Publications by authors named "Ersilia Nigro"

73 Publications

A novel smaller β-defensin-derived peptide is active against multidrug-resistant bacterial strains.

FASEB J 2021 12;35(12):e22026

Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.

Antibiotic resistance is becoming a severe obstacle in the fight against acute and chronic infectious diseases that accompany most degenerative illnesses from neoplasia to osteo-arthritis and obesity. Currently, the race is on to identify pharmaceutical molecules or combinations of molecules able to prevent or reduce the insurgence and/or progression of infectivity. Attempts to substitute antibiotics with antimicrobial peptides have, thus far, met with little success against multidrug-resistant (MDR) bacterial strains. During the last decade, we designed and studied the activity and features of human β-defensin analogs, which are salt-resistant, and hence active also under high salt concentrations as, for instance, in cystic fibrosis. Herein, we describe the design, synthesis, and major features of a new 21 aa long molecule, peptide γ2. The latter derives from the γ-core of the β-defensin natural molecules, a small fragment of these molecules still bearing high antibacterial activity. We found that peptide γ2, which contains only one disulphide bond, recapitulates most of the biological properties of natural human β-defensins and can also counteract both Gram-positive and Gram-negative MDR bacterial strains and biofilm formation. Moreover, it has great stability in human serum thereby enhancing its antibacterial presence and activity without cytotoxicity in human cells. In conclusion, peptide γ2 is a promising new weapon also in the battle against intractable infectious diseases.
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http://dx.doi.org/10.1096/fj.202002330RRDOI Listing
December 2021

AdipoRon negatively regulates proliferation and migration of ARPE-19 human retinal pigment epithelial cells.

Peptides 2021 Dec 22;146:170676. Epub 2021 Oct 22.

CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, "Federico II" Università degli Studi di Napoli, Napoli, 80131, Italy.

Adiponectin is an adipokine playing important roles in metabolic, inflammatory and proliferative processes. At the time of surgery for rhegmatogenous retinal detachment, an altered expression of adipokines has been associated with the development of future proliferative vitreoretinopathy (PVR); this evidence as well as the presence of adiponectin receptors in ocular tissues and cell lines suggests a role of adiponectin in the physio-pathology of ocular conditions. Here, we investigated the effects of AdipoRon, an adiponectin agonist, on ARPE-19, a human retinal pigment epithelial cell line after confirming the expression of AdipoR1, AdipoR2, T-cadherin receptors. We evaluated the effects of AdipoRon in terms of vitality, survival, and migration; furthermore, we investigated the potential effects of AdipoRon on the inflammatory state of ARPE-19 cells analysing the levels of IL-10, VEGF, MCP-1 and IL-6 cytokines. Our findings indicated that AdipoRon, in a time and dose-dependent manner, reduces cell proliferation, migration, and colony formation of ARPE-19 cells. On the contrary, AdipoRon administration does not affect the expression of the tested cytokines. In conclusion, our results indicated that AdipoRon, may constitute an endogenous inhibitor of retinal pigment epithelial cell proliferation and migration, both processes deeply involved in development of PVR. Since PVR are characterized by an aberrant growth, migration and dedifferentiation of retinal pigment epithelial cells, our data contribute to open new fields of research to develop innovative therapeutic targets. Further studies are needed to clarify the effects of AdipoRon and of other small-molecule adiponectin analogs on retinal epithelium to clarify the functional role of adiponectin.
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http://dx.doi.org/10.1016/j.peptides.2021.170676DOI Listing
December 2021

GDM-complicated pregnancies: focus on adipokines.

Mol Biol Rep 2021 Dec 15;48(12):8171-8180. Epub 2021 Oct 15.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100, Caserta, Italy.

Gestational diabetes mellitus (GDM) is a serious complication of pregnancy and is defined as a state of glucose intolerance that is first diagnosed and arises during gestation. Although the pathophysiology of GDM has not yet been thoroughly clarified, insulin resistance and pancreatic β-cell dysfunction are considered critical components of its etiopathogenesis. To sustain fetus growth and guarantee mother health, many significant changes in maternal metabolism are required in normal and high-risk pregnancy accompanied by potential complications. Adipokines, adipose tissue-derived hormones, are proteins with pleiotropic functions including a strong metabolic influence in physiological conditions and during pregnancy too. A growing number of studies suggest that various adipokines including adiponectin, leptin, visfatin, resistin and tumor necrosis factor α (TNF-α) are dysregulated in GDM and might have pathological significance and a prognostic value in this pregnancy disorder. In this review, we will focus on the current knowledge on the role that the aforementioned adipokines play in the development and progression of GDM.
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http://dx.doi.org/10.1007/s11033-021-06785-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604848PMC
December 2021

BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma.

J Biol Chem 2021 Nov 29;297(5):101223. Epub 2021 Sep 29.

Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom. Electronic address:

Malignant pleural mesothelioma (MPM) is a rare, aggressive, and incurable cancer arising from the mesothelial lining of the pleura, with few available treatment options. We recently reported that loss of function of the nuclear deubiquitinase BRCA1-associated protein 1 (BAP1), a frequent event in MPM, is associated with sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. As a potential underlying mechanism, here we report that BAP1 negatively regulates the expression of TRAIL receptors: death receptor 4 (DR4) and death receptor 5 (DR5). Using tissue microarrays of tumor samples from MPM patients, we found a strong inverse correlation between BAP1 and TRAIL receptor expression. BAP1 knockdown increased DR4 and DR5 expression, whereas overexpression of BAP1 had the opposite effect. Reporter assays confirmed wt-BAP1, but not catalytically inactive BAP1 mutant, reduced promoter activities of DR4 and DR5, suggesting deubiquitinase activity is required for the regulation of gene expression. Co-immunoprecipitation studies demonstrated direct binding of BAP1 to the transcription factor Ying Yang 1 (YY1), and chromatin immunoprecipitation assays revealed BAP1 and YY1 to be enriched in the promoter regions of DR4 and DR5. Knockdown of YY1 also increased DR4 and DR5 expression and sensitivity to TRAIL. These results suggest that BAP1 and YY1 cooperatively repress transcription of TRAIL receptors. Our finding that BAP1 directly regulates the extrinsic apoptotic pathway will provide new insights into the role of BAP1 in the development of MPM and other cancers with frequent BAP1 mutations.
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http://dx.doi.org/10.1016/j.jbc.2021.101223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545693PMC
November 2021

Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9.

Int J Mol Sci 2021 Jul 13;22(14). Epub 2021 Jul 13.

CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy.

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel's formation, to candidate them as therapeutic targets.
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http://dx.doi.org/10.3390/ijms22147516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307755PMC
July 2021

SARS-CoV-2: One Year in the Pandemic. What Have We Learned, the New Vaccine Era and the Threat of SARS-CoV-2 Variants.

Biomedicines 2021 May 27;9(6). Epub 2021 May 27.

Dipartimento di Scienze Mediche Traslazionali, University of Campania "L. Vanvitelli", 80131 Naples, Italy.

Since the beginning of 2020, the new pandemic caused by SARS-CoV-2 and named coronavirus disease 19 (COVID 19) has changed our socio-economic life. In just a few months, SARS-CoV-2 was able to spread worldwide at an unprecedented speed, causing hundreds of thousands of deaths, especially among the weakest part of the population. Indeed, especially at the beginning of this pandemic, many reports highlighted how people, suffering from other pathologies, such as hypertension, cardiovascular diseases, and diabetes, are more at risk of severe outcomes if infected. Although this pandemic has put the entire academic world to the test, it has also been a year of intense research and many important contributions have advanced our understanding of SARS-CoV-2 origin, its molecular structure and its mechanism of infection. Unfortunately, despite this great effort, we are still a long way from fully understanding how SARS-CoV-2 dysregulates organismal physiology and whether the current vaccines will be able to protect us from possible future pandemics. Here, we discuss the knowledge we have gained during this year and which questions future research should address.
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http://dx.doi.org/10.3390/biomedicines9060611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226851PMC
May 2021

AdipoRon and Other Adiponectin Receptor Agonists as Potential Candidates in Cancer Treatments.

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Dipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Napoli, Italy.

The high mortality rate together with an ever-growing number of annual cases have defined neoplastic disorders as "the real 21st-century disease". Its dubious distinction also results from conventional therapy failure, which has made cancer an orphan disease. Therefore, innovative and alternative therapeutic strategies are mandatory. The ability to leverage human naturally occurring anti-tumor defenses has always represented a fascinating perspective, and the immuno blockage approval in cancer treatment represents in timeline the latest success. As a multifunctional organ, adipose tissue releases a large amount of adipokines having both carcinogenic and antitumor properties. The negative correlation between serum levels and risk for developing malignancies, as well as the huge number of existing preclinical studies, have identified adiponectin as a potential anticancer adipokine. Nevertheless, its usage in clinical has constantly clashed with the inability to reproduce a mimic synthetic compound. Between 2011 and 2013, two distinct adiponectin receptor agonists were recognized, opening new scenarios even in cancer. Here, we review the first orally active adiponectin receptor agonists AdipoRon, from the discovery to the anticancer evidence. Including our latest findings in osteosarcoma models, we summarize AdipoRon and other existing agonists state-of-art, questioning about the feasibility assessment of this strategy in cancer treatment.
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http://dx.doi.org/10.3390/ijms22115569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197554PMC
May 2021

Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from L. Promising Compounds?

Molecules 2021 May 2;26(9). Epub 2021 May 2.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy.

L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for L. and the ongoing clinical trials.
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http://dx.doi.org/10.3390/molecules26092668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124362PMC
May 2021

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution.

Cancer Discov 2021 Oct 4;11(10):2456-2473. Epub 2021 May 4.

DSB Repair Metabolism Laboratory, The Francis Crick Institute, London, United Kingdom.

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when expression is induced during cancer development remains to be defined. Here we show that specific genes are upregulated in breast ductal carcinoma , and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE: This study reveals the dynamics and drivers of gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution..
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http://dx.doi.org/10.1158/2159-8290.CD-20-0725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487921PMC
October 2021

Physical Activity Regulates TNFα and IL-6 Expression to Counteract Inflammation in Cystic Fibrosis Patients.

Int J Environ Res Public Health 2021 04 28;18(9). Epub 2021 Apr 28.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche, Farmaceutiche, Università della Campania "Luigi Vanvitelli", 81100 Caserta, Italy.

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA.

Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays.

Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease ( = 0.023 and = 0.02, respectively), and positively correlated with serum fasting glucose ( = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 ( = 0.001) and negatively correlated with adiponectin ( = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state.

Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA.
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http://dx.doi.org/10.3390/ijerph18094691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125516PMC
April 2021

microRNA-377-3p downregulates the oncosuppressor T-cadherin in colorectal adenocarcinoma cells.

Cell Biol Int 2021 Aug 5;45(8):1797-1803. Epub 2021 May 5.

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli", Caserta, Italy.

Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for the adiponectin-receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of the T-cadherin receptor. In addition, the loss of T-cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this study explores their possible contribution to the downregulation of T-cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target miRNA sites within the 3' UTR of T-cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the T-cadherin sequence, and thus downregulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of T-cadherin in CRC, the regulatory circuit highlighted in this study may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets.
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http://dx.doi.org/10.1002/cbin.11605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360034PMC
August 2021

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Int J Environ Res Public Health 2021 03 1;18(5). Epub 2021 Mar 1.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy.

Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity. Therefore, the adhesion to an appropriate health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer, and improve the response to therapies. We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut-lung axis), are strictly related to dietary patterns and regular physical activity playing a key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.
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http://dx.doi.org/10.3390/ijerph18052399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967729PMC
March 2021

Dietary influence on adiponectin in patients with type 2 diabetes.

Eur J Clin Invest 2021 Aug 2;51(8):e13548. Epub 2021 Apr 2.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Background: Here, we evaluate the effects of a diet rich in low-glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D).

Methods: Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35-70 years, followed a CHO/Fibre diet or a MUFA diet for an 8-week period. Hepatic fat content by H NMR and fasting and postprandial plasma glucose and insulin measurements were also available.

Results: Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 ± 1.6 μg/mL vs. 10.8 ± 2.3 μg/mL; P = .033) but not after the MUFA diet (10.6 ± 1.8 μg/mL vs. 10.6 ± 1.6 μg/mL; P = .935) with a significant difference between changes (P = .035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention.

Conclusions: A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat.
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http://dx.doi.org/10.1111/eci.13548DOI Listing
August 2021

Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia.

Eur Respir J 2021 10 14;58(4). Epub 2021 Oct 14.

UCL Great Ormond Street Institute of Child Health, London, UK

Background: Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies.

Methods: We describe an immunofluorescence screening method, enabled by extensive expansion of basal cells from PCD patients and the directed differentiation of these cells into ciliated epithelium in miniaturised 96-well transwell format ALI cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the gene.

Results: Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures. The screening system in our proof-of-principal investigation allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. We observed restoration of basal body formation but not the generation of cilia in the patient's nasal epithelial cells CONCLUSION: Our study provides a platform for higher throughput analyses of airway epithelia that is applicable in a range of settings and suggests novel avenues for drug evaluation and development in PCD caused by nonsense mutations.
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http://dx.doi.org/10.1183/13993003.00455-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514977PMC
October 2021

Adiponectin and leptin exert antagonizing effects on proliferation and motility of papillary thyroid cancer cell lines.

J Physiol Biochem 2021 May 15;77(2):237-248. Epub 2021 Feb 15.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania, "Luigi Vanvitelli,", Via G. Vivaldi 42, 81100, Caserta, Italy.

Adiponectin (Acrp30) and leptin, adipokines produced and secreted mainly by the adipose tissue, are involved in human carcinogenesis. Thyroid carcinomas are frequent endocrine cancers, and several evidences suggest that they are correlated with obesity. In this study, we first analyzed the expression levels and prognostic values of Acrp30, leptin, and their receptors in thyroid cancer cells. Then, we investigated the role of Acrp30 and leptin in proliferation, migration, and invasion. We found that Acrp30 treatment alone inhibits cell proliferation and cell viability in a time and dose-dependent manner; leptin alone does not influence thyroid cancer cells (BCPAP and K1) proliferation, but the combined treatment reverts Acrp30-induced effects on cell proliferation. Additionally, through wound healing and Matrigel Matrix invasion assays, we unveiled that Acrp30 inhibits thyroid cancer cell motility, while leptin induces the opposite effect. Importantly, in the combined treatment, Acrp30 and leptin exert antagonizing effects on papillary thyroid cancer cells' migration and invasion in both BCPAP and K1 cell lines. Highlights of these studies suggest that Acrp30 and leptin could represent therapeutic targets and biomarkers for the management of thyroid cancer.
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http://dx.doi.org/10.1007/s13105-021-00789-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121733PMC
May 2021

Adiponectin in Cerebrospinal Fluid from Patients Affected by Multiple Sclerosis Is Correlated with the Progression and Severity of Disease.

Mol Neurobiol 2021 Jun 23;58(6):2663-2670. Epub 2021 Jan 23.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania, "Luigi Vanvitelli", Via G. Vivaldi 42, 81100, Caserta, Italy.

Adiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p < 0.001). Interestingly, CSF adiponectin positively correlated with CSF IgG, and CSF/serum albumin directly correlated with CSF/serum adiponectin. Our data demonstrated that CSF adiponectin predicts a worse prognosis: patients with the progressive form of MS had higher levels compared with the relapsing remitting form; patients with higher EDSS at baseline and a higher MS severity score at 4.5-year follow-up had significantly elevated adiponectin levels with respect to patients with a less severe phenotype. Finally, the adiponectin oligomerization profile was altered in CSF from MS patients, with a significant increase in HMW and MMW. The correlation of CSF adiponectin with the severity and prognosis of MS disease confirmed the role of this adipokine in the inflammatory/immune processes of MS and suggested its use as a complementary tool to assess the severity, progression and prognosis of the disease. Further studies on larger MS cohorts are needed to clarify the contribution of adiponectin to the etiopathogenesis of MS.
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http://dx.doi.org/10.1007/s12035-021-02287-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128828PMC
June 2021

Urtica dioica L. leaf chemical composition: A never-ending disclosure by means of HR-MS/MS techniques.

J Pharm Biomed Anal 2021 Feb 6;195:113892. Epub 2021 Jan 6.

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, I, 81100, Caserta, Italy.

The metabolite profiling of plant extracts always represents an exciting challenge, as the chemical diversity of natural products is still far beyond the researchers' imagination, even focusing on a plant that is thought to have already been broadly investigated. Herein UHPLC-HRMS/MS techniques were applied to an alcoholic crude extract from nettle leaves and proved to be a precious tool for the disclosure of secondary metabolites never found before. Hydroxycinnamic acid derivatives were the most representative constituents, with a 2-caffeoilisocitric acid cyclodimer described for the first time, besides four C-glycosylated flavones, bearing a 3-hydroxy-3-methylglutaryl function. This deep investigation paves the way for the isolation and full characterization of these molecules by means of spectroscopic techniques. Moreover, based on preliminary cytotoxicity evaluation, further research on the use of this nettle extract as a valuable nutraceutical product is encouraged.
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http://dx.doi.org/10.1016/j.jpba.2021.113892DOI Listing
February 2021

Case Report: Concurrent Resistance and Aerobic Training Regulate Adiponectin Expression and Disease Severity in Multiple Sclerosis: A Case Study.

Front Neurosci 2020 22;14:567302. Epub 2020 Dec 22.

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy.

Adapted exercise is an effective non-pharmacological tool to improve functional, cognitive, and psychological parameters in multiple sclerosis (MS), in association with increased quality of life (QoL) and decreased disease severity. Adipose tissue, through the production of different adipokines, is involved in regulating energy metabolism and inflammation. Adiponectin, increased in MS, circulates as oligomers of low (LMW), medium (MMW), and high molecular weight (HMW), the latter mediating the main biological effects. The aim of study was to evaluate the effects of 4 months training at moderate intensity [65% heart rate reserve (HRR)] on BMI, adiponectin, and QoL in a volunteer with secondary progressive MS. The parameters were evaluated before (T0), after 4 months training (T1), and 6 months after the end of training (T2); total serum adiponectin and its oligomeric profile were evaluated. We found a reduction in BMI (-0.9%) and FAT (-2.6%), an improvement in perceived QoL and a reduced expression of total adiponectin and HMW oligomers together with decreased MS disability level at T1 measured by EDSS. Despite the limitations of a case study, this represent a starting point to understand the influence of exercise in MS and the relationship with adiponectin expression.
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http://dx.doi.org/10.3389/fnins.2020.567302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783198PMC
December 2020

Metabolic Perturbations and Severe COVID-19 Disease: Implication of Molecular Pathways.

Int J Endocrinol 2020 28;2020:8896536. Epub 2020 Nov 28.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università Degli Studi Della Campania "Luigi Vanvitelli", Via G. Vivaldi 42, Caserta 81100, Italy.

Coronavirus disease (COVID-19) is caused by SARS-CoV-2 virus, which can result in serious respiratory illnesses such as pneumonia leading to respiratory failure. It was first reported in Wuhan, Hubei, China, in December 2019 and rapidly spread globally, becoming a pandemic in March 2020. Among comorbidities observed in SARS-CoV-2 positive patients, hypertension (68.3%) and type 2-diabetes (30.1%) are the most frequent conditions. Although symptoms are highly heterogeneous (ranging from absence of symptoms to severe acute respiratory failure), patients with metabolic-associated diseases often experience worse COVID-19 outcomes. This review investigates the association between metabolic disorders and COVID-19 severity, exploring the molecular mechanisms potentially underlying this relationship and those that are responsible for more severe COVID-19 outcomes. In addition, the role of the main biological processes that may connect metabolic alterations to SARS-CoV-2 infection such as hyperglycemia, immune system deregulation, ACE-2 receptor modulation, and inflammatory response is described. The impact of metabolic disorders on the prognosis of COVID-19 has major implications in public health especially for countries affected by a high incidence of metabolic diseases.
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http://dx.doi.org/10.1155/2020/8896536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703458PMC
November 2020

Adiponectin is Associated with Neutrophils to Lymphocyte Ratio in Patients with Chronic Obstructive Pulmonary Disease.

COPD 2021 02 11;18(1):70-75. Epub 2020 Dec 11.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Caserta, Italy.

Disproportionate systemic inflammation in chronic obstructive pulmonary disease (COPD) is associated with declining lung functions and comorbidities. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have emerged as valuable markers of the systemic inflammation in COPD. Adiponectin (Acpr30) circulates in serum as complexes of different molecular weight (HMW, MMW, LMW) with multifaceted metabolic and anti-inflammatory properties implicated in airway pathophysiology. We aimed to investigate the association between Acpr30 and its oligomers and the NLR and PLR in COPD patients. Seventy stable COPD patients were enrolled. Acrp30 serum levels and the HMW oligomers as well as hematological parameters and their ratio were evaluated. Both NLR and PLR are associated with lower BMI. Interestingly, total Acpr30 is negatively associated with NLR but not with PLR; after adjusting for age, BMI and FEV1, Acpr30 was independently associated with NLR. Conversely, HMW Acpr30 and HMW/Acpr30 ratio were positively correlated to NLR. The association of Acpr30, HMW Acpr30 and HMW/totalAcpr30 ratio with NLR but not with PLR in COPD patients indicates that Acrp30 oligomerization could represent a biological mechanism interfering with systemic inflammation in COPD. Further studies in larger cohorts of patients are required to confirm these results.
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http://dx.doi.org/10.1080/15412555.2020.1857718DOI Listing
February 2021

Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients.

Sci Rep 2020 12 8;10(1):21482. Epub 2020 Dec 8.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche (DISTABIF), Università della Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy.

Common variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder characterized by a high clinical and genetic heterogeneity. The molecular underlying causes of CVID are not still now clear and the delays in diagnosis and treatment worsen the prognosis of the patients. MicroRNAs are non-coding, endogenous small RNAs often deregulated in human diseases, such as autoimmune and other immune-based disorders. In the present study, we aimed to evaluate miRNAs associated with the CVID and, in particular, with the response to the first Ig replacement therapy. To this aim, we compared miRNA profile obtained by serum samples of treatment-naïve CVID patients before and 24 h after the first Ig replacement therapy. For the first time, using a microarray assay followed by an integrated bioinformatics/biostatistics analysis, we identified five microRNAs (hsa-miR-6742, hsa-miR-1825, hsa-miR-4769-3p, hsa-miR-1228-3p, hsa-miR-1972) differently modulated in CVID patients by Ig infusion. All of them were down-regulated, excepted miR-6742 which was up-regulated. The latter may be of particular interest, since its functions are related to pathways involving Class I MHC mediated antigen processing and adaptive as well as innate Immune System. In conclusion, this study shows for the first time the modulation of miRNAs involved in CVID patients after the first Ig replacement therapy. Further studies are needed to assess whether such miRNAs could represent novel potential biomarkers in management and therapy of CVID patients.
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http://dx.doi.org/10.1038/s41598-020-77100-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722869PMC
December 2020

Molecular mechanisms involved in the positive effects of physical activity on coping with COVID-19.

Eur J Appl Physiol 2020 Dec 3;120(12):2569-2582. Epub 2020 Sep 3.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", Via A. Vivaldi, 81100, Caserta, Italy.

Purpose: Physical activity (PA) represents the first line of defence against diseases characterised by increased inflammation status, such as metabolic and infectious diseases. Conversely, a sedentary lifestyle-associated with obesity, type 2 diabetes and cardiovascular disorders-negatively impacts on general health status, including susceptibility to infections. At a time of a pandemic SARS-CoV2 infection, and in the context of the multiorgan crosstalk (widely accepted as a mechanism participating in the pathophysiology of all organs and systems), we examine the complex interplay mediated by skeletal muscle contraction involving the immune system and how this contributes to control health status and to counteract viral infections. In so doing, we review the molecular mechanisms and expression of molecules modulated by PA, able to provide the proper molecular equipment against viral infections such as the current SARS-CoV2.

Methods: A critical review of the literature was performed to elucidate the molecular mechanisms and mediators induced by PA that potentially impact on viral infections such as SARS-CoV2.

Results: We showed the effects mediated by regular moderate PA on viral adverse effects through the regulation of biological processes involving the crosstalk between skeletal muscle, the immune system and adipose tissue. Evidence was provided of the effects mediated by modulation of the expression of inflammation markers.

Conclusion: A tigth association between PA and reduction in inflammation status allows effective counteracting of SARS-CoV2 infection. It is therefore essential to persuade people to keep active.
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http://dx.doi.org/10.1007/s00421-020-04484-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471545PMC
December 2020

The State of Art of Regenerative Therapy in Cardiovascular Ischemic Disease: Biology, Signaling Pathways, and Epigenetics of Endothelial Progenitor Cells.

Cells 2020 08 11;9(8). Epub 2020 Aug 11.

Dipartimento di Medicina e Scienze della Salute "V.Tiberio", Università del Molise, 86100 Campobasso, Italy.

Ischemic heart disease is currently a major cause of mortality and morbidity worldwide. Nevertheless, the actual therapeutic scenario does not target myocardial cell regeneration and consequently, the progression toward the late stage of chronic heart failure is common. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that contribute to the homeostasis of the endothelial wall in acute and chronic ischemic disease. Calcium modulation and other molecular pathways (NOTCH, VEGFR, and CXCR4) contribute to EPC proliferation and differentiation. The present review provides a summary of EPC biology with a particular focus on the regulatory pathways of EPCs and describes promising applications for cardiovascular cell therapy.
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http://dx.doi.org/10.3390/cells9081886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465688PMC
August 2020

Impact of Physical Activity on Cognitive Functions: A New Field for Research and Management of Cystic Fibrosis.

Diagnostics (Basel) 2020 Jul 18;10(7). Epub 2020 Jul 18.

CEINGE Biotecnologie Avanzate SCarl, Via Gaetano Salvatore 486, 80145 Napoli, Italy.

Cystic Fibrosis (CF) is a genetic disease inherited by an autosomal recessive mechanism and characterized by a progressive and severe multi-organ failure. Mutations in Cystic Fibrosis Conductance Regulator (CFTR) protein cause duct obstructions from dense mucus secretions and chronic inflammation related to organ damage. The progression of the disease is characterized by a decline of lung function associated with metabolic disorders and malnutrition, musculoskeletal disorders and thoracic deformities, leading to a progressive decrement of the individual's quality of life. The World Health Organization (WHO) qualifies Physical Activity (PA) as a structured activity produced by skeletal muscles' movements that requires energy consumption. In the last decade, the number of studies on PA increased considerably, including those investigating the effects of exercise on cognitive and brain health and mental performance. PA is recommended in CF management guidelines, since it improves clinic outcomes, such as peripheral neuropathy, oxygen uptake peak, bone health, glycemic control and respiratory functions. Several studies regarding the positive effects of exercise in patients with Cystic Fibrosis were carried out, but the link between the effects of exercise and cognitive and brain health in CF remains unclear. Animal models showed that exercise might improve learning and memory through structural changes of brain architecture, and such a causal relationship can also be described in humans. Indeed, both morphological and environmental factors seem to be involved in exercise-induced neural plasticity. An increase of gray matter volume in specific areas is detectable as a consequence of regular training in humans. Neurobiological processes associated with brain function improvements include biochemical modifications, such as neuromodulator or neurohormone release, brain-derived neurotrophic factor (BDNF) production and synaptic activity changes. From a functional point of view, PA also seems to be an environmental factor enhancing cognitive abilities, such as executive functions, memory and processing speed. This review describes the current state of research regarding the impacts of physical activity and exercise on cognitive functions, introducing a possible novel field of research for optimizing the management of Cystic Fibrosis.
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http://dx.doi.org/10.3390/diagnostics10070489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400241PMC
July 2020

Adiponectin Is Inversely Associated With Tumour Grade in Colorectal Cancer Patients.

Anticancer Res 2020 Jul;40(7):3751-3757

Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania, "Luigi Vanvitelli", Naples, Italy

Background/aim: Colorectal cancer is frequently associated with metabolic diseases. Adiponectin (APN) is an insulin-sensitizing adipokine circulating as low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers; the latter are the most bio-active oligomers. APN, through AdipoR1, AdipoR2 and T-cadherin receptors, regulates inflammation, and proliferation. Considering the anti-proliferative and anti-inflammatory properties of APN, we investigated the involvement of the "APN system" in colorectal cancer.

Materials And Methods: A total of 44 colorectal cancer patients and 51 healthy controls were recruited. We analysed APN and HMW oligomers in sera, AdipoR1, AdipoR2 and T-cadherin expression in non-cancerous and cancerous colon tissues.

Results: we found statistically lower levels of APN in patients compared to controls, with a specific decrease of HMW oligomers. Importantly, APN correlated to cancer grade. AdipoR1 was found overexpressed in cancerous compared to non-cancerous tissues while AdipoR2 and T-cadherin were down-regulated.

Conclusion: The deregulated expression of the "APN system" in colorectal cancer with a specific correlation to tumor grade suggests APN as a promising biomarker in colorectal cancer.
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http://dx.doi.org/10.21873/anticanres.14364DOI Listing
July 2020

Implications of the Adiponectin System in Non-Small Cell Lung Cancer Patients: A Case-Control Study.

Biomolecules 2020 06 18;10(6). Epub 2020 Jun 18.

Department of Translational Medical Sciences, University of Campania "L. Vanvitelli", 80131 Naples, Italy.

Alterations of adipose tissue occurring in obesity have been recognized as a major risk factor for several cancers. The relationship between adipose tissue and lung cancer, which is the main cancer-related cause of death worldwide, still requires investigation. Perturbations in the adipokine system are likely to interfere with inter-organ crosstalk in lung cancer, which may influence the lung tumor microenvironment. Adiponectin (Acrp30) expression is deregulated in several cancer types. Acrp30 circulates as oligomers with a Low (LMW), Medium (MMW), and High Molecular Weight (HMW), with the latter mediating the main biological effects. Acrp30 acts through AdipoR1 and AdipoR2 receptors. T-cadherin has been described as a non-signaling receptor. This study's aim was to investigate the regulation of serum Acrp30 and its receptors in sample tissue from non-small cell lung cancer (NSCLC) patients. We recruited 72 NSCLC patients and 60 healthy controls, whom we evaluated in terms of their Acpr30 levels and oligomeric profile. In addition, the expression of AdipoRs in tissues from lung cancer specimens was also measured and compared to coupled healthy lung samples. Our findings show a significant reduction of total Acrp30 levels in NSCLC patients compared to normal subjects, with a specific down-regulation of HMW oligomers. Acrp30 expression was lower in lung adenocarcinoma than other subtypes, regardless of other factors. A significantly higher expression of AdipoR1 was observed, while no differences in R2 and a lower expression of T-cadherin were found in lung cancer specimens compared to normal healthy lung tissues. Involvement of the Acrp30 system in lung cancer may provide new insight into the interaction between adipose tissue and lung and sheds light on its potential ability to influence the lung tumor microenvironment.
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http://dx.doi.org/10.3390/biom10060926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356727PMC
June 2020

AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells.

J Oncol 2020 22;2020:7262479. Epub 2020 Jan 22.

Dipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Via L. De Crecchio 7, Naples 80138, Italy.

AdipoRon (AdipoR) is the first synthetic molecule acting as a selective and potent adiponectin receptor agonist. Recently, the possible pharmacological use of AdipoR in different pathological conditions has been addressed. Interestingly, initial evidence suggests that AdipoR may have anticancer properties in different preclinical models, such as pancreatic and ovarian cancer. To our knowledge, so far no research has been directed at determining the impact of AdipoR on osteosarcoma, the most aggressive and metastatic bone malignancy occurring in childhood and adolescence age. Here, we investigate the possible antitumor effects of AdipoR in osteosarcoma cell lines. MTT and cell growth curve assays clearly indicate that AdipoR inhibits, at different extents, proliferation in both U2OS and Saos-2 osteosarcoma cell lines, the latter being more sensitive. Moreover, flow cytometry-based assays point out a significant G0/G1 phase accumulation and a contemporary S phase decrease in response to AdipoR. Consistent with the different sensitivity, a strong subG1 appearance in Saos-2 after 48 and 72 hours of treatment is also observed. The investigation of the molecular mechanisms highlights a common and initial ERK1/2 activation in response to AdipoR in both Saos-2 and U2OS cells. Interestingly, a simultaneous and dramatic downregulation of p70S6K phosphorylation, one of the main targets of mTORC1 pathway, has also been observed in AdipoR-treated Saos-2, but not in U2OS cells. Importantly, a strengthening of AdipoR-induced effects was reported upon everolimus-mediated mTORC1 perturbation in U2OS cells. In conclusion, our findings provide initial evidence of AdipoR as an anticancer molecule differently affecting various signaling pathways involved in cell cycle and cell death in osteosarcoma cells and encourage the design of future studies to further understand its pattern of activities.
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http://dx.doi.org/10.1155/2020/7262479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204133PMC
January 2020

The Important Role of Adiponectin and Orexin-A, Two Key Proteins Improving Healthy Status: Focus on Physical Activity.

Front Physiol 2020 22;11:356. Epub 2020 Apr 22.

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

Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.
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http://dx.doi.org/10.3389/fphys.2020.00356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188914PMC
April 2020

Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States.

Int J Mol Sci 2020 May 2;21(9). Epub 2020 May 2.

Dipartimento di Medicina Clinica e Sperimentale, Università di Foggia, 71100 Foggia, Italy.

Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases.
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http://dx.doi.org/10.3390/ijms21093228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246656PMC
May 2020
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