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1.
Lung ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641747

RESUMO

PURPOSE: The response to glucocorticoids is hampered in many COPD patients by a yet unknown mechanism. Earlier we reported that short-term heat exposure of primary human bronchial epithelial cells (BEC) and airway smooth muscle cells (ASMC) of asthma patients increased the expression and secretion of extracellular heat shock proteins (eHSPs) resulting in increased expression of glucocorticoid receptor (GR) in BEC and inhibition of ASMC remodeling. The aim of the present study was to assess if the same mechanism is also present in primary airway wall cells of COPD patients. METHODS: Primary BEC and ASMC were established from endobronchial biopsies obtained from COPD patients (n = 73), who participated in the HISTORIC study, an investigator-initiated and driven clinical trial. Secretion and protein expression of HSPs was assessed by ELISA and Western blotting. Expression of total GR, its isoforms GRα and GRß and toll-like receptor 4 (TLR4) was determined by Western-blotting. RESULTS: Short heat exposure (65 °C, 10 s) of BEC resulted in a significant increase of the secretion of eHSP70 and eHSP90, while the intracellular protein was not altered. Heat treatment or exposure to eHSP70 or eHSP90 had no effect on the expression of GR and GR-isoforms. However, eHSP70 and eHSP90 significantly reduced the expression of TLR4. CONCLUSIONS: The results of this study indicate that primary airway cells from COPD patients respond differently to heat exposure and extracellular HSP70 or HSP90 than cells from asthma patients regarding the expression of GR and this may explain the reduced response to glucocorticoids in patients with COPD. TRIAL REGISTRATION: ISRCTN11017699.

2.
Brief Funct Genomics ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605526

RESUMO

Intermolecular interactions of protein-protein complexes play a principal role in the process of discovering new substances used in the diagnosis and treatment of many diseases. Among such complexes of proteins, we have to mention antibodies; they interact with specific antigens of two genera of single-stranded RNA viruses belonging to the family Filoviridae-Ebolavirus and Marburgvirus; both cause rare but fatal viral hemorrhagic fever in Africa, with pandemic potential. In this research, we conduct studies aimed at the design and evaluation of antibodies targeting the filovirus glycoprotein precursor GP-1,2 to develop potential targets for the pan-filovirus easy-to-use rapid diagnostic tests. The in silico research using the available 3D structure of the natural antibody-antigen complex was carried out to determine the stability of individual protein segments in the process of its formation and maintenance. The computed free binding energy of the complex and its decomposition for all amino acids allowed us to define the residues that play an essential role in the structure and indicated the spots where potential antibodies can be improved. Following that, the study involved targeting six epitopes of the filovirus GP1,2 with two polyclonal antibodies (pABs) and 14 monoclonal antibodies (mABs). The evaluation conducted using Enzyme Immunoassays tested 62 different sandwich combinations of monoclonal antibodies (mAbs), identifying 10 combinations that successfully captured the recombinant GP1,2 (rGP). Among these combinations, the sandwich option (3G2G12* - (rGP) - 2D8F11) exhibited the highest propensity for capturing the rGP antigen.

3.
J Pers Med ; 14(3)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38540990

RESUMO

In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management.

4.
Cancers (Basel) ; 16(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38339329

RESUMO

BACKGROUND: Teledermatology is employed in the diagnosis and follow-up of skin cancer and its use was intensified during and after the COVID-19 pandemic. At the same time, demographic changes result in an overall increase in non-melanoma skin cancer and skin precancerous lesions. The aim of this study was to elucidate the role of teledermatology in comparison to conventional face-to-face dermatology for such lesions and determine the advantages and limitations of this workflow for patients and physicians. METHODS: Research was performed using relevant keywords in MEDLINE and CENTRAL. Relevant articles were chosen following a predetermined standardized extraction form. RESULTS: Diagnostic accuracy and interrater/intrarater agreement can be considered comparable-although lower-than in-person consultation. Improvement of particular features such as image quality, medical history availability, and teledermoscopy can further increase accuracy. Further aspects of limitations and advantages (mean time-to-assessment, time-to-treatment, cost-effectiveness) are discussed. CONCLUSIONS: Teledermatology has comparable diagnostic accuracy with face-to-face dermatology and can be utilized both for the effective triage of non-melanocytic epithelial tumors and precancerous lesions, as well as the follow-up. Easy access to dermatologic consultation with shorter mean times to diagnostic biopsy and/or treatment coupled with cost-effectiveness could compensate for the lower sensitivity of teledermatology and offer easier access to medical care to the affected populations.

5.
Am J Physiol Cell Physiol ; 326(3): C850-C865, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38145300

RESUMO

Wnt1-inducible signaling protein 1 (WISP1/CCN4) is a secreted matricellular protein that is implicated in lung and airway remodeling. The macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been associated with chronic lung diseases. In this study, we aimed to investigate the WISP1 signaling pathway and its ability to induce the expression of MIF in primary cultures of fibroblasts from normal human lungs (HLFs). Our results showed that WISP1 significantly stimulated the expression of MIF in a concentration- and time-dependent fashion. In WISP1-induced expression of MIF, αvß5-integrin and chondroitin sulfate proteoglycans as well as Src tyrosine kinases, MAP kinases, phosphatidylinositol 3-kinase/Akt, PKC, and NF-κB were involved. WISP1-induced expression of MIF was attenuated in the presence of the Src kinase inhibitor PP2 or the MIF tautomerase activity inhibitor ISO-1. Moreover, WISP1 significantly increased the phosphorylation and activation of EGF receptor (EGFR) through transactivation by Src kinases. WISP1 also induced the expression of MIF receptor CD74 and coreceptor CD44, through which MIF exerts its effects on HLFs. In addition, it was found that MIF induced its own expression, as well as its receptors CD74/CD44, acting in an autocrine manner. Finally, WISP1-induced MIF promoted the expression of cyclooxygenase 2, prostaglandin E2, IL-6, and matrix metalloproteinase-2 demonstrating the regulatory role of WISP1-MIF axis in lung inflammation and remodeling involving mainly integrin αvß5, Src kinases, PKC, NF-κB, and EGFR. The specific signaling pathways involved in WISP1-induced expression of MIF may prove to be excellent candidates for novel targets to control inflammation in chronic lung diseases.NEW & NOTEWORTHY The present study demonstrates for the first time that Wnt1-inducible signaling protein 1 (WISP1) regulates migration inhibitory factor (MIF) expression and activity and identifies the main signaling pathways involved. The newly discovered WISP1-MIF axis may drive lung inflammation and could result in the design of novel targeted therapies in inflammatory lung diseases.


Assuntos
Pneumopatias , Fatores Inibidores da Migração de Macrófagos , Pneumonia , Humanos , Receptores ErbB , Pulmão , Fatores Inibidores da Migração de Macrófagos/genética , Metaloproteinase 2 da Matriz , NF-kappa B , Transdução de Sinais , Quinases da Família src
6.
Respir Res ; 24(1): 225, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740199

RESUMO

Sensitization to Staphylococcus aureus enterotoxins A (SEA) and B (SEB) has been associated with asthma severity, exacerbations, and disease control. Our study aimed to investigate if there are differences in serum SEA-IgE and SEB-IgE levels between patients with chronic obstructive pulmonary disease (COPD), asthma, and controls, and to assess the association between SE sensitization and COPD clinical parameters and Th2 inflammation biomarkers in two well-defined COPD cohorts. Our findings suggest that COPD patients do not exhibit higher SEA and SEB sensitization compared to asthma patients and controls. However, in COPD patients, the presence of atopy and allergy is associated with positivity for SEA-IgE and SEB-IgE. Consequently, these allergens may aid in identifying atopic or allergic subgroups within the COPD population, but they are not directly associated with the diagnosis of COPD, elevated circulating blood eosinophils, or fractional exhaled nitric oxide (FENO) levels.


Assuntos
Asma , Hipersensibilidade Imediata , Hipersensibilidade , Doença Pulmonar Obstrutiva Crônica , Humanos , Staphylococcus aureus , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Enterotoxinas , Imunoglobulina E
7.
Adv Exp Med Biol ; 1423: 41-57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525032

RESUMO

TANK-binding kinase 1 protein (TBK1) is a kinase that belongs to the IκB (IKK) family. TBK1, also known as T2K, FTDALS4, NAK, IIAE8, and NF-κB, is responsible for the phosphorylation of the amino acid residues, serine and threonine. This enzyme is involved in various key biological processes, including interferon activation and production, homeostasis, cell growth, autophagy, insulin production, and the regulation of TNF-α, IFN-ß, and IL-6. Mutations in the TBK1 gene alter the protein's normal function and may lead to an array of pathological conditions, including disorders of the central nervous system. The present study sought to elucidate the role of the TBK1 protein in amyotrophic lateral sclerosis (ALS), a human neurodegenerative disorder. A broad evolutionary and phylogenetic analysis of TBK1 was performed across numerous organisms to distinguish conserved regions important for the protein's function. Subsequently, mutations and SNPs were explored, and their potential effect on the enzyme's function was investigated. These analytical steps, in combination with the study of the secondary, tertiary, and quaternary structure of TBK1, enabled the identification of conserved motifs, which can function as novel pharmacological targets and inform therapeutic strategies for amyotrophic lateral sclerosis.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Humanos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Filogenia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/genética , Fosforilação , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
8.
Adv Exp Med Biol ; 1423: 59-78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525033

RESUMO

SARS-CoV-2 is a coronavirus responsible for one of the most serious, modern worldwide pandemics, with lasting and multifaceted effects. By late 2021, SARS-CoV-2 has infected more than 180 million people and has killed more than 3 million. The virus gains entrance to human cells through binding to ACE2 via its surface spike protein and causes a complex disease of the respiratory system, termed COVID-19. Vaccination efforts are being made to hinder the viral spread, and therapeutics are currently under development. Toward this goal, scientific attention is shifting toward variants and SNPs that affect factors of the disease such as susceptibility and severity. This genomic grammar, tightly related to the dark part of our genome, can be explored through the use of modern methods such as natural language processing. We present a semantic analysis of SARS-CoV-2-related publications, which yielded a repertoire of SNPs, genes, and disease ontologies. Population data from the 1000 Genomes Project were subsequently integrated into the pipeline. Data mining approaches of this scale have the potential to elucidate the complex interaction between COVID-19 pathogenesis and host genetic variation; the resulting knowledge can facilitate the management of high-risk groups and aid the efforts toward precision medicine.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Semântica , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único
9.
Adv Exp Med Biol ; 1423: 79-99, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525034

RESUMO

Mental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder, and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists, and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family toward drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, the structural comparison of ADRA2B, HTR1A, and other members of GPCRs related to mental disorders is performed.


Assuntos
Transtornos Mentais , Receptor 5-HT1A de Serotonina , Receptores de Amina Biogênica , Humanos , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Receptor 5-HT1A de Serotonina/genética , Receptores Adrenérgicos alfa 2 , Receptores de Amina Biogênica/genética , Receptores de Amina Biogênica/metabolismo , Serotonina , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Ideação Suicida
10.
Adv Exp Med Biol ; 1423: 101-113, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525035

RESUMO

All living organisms have been programmed to maintain a complex inner equilibrium called homeostasis, despite numerous adversities during their lifespan. Any threatening or perceived as such stimuli for homeostasis is termed a stressor, and a highly conserved response system called the stress response system has been developed to cope with these stimuli and maintain or reinstate homeostasis. The glucocorticoid receptor, a transcription factor belonging to the nuclear receptors protein superfamily, has a major role in the stress response system, and research on its interactome may provide novel information regarding the mechanisms underlying homeostasis maintenance. A list of 149 autosomal genes that have an essential role in GR function or are prime examples of GRE-containing genes was composed in order to gain a comprehensive view of the GR interactome. A search for SNPs on those particular genes was conducted on a dataset of 3554 Japanese individuals, with mentioned polymorphisms being annotated with relevant information from the ClinVar, LitVar, and dbSNP databases. Forty-two SNPs of interest and their genomic locations were identified. These SNPs have been associated with drug metabolism and neuropsychiatric, metabolic, and immune system disorders, while most of them were located in intronic regions. The frequencies of those SNPs were later compared with a dataset consisting of 1465 Korean individuals in order to find population-specific characteristics based on some of the identified SNPs of interest. The results highlighted.that rs1043618 frequencies were different in the two populations, with mentioned polymorphism having a potential role in chronic obstructive pulmonary disease in response to environmental stressors. This SNP is located in the HSPA1A gene, which codes for an essential GR co-chaperone, and such information showcases that similar gene may be novel genomic targets for managing or combatting stress-related pathologies.


Assuntos
População do Leste Asiático , Receptores de Glucocorticoides , Humanos , Genômica , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
11.
Adv Exp Med Biol ; 1423: 235-236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525049

RESUMO

Breast milk is the ideal food for the premature and mature babies and has undoubtedly immediate and ultimate benefits. Among other things, it protects against infections, reduces the risk of necrotizing enterocolitis and retinopathy of the premature babies, improves neurodevelopmental outcome, and reduces the risk of obesity and metabolic syndrome later in life. In the present study, breast milk will be studied with all the available omics technologies. More specifically, functional genomics, comparative genomics, transcriptomics, sequencing, proteomics, and metabolomics will be performed. The above results and this multidimensional information will be coordinated under the framework of a holistic approach of systems biology and bioinformatic analysis. Important IncRNAs and protein molecules will be validated as candidate biomarkers in exosomes of a larger group of breast milk and blood/serum samples. Validated ncRNAs/proteins will be analyzed in exudates of breast milk and bovine, goat, and sheep milk to explore new ways to improve milk synthesis. Expression of ncRNAs, unlike mRNAs, is a direct indicator of their functional presence. The information to be generated in this study will be analyzed by mining and data combining techniques and algorithms. After defining breast milk molecular fingerprinting, an attempt will be made to enhance the commercial product. The benefits of breast milk are attributed to its various components, including nutrients, hormones, growth factors, immune cells, antibodies, cytokines, antimicrobial peptides, and extracellular vesicles.


Assuntos
Exossomos , Vesículas Extracelulares , Lactente , Feminino , Ovinos , Recém-Nascido , Humanos , Animais , Bovinos , Leite Humano/química , Leite , Recém-Nascido Prematuro , Exossomos/genética , Exossomos/metabolismo , Genômica
12.
Adv Exp Med Biol ; 1423: 245-250, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37525051

RESUMO

Exploring the origin of plastids is an interesting theme for study because it enhances our knowledge of the basis of photosynthesis in flora. Plastids, which are organelles, are actually the major sites of photosynthesis in eukaryotic cells. Plastids are also every chloroplast which contains cytoplasmic organelles, enabling the harvesting and conversion of light and carbon dioxide into food and energy. Plastids can be found in eukaryotic cells, and according to their structure in their membrane, they can be separated in primary (which can be found in most algae and plants) and secondary plastids (which can be found in plankton).


Assuntos
Eixo Encéfalo-Intestino , Simbiose , Plantas , Plastídeos/metabolismo , Fotossíntese , Filogenia , Evolução Biológica
13.
Adv Exp Med Biol ; 1424: 97-115, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37486484

RESUMO

Cognitive and behavioral disorders are subgroups of mental health disorders. Both cognitive and behavioral disorders can occur in people of different ages, genders, and social backgrounds, and they can cause serious physical, mental, or social problems. The risk factors for these diseases are numerous, with a range from genetic and epigenetic factors to physical factors. In most cases, the appearance of such a disorder in an individual is a combination of his genetic profile and environmental stimuli. To date, researchers have not been able to identify the specific causes of these disorders, and as such, there is urgent need for innovative study approaches. The aim of the present study was to identify the genetic factors which seem to be more directly responsible for the occurrence of a cognitive and/or behavioral disorder. More specifically, through bioinformatics tools and software as well as analytical methods such as systemic data and text mining, semantic analysis, and scoring functions, we extracted the most relevant single nucleotide polymorphisms (SNPs) and genes connected to these disorders. All the extracted SNPs were filtered, annotated, classified, and evaluated in order to create the "genomic grammar" of these diseases. The identified SNPs guided the search for top suspected genetic factors, dopamine receptors D and neurotrophic factor BDNF, for which regulatory networks were built. The identification of the "genomic grammar" and underlying factors connected to cognitive and behavioral disorders can aid in the successful disease profiling and the establishment of novel pharmacological targets and provide the basis for personalized medicine, which takes into account the patient's genetic background as well as epigenetic factors.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Transtornos Mentais , Humanos , Feminino , Masculino , Fator Neurotrófico Derivado do Encéfalo/genética , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Biologia Computacional , Polimorfismo de Nucleotídeo Único , Cognição
14.
Adv Exp Med Biol ; 1424: 125-133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37486486

RESUMO

Matchmaking has a great position in the rational allocation of resources in several fields, ranging from market operation to people's daily lives. Matchmakers have evolved through artificial intelligence technologies and are being introduced in numerous aspects of industry, research, and academia in solving decision issues, research innovation design, and building robust and efficient networks. The goal of this report is to describe the collaborative platforms and matchmaking algorithms for research and education, as well as the establishment and optimization of consortia.


Assuntos
Algoritmos , Inteligência Artificial , Humanos , Tecnologia
15.
Adv Exp Med Biol ; 1424: 231, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37486498

RESUMO

Modern anticancer research has employed advanced computational techniques and artificial intelligence methods for drug discovery and development, along with the massive amount of generated clinical and in silico data over the last decades. Diverse computational techniques and state-of-the-art algorithms are being developed to enhance traditional Rational Drug Design pipelines and achieve cost-efficient and successful anticancer candidates to promote human health. Towards this direction, we have developed a pharmacophore- based drug design approach against MCT4, a member of the monocarboxylate transporter family (MCT), which is the main carrier of lactate across the membrane and highly involved in cancer cell metabolism. Specifically, MCT4 is a promising target for therapeutic strategies as it overexpresses in glycolytic tumors, and its inhibition has shown promising anticancer effects. Due to the lack of experimentally determined structure, we have elucidated the key features of the protein through an in silico drug design strategy, including for molecular modelling, molecular dynamics, and pharmacophore elucidation, towards the identification of specific inhibitors as a novel anti-cancer strategy.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Proteínas Musculares/metabolismo , Inteligência Artificial , Neoplasias/tratamento farmacológico , Ácido Láctico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Descoberta de Drogas , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo
16.
Breathe (Sheff) ; 19(2): 220267, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37377851

RESUMO

Pharmacological management of airway obstructive diseases is a fast-evolving field. Several advances in unravelling disease mechanisms as well as intracellular and molecular pathways of drug action have been accomplished. While the clinical translation and implementation of in vitro results to the bedside remains challenging, advances in comprehending the mechanisms of respiratory medication are expected to assist clinicians and scientists in identifying meaningful read-outs and designing clinical studies. This European Respiratory Society Research Seminar, held in Naples, Italy, 5-6 May 2022, focused on current and future developments of the drugs used to treat asthma and COPD; on mechanisms of drug action, steroid resistance, comorbidities and drug interactions; on prognostic and therapeutic biomarkers; on developing novel drug targets based on tissue remodelling and regeneration; and on pharmacogenomics and emerging biosimilars. Related European Medicines Agency regulations are also discussed, as well as the seminar's position on the above aspects.

17.
Eur Respir J ; 62(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37385657

RESUMO

BACKGROUND: Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness. METHODS: In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: >20% of the bronchial tissue area) and low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively, and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 µg twice daily). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/placebo and followed for 12 months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1 s (FEV1) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS. RESULTS: In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV1 change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year-1 within the group of patients with LASMC and 183.0 mL·year-1 within the group of patients with HASMC. CONCLUSION: COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Budesonida , Sistema Respiratório , Corticosteroides/uso terapêutico , Administração por Inalação , Músculo Liso , Método Duplo-Cego , Volume Expiratório Forçado
18.
EMBnet J ; 282023.
Artigo em Inglês | MEDLINE | ID: mdl-37378379

RESUMO

Healthy eating has gained ground in people's daily lives in modern society. However, an overwhelming preoccupation with healthy eating can lead to a pathological form setting the ground for orthorexia nervosa. This study aimed to validate the Greek version of the Eating Habits Questionnaire (EHQ) in adults 18 to 65 years old. The EHQ evaluates orthorexia nervosa traits. An online survey was conducted among adults of the general Greek population by administrating a battery of self-report instruments. The IPIP Big-Five personality questionnaire, Beck's Depression Inventory, the Obsessive-Compulsive Inventory-Revised, the Bulimic Investigatory Test, the Edinburg BITE, and the Eating Attitudes Test-13 were used. Internal consistency, test-retest reliability, and convergent and criterion validity were examined. A total of 551 adults (92.2% females) voluntarily participated in the study. Results suggest that the Greek version of the instrument has good psychometric properties. Analysis revealed a 3-factor model explaining 48.20% of the total variance. Cronbach's alphas ranged between 0.80 to 0.82, indicating good internal consistency. The test-retest reliability analysis showed no statistically significant difference between the measurements of the first and the post-2 weeks. Correlations with other eating disorder-related constructs were found to be weak to moderate. Body mass index was not significantly correlated with neither of the three EHQ subscales. The Greek version of EHQ is a robust instrument that could be used in clinical practice and research in the field of eating disorders in Greece.

19.
Respirology ; 28(8): 767-774, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37311657

RESUMO

BACKGROUND AND OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with worsening health outcomes and effective treatment of each episode is essential. In this study, we aimed to investigate if plasma levels of heparan sulphate (HS) are associated with the aetiology of AECOPD. METHODS: COPD patients (N = 1189), GOLD grade II-IV, from a discovery cohort (N = 638) and from a validation cohort (N = 551), were included in the study. HS and heparanase (HSPE-1) were measured longitudinally in plasma at stable state, at AECOPD and at 4 weeks follow-up. RESULTS: Plasma HS was higher in patients with COPD as compared with non-COPD controls and was significantly increased at AECOPD as compared to stable state (p < 0.001) in the discovery and in the validation cohorts. Four distinct exacerbation groups were classified based on aetiology (no-infection/bacterial-infection/viral-infection/bacterial and viral coinfection) in the validation cohort. The fold-increase of HS from stable state to AECOPD was associated with the aetiology of exacerbation and was higher in cases with bacterial and viral coinfections. HSPE-1 was also significantly increased at AECOPD, however, there was no association of HSPE-1 levels with the aetiology of these events. The probability of having an infection at AECOPD was raised as HS levels increased from stable state to AECOPD. This probability was higher for bacterial infections than viral infections. CONCLUSION: The results of our study indicate that circulating levels of HS are increased at AECOPD and this increase may be associated with the aetiology of these events.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Viroses , Humanos , Sulfatos , Progressão da Doença
20.
J Pers Med ; 13(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36836466

RESUMO

Reproductive lifespan is determined by the reserve of ovarian follicles; their quality and quality determine the fertility potential at a given point in time for a particular individual. Inter-individual variations related to morphometry, laterality, medical history, demographic characteristics and ethnicity may impact ovarian histology, which however, has not been extensively studied or documented. The present cross-sectional study aims to investigate the potential association of clinical factors (age, medical and obstetric history) with ovarian morphometry and histology in females of reproductive age in the local population. The sample included 31 specimens of whole human ovaries, obtained from surgical/autopsy procedures in reproductive-aged women, processed at the Pathology Department. Morphometric characteristics were assessed, including shape, color, length, width, thickness and gross ovarian pathology. Random samples of specific dimensions were histologically examined to determine follicular counts. The results were analyzed statistically in correlation to morphometric characteristics and medical history. The majority of the patients had oval-shaped ovaries (77.8% right; 92.3% left; p = 0.368) of whitish color (38.9% right; 46.2% left; p > 0.999). Right ovaries had significantly greater length, width and volume (p-values 0.018, 0.040 and 0.050, respectively). Thickness was equivalent, as well as follicular distribution of all classes. Age correlated inversely with ovarian volume and primordial/primary follicular count on histology. Women with a caesarian-section history yielded significantly lower primordial/primary follicular counts. As estimated by ovarian histology, macroscopic and clinical factors may be significantly associated with actual ovarian reserve.

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