Publications by authors named "Michelino Di Rosa"

80 Publications

Brain Expression Correlates with and in Healthy Subjects and AD Patients.

Cells 2021 Apr 13;10(4). Epub 2021 Apr 13.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95123 Catania, Italy.

Alzheimer's disease is a progressive, devastating, and irreversible brain disorder that, day by day, destroys memory skills and social behavior. Despite this, the number of known genes suitable for discriminating between AD patients is insufficient. Among the genes potentially involved in the development of AD, there are the chitinase-like proteins (CLPs) CHI3L1, CHI3L2, and CHID1. The genes of the first two have been extensively investigated while, on the contrary, little information is available on CHID1. In this manuscript, we conducted transcriptome meta-analysis on an extensive sample of brains of healthy control subjects (n = 1849) (NDHC) and brains of AD patients (n = 1170) in order to demonstrate CHID1 involvement. Our analysis revealed an inverse correlation between the brain expression levels and the age of NDHC subjects. Significant differences were highlighted comparing CHID1 expression of NDHC subjects and AD patients. Exclusive in AD patients, the expression levels were correlated positively to calcium-binding adapter molecule 1 () levels. Furthermore, both in NDHC and in AD patient's brains, the expression levels were directly correlated with calbindin 1 () and neurogranin (). According to brain regions, correlation differences were shown between the expression levels of in prefrontal, frontal, occipital, cerebellum, temporal, and limbic system. Sex-related differences were only highlighted in NDHC. CHID1 represents a new chitinase potentially involved in the principal processes underlying Alzheimer's disease.
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http://dx.doi.org/10.3390/cells10040882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069241PMC
April 2021

Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model.

Front Pharmacol 2021 30;12:652102. Epub 2021 Mar 30.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.652102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042260PMC
March 2021

The impact of physical exercise on hippocampus, in physiological condition and ageing-related decline: current evidence from animal and human studies.

Curr Pharm Biotechnol 2021 Apr 5. Epub 2021 Apr 5.

Department of Biomedical and Biotechnological Sciences, Human, Histology and Movement Science Section, University of Catania, Via S. Sofia n°87, Catania. Italy.

Physical exercise (PE), notoriously, promotes a state of general well-being, throughout the entire human lifespan. Moreover, maintaining an adequate and regular PE habit results to be a powerful preventive factor towards many diseases and may also help in managing existing pathological conditions. PE induces structural and functional changes in various districts of the body, determining biological and psychological benefits. Additionally, in elderly, PE might represent a remarkable tool reducing cognitive impairments related to the normal aging processes and it has also been found to have an impact in neurodegenerative diseases such as Alzheimer's disease. The present review aims to provide an overview about PE effects on hippocampus, since it is one of the brain regions most susceptible to aging and, therefore, involved in diseases characterized by cognitive impairment.
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http://dx.doi.org/10.2174/1389201022666210405142611DOI Listing
April 2021

Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature.

Int J Mol Sci 2021 Feb 28;22(5). Epub 2021 Feb 28.

Pediatric Pulmonology Unit, Department of Clinical and Experimental Medicine, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

In recent years, there has been a growth in scientific interest in nutraceuticals, which are those nutrients in foods that have beneficial effects on health. Nutraceuticals can be extracted, used for food supplements, or added to foods. There has long been interest in the antiviral properties of nutraceuticals, which are especially topical in the context of the ongoing COVID-19 pandemic. Therefore, the purpose of this review is to evaluate the main nutraceuticals to which antiviral roles have been attributed (either by direct action on viruses or by modulating the immune system), with a focus on the pediatric population. Furthermore, the possible applications of these substances against SARS-CoV-2 will be considered.
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http://dx.doi.org/10.3390/ijms22052465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957644PMC
February 2021

Hippocampal transcriptome deconvolution reveals differences in cell architecture of not demented elderly subjects underwent late-life physical activity.

J Chem Neuroanat 2021 Apr 11;113:101934. Epub 2021 Feb 11.

Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95125 Catania, Italy. Electronic address:

Recent findings demonstrated that physical exercise has a powerful role in improving cognitive function and delaying age-associated neurological decline. However, to date, there is a lack of information regarding the effect of physical activity (PA) on brain cells architecture. In this paper, we hypothesized that PA could play a role in the transcriptional changes of genes that enrich the main cells of central nervous system (CNS). From NCBI, we selected a microarray dataset composed of the human hippocampi (GSE110298) from 23 cognitively intact clinical cases (NDHSs) (aged 87.4 ± 6.3 years) selected to from the Rush Memory and Aging Project (MAP). The significantly expressed genes, obtained comparing hippocampi from subjects who underwent Low Physical Activity (LPA) vs those who performed High Physical Activity (HPA), were overlapped with the main genes enriching the CNS cells, obtained from the public human brain single-cell RNA-sequencing dataset (GSE67835), in order to determine the respective weighted percentages of significantly expression genes modulation (WPSEG). In NDHSs underwent HPA, the WPSEG was higher for Neurons, Dendritic Development, Synaptic transmission genes and Axon Development. In addition, in NDHSs underwent LPA we observed high expression of genes enriching Oligodendrocytes, Microglia, and Endothelial cells. Furthermore, neurogenesis and the decreasing of the T cell-mediated inflammatory process were the two main molecular mechanisms activated in the brains of NDHSs underwent HPA. From our results, it is possible to conclude that, in elderly subjects, the transcriptional profile of CNS cells changes as a function of the PA conducted during life. Performing PA periodically supports the maintenance of the physiological balance of neuronal cells and, consequently, improves the quality of life of the elderly.
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http://dx.doi.org/10.1016/j.jchemneu.2021.101934DOI Listing
April 2021

Focus on Osteosclerotic Progression in Primary Myelofibrosis.

Biomolecules 2021 01 19;11(1). Epub 2021 Jan 19.

Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hematopoietic stem-cell-derived clonal proliferation, leading to bone marrow (BM) fibrosis. Hematopoiesis alterations are closely associated with modifications of the BM microenvironment, characterized by defective interactions between vascular and endosteal niches. As such, neoangiogenesis, megakaryocytes hyperplasia and extensive bone marrow fibrosis, followed by osteosclerosis and bone damage, are the most relevant consequences of PMF. Moreover, bone tissue deposition, together with progressive fibrosis, represents crucial mechanisms of disabilities in patients. Although the underlying mechanisms of bone damage observed in PMF are still unclear, the involvement of cytokines, growth factors and bone marrow microenvironment resident cells have been linked to disease progression. Herein, we focused on the role of megakaryocytes and their alterations, associated with cytokines and chemokines release, in modulating functions of most of the bone marrow cell populations and in creating a complex network where impaired signaling strongly contributes to progression and disabilities.
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http://dx.doi.org/10.3390/biom11010122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832894PMC
January 2021

GNG13 Is a Potential Marker of the State of Health of Alzheimer's Disease Patients' Cerebellum.

J Mol Neurosci 2021 May 15;71(5):1046-1060. Epub 2020 Oct 15.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.

Brain regions such as the cerebellum (CB) have been neglected for a long time in the study of Alzheimer's disease (AD) pathogenesis. In reference to a new emerging hypothesis according to which there is an altered cerebellar synaptic processing in AD, we verified the possible role played by new biomarkers in the CB of AD patients compared with not-demented healthy control subjects (NDHS). Using a bioinformatics approach, we have collected several microarray datasets and obtained 626 cerebella sample biopsies belonging to subjects who did not die from causes related to neurological diseases and 199 cerebella belonging to AD. The analysis of logical relations between the transcriptome dataset highlighted guanine nucleotide-binding protein (G protein) gamma 13 (GNG13) as a potential new biomarker for Purkinje cells (PCs). We have correlated GNG13 expression levels with already widely existing bibliography of PC marker genes, such as Purkinje cell protein 2 (PCP2), Purkinje cell protein 4 (PCP4), and cerebellin 3 (CBLN3). We showed that expression levels of GNG13 and PCP2, PCP4, and CBLN3 were significantly correlated with each other in NDHS and in AD and significantly reduced in AD patients compared with NDHS subjects. In addition, we highlighted a negative correlation between the expression levels of PC biomarkers and age. From the outcome of our investigation, it is possible to conclude that the identification of GNG13 as a potentially biomarker in PCs represents also a state of health of CB, in association with the expression of PCP2, PCP4, and CBLN3.
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http://dx.doi.org/10.1007/s12031-020-01726-1DOI Listing
May 2021

Postsynaptic damage and microglial activation in AD patients could be linked CXCR4/CXCL12 expression levels.

Brain Res 2020 12 16;1749:147127. Epub 2020 Sep 16.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy. Electronic address:

Alzheimer's disease (AD) is one of the most common forms of dementia with still unknown pathogenesis. Several cytokines and chemokines are involved in the pathogenesis of AD. Among the chemokines, the CXCR4/CXCL12 complex has been shown to play an important role in the pathogenetic development of AD. We investigated the expression levels of CXCR4 / CXCL12 in fifteen brain regions of healthy non-demented subjects (NDHC) (2139 sample) and AD patients (1170 sample) stratified according to sex and age. Furthermore, we correlated their expressions with the Neurogranin (NRGN) and CHI3L1 levels, two inflamm-aging markers. We highlighted that CXCR4 gene expression levels were age-correlated in the brain of NDHC subjects and that AD nullified this correlation. A similar trend, but diametrically opposite was observed for CXCL12. Its expression was decreased during the aging in both sexes, and in the brains of AD patients, it underwent an inversion of the trend, only and exclusively in females. Brains of AD patients expressed high CXCR4 and CHI3L1, and low CXCL12 and Neurogranin levels compared to NDHC subjects. Both CXCR4 and CXCL12 correlated significantly with CHI3L1 and Neurogranin expression levels, regardless of disease. Furthermore, we showed a selective modulation of CXCL12 and CXCR4 only in specific brain regions. Taken together our results demonstrate that CXCL12 and CXCR4 are linked to Neurogranin and CHI3L1 expression levels and the relationship between postsynaptic damage and microglial activation in AD could be shown using all these genes. Further confirmations are needed to demonstrate the close link between these genes.
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http://dx.doi.org/10.1016/j.brainres.2020.147127DOI Listing
December 2020

Network perturbation analysis in human bronchial epithelial cells following SARS-CoV2 infection.

Exp Cell Res 2020 10 28;395(2):112204. Epub 2020 Jul 28.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy. Electronic address:

Background: SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach.

Methods: In the present investigation, we evaluated the effects of SARS-CoV on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV, SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses.

Results: The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor (CSF3) and dynein heavy chain 7, axonemal (DNAH7) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) that codifies for a surface protein is highly specific of SARS-CoV and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV infection.

Conclusions: Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.
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http://dx.doi.org/10.1016/j.yexcr.2020.112204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386311PMC
October 2020

The Role of Inflammation and Inflammasome in Myeloproliferative Disease.

J Clin Med 2020 Jul 22;9(8). Epub 2020 Jul 22.

Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are rare hematological conditions known as myeloproliferative neoplasms (MPNs). They are characterized for being negative malignancies and affected patients often present with symptoms which can significantly impact their quality of life. MPNs are characterized by a clonal proliferation of an abnormal hematopoietic stem/progenitor cell. In MPNs; cells of all myeloid lineages; including those involved in the immune and inflammatory response; may belong to the malignant clone thus leading to an altered immune response and an overexpression of cytokines and inflammatory receptors; further worsening chronic inflammation. Many of these cytokines; in particular, IL-1β and IL-18; are released in active form by activating the inflammasome complexes which in turn mediate the inflammatory process. Despite this; little is known about the functional effects of stem cell-driven inflammasome signaling in MPN pathogenesis. In this review we focused on the role of inflammatory pathway and inflammasome in MPN diseases. A better understanding of the inflammatory-state-driving MPNs and of the role of the inflammasome may provide new insights on possible therapeutic strategies.
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http://dx.doi.org/10.3390/jcm9082334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464195PMC
July 2020

CHI3L2 Expression Levels Are Correlated with AIF1, PECAM1, and CALB1 in the Brains of Alzheimer's Disease Patients.

J Mol Neurosci 2020 Oct 23;70(10):1598-1610. Epub 2020 Jul 23.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.

Alzheimer's disease (AD) represents one of the main forms of dementia that afflicts our society. The expression of several genes has been associated with disease development. Despite this, the number of genes known to be capable of discriminating between AD patients according to sex remains deficient. In our study, we performed a transcriptomes meta-analysis on a large court of brains of healthy control subjects (n = 2139) (NDHC) and brains of AD patients (n = 1170). Our aim was to verify the brain expression levels of CHI3L2 and its correlation with genes associated with microglia-mediated neuroinflammation (IBA1), alteration of the blood-brain barrier (PECAM1), and neuronal damage (CALB1). We showed that the CHI3L2, IBA1, PECAM1, and CALB1 expression levels were modulated in the brains of patients with AD compared to NDHC subjects. Furthermore, both in NDHC and in AD patient's brains, the CHI3L2 expression levels were directly correlated with IBA1 and PECAM1 and inversely with CALB1. Additionally, the expression levels of CHI3L2, PECAM1, and CALB1 but not of IBA1 were sex-depended. By stratifying the samples according to age and sex, correlation differences emerged between the expression levels of CHI3L2, IBA1, PECAM1, and CALB1 and the age of NDHC subjects and AD patients. CHI3L2 represents a promising gene potentially involved in the key processes underlying Alzheimer's disease. Its expression in the brains of sex-conditioned AD patients opens up new possible sex therapeutic strategies aimed at controlling imbalance in disease progression.
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http://dx.doi.org/10.1007/s12031-020-01667-9DOI Listing
October 2020

Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis.

Liver Int 2020 11 4;40(11):2820-2827. Epub 2020 Aug 4.

Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.

Background And Aims: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance.

Methods: We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F (F -isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression.

Results: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT ≥ 0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92 ± 0.20 vs 0.83 ± 0.21 mm, P < .001). HCV eradication markedly decreased serum levels of F -isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/mL, P < .0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/μl, P < .0001) and 8-hydroxy-2'-deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/mL, P < .0001), whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/mL, P = .001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF -isoprostanes (β: 1.746 [0.948; 2.543]; P < .0001) after adjustment for age, baseline F -isoprostanes and baseline IMT.

Conclusions: Besides association of lipid peroxidation with severity of liver disease, the reduction in F -isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication.
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http://dx.doi.org/10.1111/liv.14608DOI Listing
November 2020

The impact of physical activity on psychological health during Covid-19 pandemic in Italy.

Heliyon 2020 Jun 24;6(6):e04315. Epub 2020 Jun 24.

Department of Biomedical and Biotechnological Sciences, Human, Histology and Movement Science Section, University of Catania, Via S. Sofia n°87, 95123, Catania, Italy.

The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic. The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health. A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET-min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET-min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET-min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET-min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population. Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311901PMC
June 2020

Increased expression of connexin 43 in a mouse model of spinal motoneuronal loss.

Aging (Albany NY) 2020 06 24;12(13):12598-12608. Epub 2020 Jun 24.

Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy.

Amyotrophic lateral sclerosis (ALS) is one of the most common motoneuronal disease, characterized by motoneuronal loss and progressive paralysis. Despite research efforts, ALS remains a fatal disease, with a survival of 2-5 years after disease onset. Numerous gene mutations have been correlated with both sporadic (sALS) and familiar forms of the disease, but the pathophysiological mechanisms of ALS onset and progression are still largely uncertain. However, a common profile is emerging in ALS pathological features, including misfolded protein accumulation and a cross-talk between neuroinflammatory and degenerative processes. In particular, astrocytes and microglial cells have been proposed as detrimental influencers of perineuronal microenvironment, and this role may be exerted via gap junctions (GJs)- and hemichannels (HCs)-mediated communications. Herein we investigated the role of the main astroglial GJs-forming connexin, Cx43, in human ALS and the effects of focal spinal cord motoneuronal depletion onto the resident glial cells and Cx43 levels. Our data support the hypothesis that motoneuronal depletion may affect glial activity, which in turn results in reactive Cx43 expression, further promoting neuronal suffering and degeneration.
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http://dx.doi.org/10.18632/aging.103561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377853PMC
June 2020

The expression levels of CHI3L1 and IL15Rα correlate with TGM2 in duodenum biopsies of patients with celiac disease.

Inflamm Res 2020 Sep 4;69(9):925-935. Epub 2020 Jun 4.

Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.

Objective And Design: Celiac disease (CD) is an intestinal inflammatory disorder of the small intestine. Gliadins are a component of gluten and there are three main types (α, γ, and ω). Recent studies indicate that gliadin peptides are able to activate an innate immune response. IL15 is a major mediator of the innate immune response and is involved in the early alteration of CD mucosa. The chitinase molecules are highly expressed by the innate immune cells during the inflammatory processes.

Material Or Subjects: We analyzed several microarray datasets of PBMCs and duodenum biopsies of CD patients and healthy control subjects (HCs). We verified the modulation CHI3L1 in CD patients and correlated the expression levels to the IL15, IL15Rα, TGM2, IFNγ, and IFNGR1/2. Duodenal biopsy samples belonged to nine active and nine treated children patients (long-term effects of gliadin), and 17 adult CD patients and 10 adults HCs. We also selected 169 samples of PBMCs from 127 CD patients on adherence to a gluten-free diet (GFD) for at least 2 years and 44 HCs.

Results: Our analysis showed that CHI3L1 and IL15Rα were significantly upregulated in adult and children's celiac duodenum biopsies. In addition, the two genes were correlated significantly both in children than in adults CD duodenum biopsies. No significant modulation was observed in PBMCs of adult CD patients compared to the HCs. The correlation analysis of the expression levels of CHI3L1 and IL15Rα compared to TGM showed significant values both in adults and in children duodenal biopsies. Furthermore, the IFNγ expression levels were positively correlated with CHI3L1 and IL15Rα. Receiver operating characteristic (ROC) analysis confirmed the diagnostic ability of CHI3L1 and IL15Rα to discriminate CD from HCs.

Conclusion: Our data suggest a role for CHI3L1 underlying the pathophysiology of CD and represent a starting point aiming to inspire new investigation that proves the possible use of CHI3L1 as a diagnostic factor and therapeutic target.
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http://dx.doi.org/10.1007/s00011-020-01371-9DOI Listing
September 2020

Long-Term Results of the Mediterranean Diet After Sleeve Gastrectomy.

Obes Surg 2020 Oct;30(10):3792-3802

Department of Medicine, Surgery, and Dentistry, "Scuola Medica Salernitana", University of Salerno, Fisciano, Italy.

Background: To assess dietary habits in a cohort of patients at minimum follow-up of 4 years after sleeve gastrectomy (SG) by comparing their dietary records to the Italian Mediterranean diet (IMD) recommendations.

Methods: We prospectively evaluated in 74 patients who had the SG in 2014 dietary habits by a 7-day food dietary records, weight and micronutrient status, evolution of comorbidities, use of micronutrient supplements, and frequency of physical activity.

Results: The IMD recommendations in terms of daily/weekly portions of fruits, vegetables, and complex carbohydrates were followed by 40.5%, 35.1%, and 40.5% of the participants, respectively. Concerning milk/dairy, olive oil, poultry, fish/shellfish, eggs, legumes, processed/red meat, and cold cuts, 54.1%, 85.1%, 44.5%, 75.7%, 67.6%, 35.1%, 87.8%, and 55.4% of the participants, respectively, followed the IMD recommendations. Weight regain appeared in 37.8% of participants, while physical activity was reported by the 54.0% of them. Deficiencies of vitamin B12, vitamin D, folate, iron, and anemia were found present in 6.8%, 8.1%, 24.3%, 33.8%, and 59.5% of the participants, respectively, and 18.9% of them were found to take micronutrient supplements. Improvement/remission of type 2 diabetes, hypertension, or obstructive sleep apnea was 73.3%, 64.7%, and 100% respectively.

Conclusions: In this prospective cohort with a minimum follow-up of 4 years after SG, we found an inadequate intake of fruit, vegetables, poultry, and complex carbohydrates according to the IMD recommendations; the frequency of physical activity and the use of micronutrients supplements were also inadequate. This may contribute to weight regain and micronutrient deficiencies in the long term.
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http://dx.doi.org/10.1007/s11695-020-04695-xDOI Listing
October 2020

Heme Oxygenase-1 in Central Nervous System Malignancies.

J Clin Med 2020 May 21;9(5). Epub 2020 May 21.

Department of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

Central nervous system tumors are the most common pediatric solid tumors and account for 20%-25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas.
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http://dx.doi.org/10.3390/jcm9051562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290325PMC
May 2020

Evaluation of a Cell-Free Collagen Type I-Based Scaffold for Articular Cartilage Regeneration in an Orthotopic Rat Model.

Materials (Basel) 2020 May 21;13(10). Epub 2020 May 21.

Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy.

The management of chondral defects represents a big challenge because of the limited self-healing capacity of cartilage. Many approaches in this field obtained partial satisfactory results. Cartilage tissue engineering, combining innovative scaffolds and stem cells from different sources, emerges as a promising strategy for cartilage regeneration. The aim of this study was to evaluate the capability of a cell-free collagen I-based scaffold to promote cartilaginous repair after orthotopic implantation in vivo. Articular cartilage lesions (ACL) were created at the femoropatellar groove in rat knees and cell free collagen I-based scaffolds (S) were then implanted into right knee defect for the ACL-S group. No scaffold was implanted for the ACL group. At 4-, 8- and 16-weeks post-transplantation, degrees of cartilage repair were evaluated by morphological, histochemical and gene expression analyses. Histological analysis shows the formation of fibrous tissue, at 4-weeks replaced by a tissue resembling the calcified one at 16-weeks in the ACL group. In the ACL-S group, progressive replacement of the scaffold with the newly formed cartilage-like tissue is shown, as confirmed by Alcian Blue staining. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses display the expression of typical cartilage markers, such as collagen type I and II ( and ), and . The results of this study display that the collagen I-based scaffold is highly biocompatible and able to recruit host cells from the surrounding joint tissues to promote cartilaginous repair of articular defects, suggesting its use as a potential approach for cartilage tissue regeneration.
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http://dx.doi.org/10.3390/ma13102369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287598PMC
May 2020

Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells.

Aging (Albany NY) 2020 05 12;12(10):9745-9760. Epub 2020 May 12.

Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic.

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.
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http://dx.doi.org/10.18632/aging.103241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288915PMC
May 2020

Immunoproteasome Genes Are Modulated in CD34 JAK2 Mutated Cells from Primary Myelofibrosis Patients.

Int J Mol Sci 2020 Apr 22;21(8). Epub 2020 Apr 22.

Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95125 Catania, Italy.

Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by stem-cell-derived clonal over-proliferation of mature myeloid lineages, bone marrow fibrosis, osteosclerosis, defective erythropoiesis, and pro-inflammatory cytokine over-expression. The aim of the present study was to highlight possible differences in the transcriptome among CD34 cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2 MUTATED and 28 JAK2 wild-type). The GO analysis of upregulated genes revealed enrichment for JAK2/STAT1 pathway gene set in PB CD34 cells of PMF patients with and without the comparing to the healthy control subjects, and in particular a significant upregulation of immunoproteasome (IP)-belonging genes as , and A more detailed investigation of the IFN-gamma (IFNG) pathway also revealed that and were significantly upregulated in PB CD34 cells of PMF patients carrying the mutation for JAK2 compared to JAK2 wild-type PMF patients. Finally, we showed an upregulation of HLA-class I genes in PB CD34 cells from PMF JAK2 mutated patients compared to JAK2 wild-type and healthy controls. In conclusion, our results demonstrate that IPs and IFNG pathways could be involved in PMF disease and in particular in patients carrying the .
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http://dx.doi.org/10.3390/ijms21082926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216198PMC
April 2020

Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells.

Mol Neurobiol 2020 May 27;57(5):2436-2446. Epub 2020 Feb 27.

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125, Catania, Italy.

In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its selective enzymatic inhibition in two different cell lines (i.e. A172 and U87-MG). HO-1 was induced by hemin treatment (10 μM), and VP13/47 (100 μM) was used as a specific non-competitive inhibitor of HO-1 activity. Cell proliferation was measured by cell index measurement (xCelligence technology) and clonogenic assay, whereas cell migration was assessed by wound healing assay. Carbon monoxide-releasing molecules (CORMs) (i.e. CORM-3 and CORM-A1) were also used in a separate set of experiments to confirm the effect of HO-1 by-product in glioblastoma progression further. Our results were further validated using GSE4412 microarray dataset analysis and comparing biopsies overexpressing HO-1 with the rest of the cases. Our results showed that hemin was able to induce both HO-1 gene and protein expression in a cell-dependent manner being A172 more responsive to pharmacological upregulation of HO-1. Hemin, but not CORMs treatment, resulted in a significant increase of cell proliferation following 24 h of treatment as measured by increased cell index and colony formation capacity and such effect was abolished by VP13/47. Interestingly, both hemin and CORMs showed a significant effect on the wound healing assay also exhibiting cell specificity. Finally, our dataset analysis showed a positive correlation of HO-1 gene expression with ITGBI and ITGBII which are membrane receptors involved in cell adhesion, embryogenesis, tissue repair, immune response and metastatic diffusion of tumour cells. In conclusion, our data suggest that HO-1 and its by-product CO exhibit a cell-specific effect on various aspects of disease progression and are associated with a complex series of molecular mechanisms driving cell proliferation, survival and metastasis.
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http://dx.doi.org/10.1007/s12035-020-01869-7DOI Listing
May 2020

Investigating lubricin and known cartilage-based biomarkers of osteoarthritis.

Expert Rev Mol Diagn 2020 04 24;20(4):443-452. Epub 2020 Feb 24.

Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, Catania, Via Santa Sofia, Italy.

: Osteoarthritis (OA) is a degenerative disease which primarily affects hyaline cartilage, leading to pain, stiffness and loss of mobility of the entire articulation. Diagnosis is commonly based on symptoms and radiographs, but there is a growing interest in detecting novel biomarkers, in serum, urine and synovial fluid, which can be predictors of disease onset and progression.: This review provides an overview of the main biomarkers currently used in OA clinical practice, with a focus on lubricin, a surface glycoprotein secreted in the synovial fluid that lubricates the cartilage and reduces the coefficient of friction within the joint. Key findings of the last years are presented throughout the article.: Analysis of biomarkers might suggest personalized protocols of treatment, guide the classification of OA phenotypes, contribute to precision medicine, avoid further unnecessary exams, facilitate drug discovery or refine treatment guidelines. For all these reasons, the investigation of novel cartilage-based biomarker of osteoarthritis needs to be promoted and improved.
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http://dx.doi.org/10.1080/14737159.2020.1733978DOI Listing
April 2020

Non-competitive heme oxygenase-1 activity inhibitor reduces non-small cell lung cancer glutathione content and regulates cell proliferation.

Mol Biol Rep 2020 Mar 13;47(3):1949-1964. Epub 2020 Feb 13.

Department of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death mainly due to its high metastatic rate. Impairment of redox homeostasis mechanisms has been previously described in NSCLC and is associated with the disease itself as well as with comorbidities such as smoking. The aim of the present in vitro study was to evaluate the effect of selective and non-competitive inhibition of heme oxygenase-1 (HO-1) on cancer redox homeostasis with particular regards to glutathione (GSH) metabolism related enzymes. NSCLC cell line (A549) was treated with the HO-1 activity inhibitor VP13/47 (10 µM) and we further evaluated cell viability, apoptosis, mitochondrial dysfunction and oxidative stress. Our results showed that VP13/47 significantly reduced HO-1 expression and total HO activity thus, resulting in a significant reduction of cell viability, proliferation and increased apoptosis, mitochondrial dysfunction and oxidative stress. Consistently with increased oxidative stress, we also showed that reduced GSH was significantly decreased and such effect was also accompanied by a significant downregulation of the enzymes involved in its biosynthesis. Taken all together our results show that selective HO-1 inhibition significantly impairs NSCLC progression and may represent a possible pharmacological strategy for new chemotherapy agents.
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http://dx.doi.org/10.1007/s11033-020-05292-yDOI Listing
March 2020

Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study.

Cells 2020 02 3;9(2). Epub 2020 Feb 3.

Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy.

Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG's ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG-CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG's cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG-CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.
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http://dx.doi.org/10.3390/cells9020347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072395PMC
February 2020

Ixazomib Improves Bone Remodeling and Counteracts sonic Hedgehog signaling Inhibition Mediated by Myeloma Cells.

Cancers (Basel) 2020 Jan 30;12(2). Epub 2020 Jan 30.

Division of Hematology, Department of General Surgery and Medical-Surgical Specialties, A.O.U. "Policlinico-Vittorio Emanuele", University of Catania, 95123 Catania, Italy.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of plasma cells (PC) in the bone marrow (BM), leading to bone loss and BM failure. Osteolytic bone disease is a common manifestation observed in MM patients and represents the most severe cause of morbidity, leading to progressive skeletal damage and disabilities. Pathogenetic mechanisms of MM bone disease are closely linked to PCs and osteoclast (OCs) hyperactivity, coupled with defective osteoblasts (OBs) function that is unable to counteract bone resorption. The aim of the present study was to investigate the effects of Ixazomib, a third-generation proteasome inhibitor, on osteoclastogenesis and osteogenic differentiation. We found that Ixazomib was able to reduce differentiation of human monocytes into OCs and to inhibit the expression of OC markers when added to the OC medium. Concurrently, Ixazomib was able to stimulate osteogenic differentiation of human mesenchymal stromal cells (MSCs), increasing osteogenic markers, either alone or in combination with the osteogenic medium. Given the key role of Sonic Hedgehog (SHH) signaling in bone homeostasis, we further investigated Ixazomib-induced SHH pathway activation. This set of experiments showed that Ixazomib, but not Bortezomib, was able to bind the Smoothened (SMO) receptor leading to nuclear translocation of GLI1 in human MSCs. Moreover, we demonstrated that PCs act as GLI1 suppressors on MSCs, thus reducing the potential of MSCs to differentiate in OBs. In conclusion, our data demonstrated that Ixazomib regulates bone remodeling by decreasing osteoclastogenesis and prompting osteoblast differentiation via the canonical SHH signaling pathway activation, thus, representing a promising therapeutic option to improve the complex pathological condition of MM patients.
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http://dx.doi.org/10.3390/cancers12020323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073172PMC
January 2020

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

Dermatol Ther 2020 01 9;33(1):e13180. Epub 2019 Dec 9.

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4 count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.
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http://dx.doi.org/10.1111/dth.13180DOI Listing
January 2020

Focal Neuropathy Mimicking Focal Dystonia in a Child: Diagnostic and Rehabilitative Tools.

J Funct Morphol Kinesiol 2019 Aug 5;4(3). Epub 2019 Aug 5.

Department of Biomedical and Biotechnological Sciences, University of Catania-U.O. Rehabilitation A.O.U. "Policlinico-Vittorio Emanuele", 95123 Catania, Italy.

Object: Focal neuropathy results from an injury of any etiology that occurs in a peripheral nerve. The lesion may be followed by alteration of the sensory sphere (either dysesthesia or paresthesia with or without neuropathic pain), or by compensatory attitudes that are attributable to the altered contraction in muscles that are innervated by the injured nerve.

Methods: We describe the case of a 13-year-old boy who attended our hospital for a focal neuropathy of the radial nerve.

Conclusion: This neuropathy was revealed after the removal of a plaster Zimmer splint that was applied following a post-traumatic subluxation of the metacarpal-trapezoid joint.
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http://dx.doi.org/10.3390/jfmk4030054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739221PMC
August 2019

Sex difference in CHI3L1 expression levels in human brain aging and in Alzheimer's disease.

Brain Res 2019 10 24;1720:146305. Epub 2019 Jun 24.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Italy. Electronic address:

Several genetic sexual dimorphisms have been identified in animal and human brains, which may form a neural basis for sex-specific predisposition to neurological diseases. In the last years, clinical studies have observed that Alzheimer's disease (AD) disproportionately affects women compared with men. Chitinase-3-Like 1 protein (CHI3L1) has been frequently investigated in body fluids as a surrogate marker of neuroinflammation in AD and other neurological disorders. Nevertheless, the sex-related differences in CHI3L1 expression in the human brain has not yet been investigated. Here we aimed to evaluate the specificity of increase of CHI3L1 in five brain regions (cerebellum, dorsolateral prefrontal cortex, prefrontal cortex, hippocampus, and visual cortex) of male and female controls during normal aging, as well as in AD patients. We selected ten microarray datasets from NCBI, representing normal aging (n = 1290) and AD (n = 992), and stratified the brain specimens according to age, gender and brain region. The expression levels of CHI3L1 were correlated with age and gender. Female control brain specimens showed higher CHI3L1 expression than male brains. The expression differences between men and women were most obvious in older subjects. The expression analysis of CHI3L1 in the different brain regions of AD subjects also showed sex differences; females with AD had greater expression in the cerebellum than males. Notably, sex-associated CHI3L1 expression differences in hippocampus disappeared in AD. These findings demonstrate that the expression of CHI3L1 in the brains of cognitively unimpaired subjects and AD patients is closely linked to age and sex, which was most obvious in the cerebellum. Further studies are needed to confirm our results.
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http://dx.doi.org/10.1016/j.brainres.2019.146305DOI Listing
October 2019

Assessment of Vitamin D Supplementation on Articular Cartilage Morphology in a Young Healthy Sedentary Rat Model.

Nutrients 2019 Jun 3;11(6). Epub 2019 Jun 3.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95123 Catania, Italy.

Deficiency in vitamin D (Vit D) has been widely associated with several musculoskeletal diseases. However, the effects of the exogenous Vit D supplementation are still unclear in the prevention of the latter, especially in the cartilage developmental period. The aim of this study was to compare the effects of Vit D supplementation and restriction on the articular cartilage development in healthy young sedentary rats. To this aim, twelve nine-week-old healthy Sprague-Dawley male rats were subjected to Vit D-based experimental diets: R, with a content in Vit D of 1400 IU/kg; R-DS, with a Vit D supplementation (4000 IU/kg); R-DR, with a Vit D restriction (0 IU/kg) for 10 weeks. The morphology, thickness and expression of cartilage-associated molecules such as collagen type II/X, lubricin and Vit D receptor (VDR), were assessed. Histological, histomorphometric and immunohistochemical evaluations were made on rat tibial cartilage samples. In the present experimental model, restriction of Vit D intake induced: The lower thickness of cartilage compared both to R ( = < 0.0001) and R-DS ( = < 0.0001); reduction of proteoglycans in the extracellular matrix (ECM) compared both to R ( = 0.0359) and R-DS ( = < 0.0001); decreased collagen II (Col II) with respect both to R ( = 0.0076) and R-DS ( = 0.0016); increased collagen X (Col X) immunoexpression when compared both to R ( = < 0.0001) and R-DS ( = < 0.0001), confirming data from the literature. Instead, supplementation of Vit D intake induced: Higher cartilage thickness with respect both to R ( = 0.0071) and R-DR ( = < 0.0001); increase of ECM proteoglycan deposition compared both to R ( = 0.0175) and R-DR ( = < 0.0001); higher immunoexpression of lubricin with respect both to R ( = 0.001) and R-DR ( = 0.0008). These results suggest that Vit D supplementation with diet, already after 10 weeks, has a favorable impact on the articular cartilage thickness development, joint lubrication and ECM fibers deposition in a young healthy rat model.
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http://dx.doi.org/10.3390/nu11061260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628271PMC
June 2019

Middle-aged healthy women and Alzheimer's disease patients present an overlapping of brain cell transcriptional profile.

Neuroscience 2019 May 12;406:333-344. Epub 2019 Mar 12.

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy. Electronic address:

Exploring sexual dimorphisms in the brain morphology is important for their impact and therapeutic implications for several neurological diseases. The hypothesis that sex could influence the transcriptome of brain cells could be the basis regarding the different response to cognitive decline identified in men and women. In this paper, we analyzed several prefrontal cortices (PFC) microarrays datasets of young/middle-aged healthy subjects and then Alzheimer's disease (AD) patients, according to the sex. The significant transcriptomes were overlapped with the main genes characterizing cells of the central nervous system (CNS) in order to determine the respective weighted percentages of significantly expression gene modulation (WPSEG). We identified differences in brain transcriptional activity between young and middle-aged. In middle-aged women, the WPSEG were higher for the Astrocytes, the Endotheliocytes, and the Microglia. In addition, the sex-matched analysis of transcriptome identified a convergent molecular signature in men and women AD patients. Furthermore, the WPSEG belonging to CNS cells in PFC of healthy middle-aged subjects was correlated to AD profiles according to the sex. Since our results, it is possible to conclude that during the aging the PFC' cells adopt transcriptional strategies sex-dependent that could potentially control the development of neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.neuroscience.2019.03.008DOI Listing
May 2019