícula de Coronavírus , Quinolizinas/farmacologia , Quinolizinas/química , Alcaloides/farmacologia , Alcaloides/química , Animais , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Antivirais/farmacologia , Antivirais/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Chlorocebus aethiops , Células Vero , Suínos , Replicação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
3.
Adv Simul (Lond) ; 9(1): 20, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38750552

RESUMO

BACKGROUND: Themes of equity, diversity and inclusion (EDI) arise commonly within healthcare simulation. Though faculty development guidance and standards include increasing reference to EDI, information on how faculty might develop in this area is lacking. With increasingly formal expectations being placed on simulation educators to adhere to EDI principles, we require a better understanding of the developmental needs of educators and clear guidance so that teams can work towards these expectations. Our study had two aims: Firstly, to explore the extent to which an existing competency framework for medical teachers to teach ethnic and cultural diversity is relevant for simulation educator competency in EDI, and secondly, informed by the data gathered, to construct a modified competency framework in EDI for simulation educators. METHODS: We engaged our participants (10 simulation faculty) in a 5-month period of enhanced consideration of EDI, using the SIM-EDI tool to support faculty debriefing conversations focussed on EDI within a pre-existing programme of simulation. We interviewed participants individually at two timepoints and analysed transcript data using template analysis. We employed an existing competency framework for medical teachers as the initial coding framework. Competencies were amended for the simulation context, modified based on the data, and new themes were added inductively, to develop a new developmental framework for simulation educators. RESULTS: Interview data supported the relevance of the existing competency framework to simulation. Modifications made to the framework included the incorporation of two inductively coded themes ('team reflection on EDI' and 'collaboration'), as well as more minor amendments to better suit the healthcare simulation context. The resultant Developmental Framework for Simulation Educators in EDI outlines 10 developmental areas we feel are required to incorporate consideration of EDI into simulation programmes during the design, delivery and debriefing phases. We propose that the framework acts as a basis for simulation faculty development in EDI. CONCLUSIONS: Simulation faculty development in EDI is important and increasingly called for by advisory bodies. We present a Developmental Framework for Simulation Educators in EDI informed by qualitative data. We encourage simulation teams to incorporate this framework into faculty development programmes and report on their experiences.

4.
Plant Mol Biol ; 114(3): 37, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602592

RESUMO

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.


Assuntos
Nitratos , Setaria (Planta) , Espécies Reativas de Oxigênio , Nitratos/farmacologia , Setaria (Planta)/genética , Peróxido de Hidrogênio , Cloreto de Sódio , Oxigênio , Transdução de Sinais , Perfilação da Expressão Gênica , Nitrogênio
5.
J Aerosol Med Pulm Drug Deliv ; 37(2): 100-110, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38640446

RESUMO

Inhalation of liposomes formulated with phospholipids similar to endogenous lung surfactants and lipids offers biocompatibility and versatility within the pulmonary medicine field to treat a range of diseases such as lung cancer, cystic fibrosis and lung infections. Manipulation of the physicochemical properties of liposomes enables innovative design of the carrier to meet specific delivery, release and targeting requirements. This delivery system offers several benefits: improved pharmacokinetics with reduced toxicity, enhanced therapeutic efficacy, increased delivery of poorly soluble drugs, taste masking, biopharmaceutics degradation protection and targeted cellular therapy. This section provides an overview of liposomal formulation and delivery, together with their applications for different disease states in the lung.


Assuntos
Lipossomos , Pneumonia , Humanos , Lipossomos/química , Lipossomos/metabolismo , Administração por Inalação , Pulmão/metabolismo , Fosfolipídeos , Sistemas de Liberação de Medicamentos
6.
Heliyon ; 10(7): e28325, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571655

RESUMO

Background: Periodontal disease and coronary heart disease are both prevalent diseases worldwide and cause patients physical and mental suffering and a global burden. Recent studies have suggested a link between periodontal disease and coronary heart disease, but there is less research in this field from the perspective of bibliometrics. Objective: This study aimed to quantitatively analyze the literature on periodontal disease and coronary heart disease to summarize intellectual bases, research hotspots, and emerging trends and pave the way for future research. Methods: The Science Citation Index Expanded database was used to retrieve study records on periodontal disease and coronary heart disease from 1993 to 2022. After manual screening, the data were used for cooperative network analysis (including countries/regions, institutions and authors), keyword analysis, and reference co-citation analysis by CiteSpace software. Microsoft Excel 2019 was applied for curve fitting of annual trend in publications and citations. Results: A total of 580 studies were included in the analysis. The number of publications and citations in this field has shown an upward trend over the past 30 years. There was less direct collaboration among authors and institutions in this field but closer collaboration between countries. The United States was the country with the most published articles in this field (169/580, 29.14%). Based on the results of keyword analysis and literature co-citation analysis, C-reactive protein, oral flora, atherosclerosis, infection, and inflammation were previous research hotspots, while global burden and cardiovascular outcomes were considered emerging trends in this field. Conclusion: Studies on periodontal disease and coronary heart disease, which have attracted the attention of an increasing number of researchers, have been successfully analyzed using bibliometrics and visualization techniques. This paper will help scholars better understand the dynamic evolution of periodontal disease and coronary heart disease and point out the direction for future research. Clinical significance: This paper presents an overview between periodontal disease and coronary heart disease. Further exploration of the two diseases themselves and the potential causal relationship between the two is necessary and relevant, which may impact basic research, diagnosis, and treatment related to both diseases. This will aid the work of researchers and specialist doctors, and ultimately benefit patients with both diseases.

7.
Int J Pharm ; 655: 124009, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38493838

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/farmacologia , COVID-19/prevenção & controle , Preparações Farmacêuticas , Pós
8.
J Affect Disord ; 355: 231-238, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38548199

RESUMO

BACKGROUND: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age-comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies. METHODS: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g-score, harmonized across studies), and within OABD between g-score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning. RESULTS: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g-score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g-scores were associated with fewer manic symptoms, higher education and better functioning. LIMITATIONS: Cross-sectional design and loss of granularity due to harmonization. CONCLUSION: More research is needed to understand heterogenous longitudinal patterns of cognitive change in BD and understand whether particular cognitive domains might be affected in OABD in order to develop new therapeutic efforts for cognitive dysfunction OABD.


Assuntos
Transtorno Bipolar , Disfunção Cognitiva , Humanos , Idoso , Transtorno Bipolar/psicologia , Estudos Transversais , Cognição , Envelhecimento/psicologia , Disfunção Cognitiva/complicações , Testes Neuropsicológicos
9.
Drug Deliv Transl Res ; 14(7): 1776-1793, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38441832

RESUMO

This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aß clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In this context, the evaluation of administration devices for nose-to-brain drug delivery becomes crucial in ensuring precise drug deposition patterns and enhancing bioavailability.


Assuntos
Administração Intranasal , Doença de Alzheimer , Encéfalo , Insulina , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Insulina/administração & dosagem , Insulina/farmacocinética , Insulina/uso terapêutico , Animais , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Mucosa Nasal/metabolismo
10.
PLoS Pathog ; 20(3): e1012130, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38551978

RESUMO

Classical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In our study, we elucidate the molecular mechanism through which CSFV exploits m6A modifications to circumvent host immune surveillance, thus facilitating its proliferation. We initially discovered that m6A modifications were elevated both in vivo and in vitro upon CSFV infection, particularly noting an increase in the expression of the methyltransferase METTL14. CSFV non-structural protein 5B was found to hijack HRD1, the E3 ubiquitin ligase for METTL14, preventing METTL14 degradation. MeRIP-seq analysis further revealed that METTL14 specifically targeted and methylated TLRs, notably TLR4. METTL14-mediated regulation of TLR4 degradation, facilitated by YTHDF2, led to the accelerated mRNA decay of TLR4. Consequently, TLR4-mediated NF-κB signaling, a crucial component of the innate immune response, is suppressed by CSFV. Collectively, these data effectively highlight the viral evasion tactics, shedding light on potential antiviral strategies targeting METTL14 to curb CSFV infection.


Assuntos
Adenina , Vírus da Febre Suína Clássica , Peste Suína Clássica , Animais , Vírus da Febre Suína Clássica/genética , Imunidade Inata , Suínos , Receptor 4 Toll-Like
11.
Psychiatry Res ; 333: 115760, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301285

RESUMO

The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older adults (≥ 65) using data from the English Longitudinal Study of Ageing (ELSA) and further investigated the causal association in Mendelian randomization (MR) analysis. In total of 7,223 individuals, 5.7 % developed dementia (1.7 % Alzheimer's disease (AD)) within an average of 8 (± 2.9) years. Cox regression models and MR were employed. Long sleep duration (>8 h) was associated with 64 % increased risk of incident dementia and 2-fold high risk of AD compared to ideal sleep duration (7-8 h). This association was particularly evident in older-older adults (≥70 years) and those who consumed alcohol. Short sleep duration (<7 h) was associated with lower risk of incident dementia among older-older but higher risk among younger-older adults. Sleep disturbances and perceived sleep quality were not associated with dementia or AD. The MR study did not reveal causal associations between sleep duration and dementia. These findings suggest that self-reported short sleep in younger-older and long sleep in older-older adults and those with frequent alcohol consumption are associated with dementia. Early detection of these sleep patterns may help identify individuals at higher dementia risk.


Assuntos
Doença de Alzheimer , Transtornos do Sono-Vigília , Humanos , Idoso , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/complicações , Seguimentos , Estudos Longitudinais , Duração do Sono , Incidência , Sono , Transtornos do Sono-Vigília/complicações
12.
Mol Neurobiol ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418757

RESUMO

Stroke stands as the second leading cause of death globally, surpassed only by ischemic heart disease. It accounts for 9% of total worldwide deaths. Given the swiftly evolving landscape, medical professionals and researchers are devoting increased attention to identifying more effective and safer treatments. Recent years have witnessed a focus on exosomes derived from mesenchymal stem cells cultivated under hypoxic conditions, referred to as Hypo-Exo. These specialized exosomes contain an abundance of components that facilitate the restoration of ischemic tissue, surpassing the content found in normal exosomes. Despite advancements, the precise role of Hypo-Exo in cases of cerebral ischemia remains enigmatic. Therefore, this study was designed to shed light on the potential efficacy of Hypo-Exo in stroke treatment. Our investigations unveiled promising outcomes, as the administration of Hypo-Exo led to improved behavioral deficits and reduced infarct areas in mice affected by ischemic conditions. Notably, these positive effects were hindered when Hypo-Exo loaded with anti-miR-214-3p were introduced, implying that the neuroprotective attributes of Hypo-Exo are reliant on miR-214-3p. This conclusion was substantiated by the high levels of miR-214-3p detected within Hypo-Exo. Furthermore, our examination of the ischemic penumbra zone revealed a gradual and sustained escalation in PTEN expression, a phenomenon effectively countered by Hypo-Exo treatment. Collectively, our findings suggest the existence of a regulatory pathway centered on miR-214-3p within Hypo-Exo. This pathway exerts a downregulating influence on the PTEN/Akt signaling pathway, thereby contributing to the amelioration of neurological function subsequent to ischemia-reperfusion events.

13.
J Nutr Health Aging ; 28(3): 100169, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308922

RESUMO

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.


Assuntos
Desnutrição , Estado Nutricional , Humanos , Pacientes Internados , Apoio Nutricional , Desnutrição/epidemiologia , Desnutrição/prevenção & controle , China , Avaliação Nutricional
14.
Front Immunol ; 15: 1336498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322263

RESUMO

Background: Despite the recognized link between immune responses and frailty, the association between immune cell counts and frailty based on previous observational studies remains disputed, with uncertain causal nexus. This study aimed to elucidate causal association between genetically predicted circulating immune cell counts and frailty. Methods: We conducted the two-sample Mendelian randomization (MR) study with independent genetic variants associated with six immune cell subtype counts from genome-wide association studies in 563,946 European individuals. Frailty summary data, assessed via frailty index (FI), was obtained from study comprising 175,226 subjects. Univariate MR, reverse MR and multivariate MR were conducted to comprehensive investigate the association between immune cell counts and FI, with two-step MR analysis for mediation analysis. Results: Univariate MR evidence indicated that among six leukocyte subtype counts, only elevated eosinophil count was significantly correlated with higher FI (ß = 0.059, 95% confidence interval [CI], 0.042-0.078, P=5.63E-11), with no reverse causal relationship identified in reverse MR. In multivariate MR, the causal effect of eosinophil count retained statistical significance (ß = 0.063, 95% CI, 0.021-0.104, P = 0.003). Ultimately, the two-step MR analysis demonstrated two mediators in this causal pathway: asthma (ß= 0.019, 95% CI, 0.013-0.025, P = 35.84E-10, mediated proportion, 31.732%) and rheumatoid arthritis (ß= 0.004, 95% CI, 0.001-0.006, P=1.75E-03, mediated proportion, 6.411%). Conclusions: Within immune cell subtypes, MR evidence indicated only genetically predicted circulating eosinophil count had irreversible and independent causal effect on frailty, with asthma and rheumatoid arthritis possibly serving as partial mediators. The finding stressed the need for further exploring physiological functions of eosinophils in order to develop effective strategies against frailty.


Assuntos
Artrite Reumatoide , Asma , Fragilidade , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Contagem de Leucócitos
15.
Int J Pharm ; 654: 123922, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38401871

RESUMO

The surge in neurological disorders necessitates innovative strategies for delivering active pharmaceutical ingredients to the brain. The non-invasive intranasal route has emerged as a promising approach to optimize drug delivery to the central nervous system by circumventing the blood-brain barrier. While the intranasal approach offers numerous advantages, the lack of a standardized protocol for drug testing poses challenges to both in vitro and in vivo studies, limiting the accurate interpretation of nasal drug delivery and pharmacokinetic data. This review explores the in vitro experimental assays employed by the pharmaceutical industry to test intranasal formulation. The focus lies on understanding the diverse techniques used to characterize the intranasal delivery of drugs targeting the brain. Parameters such as drug release, droplet size measurement, plume geometry, deposition in the nasal cavity, aerodynamic performance and mucoadhesiveness are scrutinized for their role in evaluating the performance of nasal drug products. The review further discusses the methodology for in vivo characterization in detail, which is essential in evaluating and refining drug efficacy through the nose-to-brain pathway. Animal models are indispensable for pre-clinical drug testing, offering valuable insights into absorption efficacy and potential variables affecting formulation safety. The insights presented aim to guide future research in intranasal drug delivery for neurological disorders, ensuring more accurate predictions of therapeutic efficacy in clinical contexts.


Assuntos
Encéfalo , Doenças do Sistema Nervoso , Animais , Administração Intranasal , Encéfalo/metabolismo , Nariz , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas/química , Proteínas/metabolismo , Peptídeos/metabolismo , Mucosa Nasal/metabolismo
16.
Psych J ; 13(3): 486-493, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38298152

RESUMO

Theory of mind (ToM) and empathy are considered key components of social cognition that are often impaired in individuals with autism spectrum disorders (ASD). However, it remains unclear whether individuals with high levels of autistic traits exhibit similar impairments in these two functions. This study examined the affective and cognitive domains of ToM and empathy in individuals with high levels of autistic traits. We recruited 84 participants with high levels and 78 participants with low levels of autistic traits to complete a set of self-reported checklists and performance-based tasks capturing affective and cognitive components of ToM and empathy. The results showed that participants with high levels of autistic traits exhibited significant impairments in cognitive but not in affective ToM and empathy compared with their counterparts with low levels of autistic traits. We also found that empathy impairments in people with high levels of autistic traits were confounded by alexithymia and depressive traits.


Assuntos
Transtorno do Espectro Autista , Empatia , Teoria da Mente , Humanos , Masculino , Feminino , Transtorno do Espectro Autista/psicologia , Adulto , Cognição/fisiologia , Adulto Jovem , Sintomas Afetivos , Transtorno Autístico/psicologia
17.
J Hepatol ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423478

RESUMO

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC. METHODS: We combined single-cell transcriptomics (single-cell RNA sequencing) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs. FC. RESULTS: We found that the intrahepatic environment in CHB and FC displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with the emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes, and an activated innate response represented by liver-resident natural killer cells, specific Kupffer cell subtypes and marginated neutrophils. Surprisingly, we found MHC class II-expressing hepatocytes in patients achieving FC, as well as low but persistent levels of covalently closed circular DNA and pregenomic RNA, which may play an important role in FC. CONCLUSIONS: Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic development. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis. IMPACT AND IMPLICATIONS: This study dissects the immuno-pathological cell states associated with functionally cured chronic hepatitis B (defined by the loss of HBV surface antigen or HBsAg). We identified the sustained presence of very low viral load, accessory antigen-presenting hepatocytes, adaptive-memory-like natural killer cells, and the emergence of helper CD4 T cells with cytotoxic or effector-like signatures associated with functional cure, suggesting previously unsuspected alterations in the adaptive immune response, as well as a key role for the innate immune response in achieving or maintaining functional cure. Overall, the insights generated from this study may provide new avenues for the development of alternative therapies as well as patient surveillance for better clinical management of chronic hepatitis B.

18.
Lab Chip ; 24(6): 1676-1684, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38305095

RESUMO

Ultrasonic atomization of liquids into micrometer-diameter droplets is crucial across multiple fields, ranging from drug delivery, to spectrometry and printing. Controlling the size and uniformity of the generated droplets on-demand is crucial in all these applications. However, existing systems lack the required precision to tune the droplet properties, and the underlying droplet formation mechanism under high-frequency ultrasonic actuation remains poorly understood due to experimental constraints. Here, we present an atomization platform, which overcomes these current limitations. Our device utilizes oscillating high aspect ratio micro-channels to extract liquids from various inlets (ranging from sessile droplets to large beakers), bound them in a precisely defined narrow region, and, controllably atomize them on-demand. The droplet size can be precisely dialled from 3.6 µm to 6.8 µm by simply tuning the actuation parameters. Since the approach does not need nozzles, meshes or impacting jets, stresses exerted on the liquid samples are reduced, hence it is gentler on delicate samples. The precision offered by the technique allows us for the first time to experimentally visualise the oscillating fluid interface at the onset of atomization at MHz frequencies, and demonstrate its applications for targeted respiratory drug delivery.

19.
World J Clin Cases ; 12(1): 157-162, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38292637

RESUMO

BACKGROUND: Glucose imbalance is common in total parenteral nutrition (TPN). Hypoglycemia seems to be less frequent than hyperglycemia, but it influences the clinical outcome to a greater extent. Therefore, it should be effectively prevented and treated. However, there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury. CASE SUMMARY: We present three patients with liver cell injury who developed severe hypoglycemia during or after TPN infusion. The causes of severe hypoglycemia and glucose-raising strategies were discussed. According to the physiological characteristics of the hepatocellular injury, the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases. We simultaneously reduced the dose of insulin and fat emulsion, and increased the dose of glucose in TPN. The blood glucose level was restored to normal range and clinical symptoms were eliminated. CONCLUSION: When hypoglycemia occurs during or after TPN in patients with hepatocellular injury, physicians need to simultaneously reduce insulin and fat emulsion, and increase glucose, and correct severe hypoglycemia in time to reduce its adverse consequences.

20.
Respirol Case Rep ; 12(1): e01278, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38239333

RESUMO

Inflammatory endobronchial polyps (IEPs) are rare benign lesions that originate from the bronchial mucosa. While pneumothorax is a well-known complication of various pulmonary conditions, its association with IEPs is exceedingly uncommon and poorly understood. This case report presents a unique and explosive encounter of a patient with an inflammatory endobronchial polyp who experienced a pneumothorax, shedding light on the clinical presentation, diagnostic challenges, and management strategies for this rare entity.

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