Re-evaluation of the taxonomy of Talaromyces minioluteus

Talaromyces minioluteus belongs to the section Trachyspermi, has a worldwide distribution and has been found on various substrates, especially on various (stored) food commodities and indoor environments. This species is phenotypically and phylogenetically closely related to T. chongqingensis and T. minnesotensis. The phylogenetic and morphological analyses of 37 strains previously identified as T. chongqingensis, T. minnesotensis and T. minioluteus revealed that this clade incudes eight species: the accepted species T. chongqingensis, T. minnesotensis and T. minioluteus, the newly proposed species T. calidominioluteus, T. africanus and T. germanicus, and the new combinations T. gaditanus (basionym Penicillium gaditanum) and T. samsonii (basionym Penicillium samsonii). In this study, we give insight of the phylogenetic relationships and provide detailed descriptions of the species belonging to this clade. Macromorphological features, especially colony growth rates, texture and conidial colors on agar media, are important characters for phenotypic differentiation between species.SUPPLEMENTARY MATERIAL : Figure S1: Maximum Likelihood (ML) tree inferred based on the ITS sequence dataset with GenBank sequences (indicated in red). The BI posterior probabilities and ML bootstrap percentages are presented at the nodes. The fully supported branches are thickened and the BS/PP values are indicated with asterisk. Values less than 70% bs (ML) or less than 0.95 pp (Bayesian analysis) are indicated with a hyphen or not shown. The phylogram is rooted with T. flavus (CBS 310.38T) and T. sayulitensis (CBS 138204). T = ex-type, Table S1: Re-identification of T. minioluteus sequences present in GenBank.https://www.mdpi.com/journal/jofam2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients

Abstract Background Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. Methods In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC 100% - FEF 25–75% Results Treatment with extrafine BDP/FF(200/6 μg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. Conclusions Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 μg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP

Study of new molecular markers with non-invasive methods in respiratory diseases, with particular regard to Idiopathic Pulmonary Fibrosis

Introduzione: La fibrosi polmonare idiopatica (IPF) è una forma di polmonite interstiziale fibrosante ad eziologia sconosciuta, con andamento progressivo, che porta rapidamente alla morte. Poiché la diagnosi di IPF è complessa, la ricerca di nuovi biomarcatori, in particolare di quelli non invasivi è di grande importanza per la gestione di questi pazienti. Lo scopo di questo studio è stato quello di valutare, nell’esalato condensato (EBC) dei pazienti IPF, le alterazioni del DNA mitocondriale (MtDNA), marcatore di stress ossidativo, ed il potenziale ruolo della Periostina e delle alterazioni genetiche dei microsatelliti (MAs) nella patogenesi dell'IPF. Materiali e Metodi: 48 pazienti con diagnosi di IPF sono stati confrontati con 20 soggetti controllo. I pazienti sono stati sottoposti alla raccolta di EBC e di sangue. Il contenuto del DNA mitocondriale (MtDNA) e del DNA nucleare (nDNA) è stato amplificato e quantificato nell’EBC e nel sangue mediante Real Time PCR. Il rapporto tra MtDNA/nDNA è stato poi calcolato. La concentrazione della Periostina è stata valutata nell’EBC mediante test immunoenzimatico (ELISA). Quattro marcatori microsatellitari (THRA1, D17S579, D17S250 e D8S137) sono stati utilizzati per l'analisi delle MAs. Il DNA ottenuto dall'EBC e dal sangue è stato amplificato mediante PCR; i prodotti di PCR sono stati poi analizzati utilizzando un sequenziatore automatico (ABI Prism 310 Genetic Analyzer). Risultati: Il rapporto MtDNA/nDNA nell’EBC dei pazienti IPF è risultato essere più alto rispetto al gruppo di controllo (16.59 ± 10.30 vs 7.94 ± 4.56; p < 0.005). I livelli di MtDNA/nDNA hanno mostrato una correlazione negativa con il FVC% (R = -0.4879, p 0.006) e con il FEV1% (R = -0.4364, p = 0.018). Inoltre, i livelli di Periostina misurati erano più alti nell'EBC dei pazienti IPF rispetto al gruppo di controllo (65,5 ± 23,5 pg/mL vs 33 ± 21,4 pg/mL, p <0.05), rispettivamente. Alterazioni dei microsatelliti sono state evidenziate nel 58,82% dei campioni di EBC analizzati e nel 12,50% dei corrispettivi campioni di sangue dei pazienti IPF (p <0,01). Nessuno dei soggetti controllo ha mostrato MAs nei marcatori studiati. Conclusioni: Un aumento del rapporto MtDNA/nDNA nei pazienti IPF suggerisce la presenza di una disfunzione mitocondriale a conferma del ruolo dello stress ossidativo in questa patologia. Inoltre, abbiamo dimostrato la possibilità di dosare la Periostina nelle vie aeree e i livelli di quest’ultima sono risultati essere più alti nei pazienti IPF. A differenza della Periostina sierica, la Periostina delle vie aeree potrebbe rappresentare un utile marker per meglio comprendere la patogenesi dell'IPF. Infine, abbiamo riportato che le alterazioni genetiche, rilevate nell’EBC, potrebbero avere un ruolo importante nelle complesse basi genetiche dell'IPF.Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology, which leads rapidly to death. As the diagnosis of IPF is complex, the search for non invasive biomarkers is of great relevance in consideration of the management of these patients. The aim of this study was to investigate in exhaled breath condensate (EBC) of IPF patients the mitochondrial DNA (MtDNA) alterations, as oxidative stress marker, and the potential role of Periostin and genetic microsatellite alterations (MAs) in IPF pathogenesis. Methods: 48 IPF patients were compared with 20 control subjects. Patients underwent EBC and blood collection. Content of mitochondrial DNA (MtDNA) and nuclear DNA (nDNA) was measured in EBC by Real Time PCR and the ratio between MtDNA/nDNA was calculated. Periostin was assessed by an enzyme-linked immunosorbent assay kit on EBC. Four microsatellite markers (THRA1, D17S579, D17S250 and D8S137) were used for the analysis of MAs. The EBC-DNA and WB-DNA were amplified by PCR; PCR products were analyzed using the ABI Prism 310 Genetic Analyzer. Results: Exhaled MtDNA/nDNA was higher in IPF patients compared to healthy controls (16.59 ± 10.30 vs 7.94 ± 4.56; p < 0.005). The level of MtDNA/nDNA was negatively correlated with FVC% (R = -0.4879, p = 0.006) and FEV1% (R = -0.4364, p = 0.018). Moreover, we were able to detect higher Periostin levels in the EBC of patients with IPF compared control subjects (65,5 ± 23,5 pg/mL vs 33 ± 21,4 pg/mL, p<0.05), respectively. MAs were found in 58.82 % of EBC-DNA and 12.50 % of WB-DNA in patients with IPF (p < 0.01). None of the healthy subjects exhibited MAs in the studied markers. Conclusions: There is an increase of MtDNA/nDNA ratio in IPF subjects that led us to suggest that there is a presence of mitochondrial dysfunction that confirms an important role of the oxidative stress in IPF. We also found that Periostin is measurable in the airways and increased in patients with IPF. Unlike serum Periostin, which may be derived from several sources outside the lung, airways Periostin could be a useful marker to better understanding the pathogenesis of IPF. Furthermore, we reported that the genetic alterations, studied in EBC, may play an important role in the complex genetic basis of IPF

Re-Evaluation of the Taxonomy of Talaromyces minioluteus

Talaromyces minioluteus belongs to the section Trachyspermi, has a worldwide distribution and has been found on various substrates, especially on various (stored) food commodities and indoor environments. This species is phenotypically and phylogenetically closely related to T. chongqingensis and T. minnesotensis. The phylogenetic and morphological analyses of 37 strains previously identified as T. chongqingensis, T. minnesotensis and T. minioluteus revealed that this clade incudes eight species: the accepted species T. chongqingensis, T. minnesotensis and T. minioluteus, the newly proposed species T. calidominioluteus, T. africanus and T. germanicus, and the new combinations T. gaditanus (basionym Penicillium gaditanum) and T. samsonii (basionym Penicillium samsonii). In this study, we give insight of the phylogenetic relationships and provide detailed descriptions of the species belonging to this clade. Macromorphological features, especially colony growth rates, texture and conidial colors on agar media, are important characters for phenotypic differentiation between species

Obstructive Sleep Apnea: A Look towards Micro-RNAs as Biomarkers of the Future

Sleep-disordered breathing (SDB) includes a broad spectrum of diseases, of which obstructive sleep apnea syndrome (OSA) is the most clinically significant manifestation. OSA is a respiratory disorder characterized by episodes of complete or partial obstruction of the upper airways that disturb ventilation and sleep architecture. In recent years, interest in the clinical implications of OSA seems to have increased, probably due to the numerous studies that have shown the existence of an important correlation between OSA and cardiovascular, dysmetabolic, and neoplastic changes. The guidelines currently available highlight the importance of diagnosis and effective treatment for OSA, underlining the need for new biomarkers that are useful in clinical practice, feasible, and reproducible to guide medical decision making. In this review, we intend to provide an overview of the potential role of microRNAs as new indicators for OSA management. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in RNA silencing and regulation of gene expression at the post-transcriptional level. These can bind specifically to their target genes by forming silencing complexes, thus inducing degradation or altered gene expression. A wide range of miRNAs have been extensively studied in a variety of diseases including cancer, and recently, miRNAs have been shown to have enormous potential to function as diagnostic and clinical biomarkers of disease. This review includes recent studies that establish the inevitable role of miRNAs in the pathogenesis of OSA

The Potential Role of Airways Periostin in the Clinical Practice of Patients Affected by Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic debilitating fibrotic lung disease leading to respiratory failure and ultimately to death. Noninvasive biomarkers, for the early diagnosis, differential diagnosis, prognosis, and prediction of therapeutic response, are needed. Previous studies support a role for periostin in lung fibrosis. The aim of our study was to analyze periostin levels in the airways of patients with IPF and to investigate its role as a useful predictive biomarker of the disease. We enrolled 30 IPF patients and 5 control subjects. All subjects underwent all standard radiological, functional, and biological examinations for IPF diagnosis and staging and exhaled breath condensate (EBC) collection. Periostin was assessed by an enzyme-linked immunosorbent assay kit on EBC. Periostin was dosable in the EBC of all subjects enrolled. We found higher exhaled periostin levels in IPF patients than healthy controls (65.5 +/- 23.5 pg/mL vs. 33 +/- 21.4 pg/mL, p < 0.05). Moreover, in receiver operating characteristic analysis, the clinical reference value of periostin was 37.88 pg/mL to discriminate patients with IPF from healthy subjects, with the area under the curve of 0.8815. There was no significant correlation between periostin levels and gender or pulmonary function tests. These preliminary results support our working hypothesis that periostin is dosable in the airways of patients with IPF. As the circulating periostin, also airways periostin may be a potential biomarker to support IPF diagnosis and to monitor disease progression during follow-up

Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach

Background: Extracellular vesicles (EVs) are secreted by cells from their membrane within circulation and body fluids. Knowledge of the involvement of EVs in pathogenesis of lung diseases is increasing. The present study aimed to evaluate the expression of exosomal surface epitopes in a cohort of idiopathic pulmonary fibrosis (IPF) patients followed in two Italian Referral Centres for Interstitial Lung Diseases, comparing them with a group of healthy volunteers. Materials and Methods: Ninety IPF patients (median age and interquartile range (IQR) 71 (66-75) years; 69 males) were selected retrospectively. Blood samples were obtained from patients before starting antifibrotic therapy. A MACSPlex Exosome Kit, human, (Miltenyi Biotec, Bergisch-Gladbach, Germany), to detect 37 exosomal surface epitopes, was used. Results: CD19, CD69, CD8, and CD86 were significantly higher in IPF patients than in controls (p = 0.0023, p = 0.0471, p = 0.0082, and p = 0.0143, respectively). CD42a was lower in IPF subjects than in controls (p = 0.0153), while CD209, Cd133/1, MCSP, and ROR1 were higher in IPF patients than in controls (p = 0.0007, p = 0.0050, p = 0.0139, and p = 0.0335, respectively). Kaplan-Meier survival analysis for IPF patients: for median values and a cut-off of 0.48 for CD25, the two subgroups showed a significant difference in survival rate (p = 0.0243, hazard ratio: 0.52 (95%CI 0.29-0.92); the same was true for CD8 (cut-off 1.53, p = 0.0309, hazard ratio: 1.39 (95%CI 0.75-2.53). Conclusion: Our multicenter study showed for the first time the expression of surface epitopes on EVs from IPF patients, providing interesting data on the communication signatures/exosomal profile in serum from IPF patients and new insights into the pathogenesis of the disease and a promising reliability in predicting mid-term survival of IPF patients

Controlling Nutritional Status Score as a Predictor for Chronic Obstructive Pulmonary Disease Exacerbation Risk in Elderly Patients

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to assess poor nutritional status as well as to predict clinical adverse outcomes in different clinical settings. No data are available in older patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the CONUT score as a predictor of frequent exacerbations. We retrospectively enrolled 222 patients aged 65 years or older, classified in two groups according to the number of exacerbations (or hospitalizations because AECOPD) during the previous year. The two groups were further divided according to low (p < 0.001) of the occurrence of ≥2 exacerbations (or 1 hospitalization) during the previous year. The CONUT score seemed to have a high prognostic value for frequent exacerbations for COPD in older patients. The predictive role of different CONUT score cut-off values needs to be validated in larger COPD populations in future multi-center, prospective clinical studies

EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell&ndash;cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers