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State-of-the-Art Molecular Endocrinology and Metabolism in Italy
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State-of-the-Art Molecular Endocrinology and Metabolism in Italy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 21424

Special Issue Editors

Prof. Dr. Rosario Scaglione

E-Mail Website
Guest Editor
Università degli Studi di Palermo | UNIPA · Department of internal medicine and medical specialties (DIMIS)
Interests: Hypertension Cardiovascular Risk Clinical Cardiology Risk Prediction Metabolic Diseases Internal Medicine Inflammatory Biomarkers Abdominal Obesity Atrial Fibrillation
Prof. Dr. Rossella Elisei

E-Mail Website
Guest Editor
Azienda Ospedaliero Universitaria Pisana
Interests: Cancer Biology; Clinical Oncology; Cancer Diagnostics
Prof. Dr. Piero Marchetti

E-Mail Website
Guest Editor
University of Pisa, Cisanello Hospital, via Paradisa 2, 56100, Pisa, Italy
Interests: beta cell; diabetes; insulin secretion; pancreas; islet

Special Issue Information

Dear Colleagues,

This Special Issue aims to provide an up-to-date and comprehensive view on the state-of-the-art of endocrinology and metabolism in Italy.

Based on long-term traditions of fundamental science in Italy, we would like to provide a comprehensive insight into the state-of-the-art of research activities in the country. All kinds of arcticles are welcome, including contributions about original investigations, as well as reviews in the field. The covered topics of interest include, but are not limited to, the following:

  • Endocrine systems and endocrine-related diseases;
  • Molecular, cellular, genetic, epigenetic, developmental approaches, and animal models;
  • Novel insights into physiology, pathophysiology, and therapeutics;
  • Neuroendocrinology and neuroendocrine control of endocrine axes;
  • Classical glands (thyroid, adrenal, pituitary, parathyroid, testis, ovary, pituitary, etc.) and other endocrine systems: gut, bone, liver, etc.;
  • Lipids and bone metabolism;
  • Hormones, paracrine factors, receptors and binding components, nuclear receptors membrane receptors, signal transduction pathway;
  • Steroid biosynthetic enzymes, metabolism of hormones, neurotransmitters, etc.;
  • Cellular interactions and factors involved;
  • Energy expenditure;
  • Diabetes;
  • Infertility and reproductive diseases;
  • Obesity;
  • Osteoporosis;
  • Aging;
  • Endocrine-related tumor and cancer;
  • Endocrine disruption;
  • Cross-disciplinary and integrative studies;
  • Comparative aspects of endocrinology.

Prof. Dr. Rosario Scaglione
Prof. Dr. Rossella Elisei
Prof. Dr. Piero Marchetti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (6 papers)

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Research

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12 pages, 449 KiB  
Article
Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors
by Chiara Verdelli, Silvia Carrara, Riccardo Maggiore, Paolo Dalino Ciaramella and Sabrina Corbetta
Int. J. Mol. Sci. 2024, 25(19), 10782; https://doi.org/10.3390/ijms251910782 - 7 Oct 2024
Viewed by 361
Abstract
The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd [...] Read more.
The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
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11 pages, 283 KiB  
Article
A Multigene-Panel Study Identifies Single Nucleotide Polymorphisms Associated with Prostate Cancer Risk
by Maria Antonietta Manca, Fabio Scarpa, Davide Cossu, Elena Rita Simula, Daria Sanna, Stefano Ruberto, Marta Noli, Hajra Ashraf, Tatiana Solinas, Massimo Madonia, Roberto Cusano and Leonardo A. Sechi
Int. J. Mol. Sci. 2023, 24(8), 7594; https://doi.org/10.3390/ijms24087594 - 20 Apr 2023
Cited by 2 | Viewed by 1431
Abstract
The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in [...] Read more.
The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in immune responses and prostate cancer risk. Thirty-five genes were analyzed in 47 patients with prostate cancer and 43 healthy controls using next-generation sequencing. Allelic and genotype frequencies were calculated in both cohorts, and a generalized linear mixed model was applied to test the relationship between prostate cancer risk and nucleotide substitution. Odds ratios were calculated to describe the association between each single nucleotide polymorphism (SNP) and prostate cancer risk. Significant changes in allelic and genotypic distributions were observed for IL4R, IL12RB1, IL12RB2, IL6, TMPRSS2, and ACE2. Furthermore, a generalized linear mixed model identified statistically significant associations between prostate cancer risk and SNPs in IL12RB2, IL13, IL17A, IL4R, MAPT, and TFNRS1B. Finally, a statistically significant association was observed between IL2RA and TNFRSF1B and Gleason scores, and between SLC11A1, TNFRSF1B and PSA values. We identified SNPs in inflammation and two prostate cancer-associated genes. Our results provide new insights into the immunogenetic landscape of prostate cancer and the impact that SNPs on immune genes may have on affecting the susceptibility to prostate cancer. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
13 pages, 1432 KiB  
Article
Incretin Response to Mixed Meal Challenge in Active Cushing’s Disease and after Pasireotide Therapy
by Mattia Barbot, Alessandro Mondin, Daniela Regazzo, Valentina Guarnotta, Daniela Basso, Carla Giordano, Carla Scaroni and Filippo Ceccato
Int. J. Mol. Sci. 2022, 23(9), 5217; https://doi.org/10.3390/ijms23095217 - 6 May 2022
Cited by 2 | Viewed by 2126
Abstract
Cushing’s disease (CD) causes diabetes mellitus (DM) through different mechanisms in a significant proportion of patients. Glucose metabolism has rarely been assessed with appropriate testing in CD; we aimed to evaluate hormonal response to a mixed meal tolerance test (MMTT) in CD patients [...] Read more.
Cushing’s disease (CD) causes diabetes mellitus (DM) through different mechanisms in a significant proportion of patients. Glucose metabolism has rarely been assessed with appropriate testing in CD; we aimed to evaluate hormonal response to a mixed meal tolerance test (MMTT) in CD patients and analyzed the effect of pasireotide (PAS) on glucose homeostasis. To assess gastro-entero-pancreatic hormones response in diabetic (DM+) and non-diabetic (DM–) patients, 26 patients with CD underwent an MMTT. Ten patients were submitted to a second MMTT after two months of PAS 600 µg twice daily. The DM+ group had significantly higher BMI, waist circumference, glycemia, HbA1c, ACTH levels and insulin resistance indexes than DM− (p < 0.05). Moreover, DM+ patients exhibited increased C-peptide (p = 0.004) and glucose area under the curve (AUC) (p = 0.021) during MMTT, with a blunted insulinotropic peptide (GIP) response (p = 0.035). Glucagon levels were similar in both groups, showing a quick rise after meals. No difference in estimated insulin secretion and insulin:glucagon ratio was found. After two months, PAS induced an increase in both fasting glycemia and HbA1c compared to baseline (p < 0.05). However, this glucose trend after meal did not worsen despite the blunted insulin and C-peptide response to MMTT. After PAS treatment, patients exhibited reduced insulin secretion (p = 0.005) and resistance (p = 0.007) indexes. Conversely, glucagon did not change with a consequent impairment of insulin:glucagon ratio (p = 0.009). No significant differences were observed in incretins basal and meal-induced levels. Insulin resistance confirmed its pivotal role in glucocorticoid-induced DM. A blunted GIP response to MMTT in the DM+ group might suggest a potential inhibitory role of hypercortisolism on enteropancreatic axis. As expected, PAS reduced insulin secretion but also induced an improvement in insulin sensitivity as a result of cortisol reduction. No differences in incretin response to MMTT were recorded during PAS therapy. The discrepancy between insulin and glucagon trends while on PAS may be an important pathophysiological mechanism in this iatrogenic DM; hence restoring insulin:glucagon ratio by either enhancing insulin secretion or reducing glucagon tone can be a potential therapeutic target. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
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Review

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16 pages, 1090 KiB  
Review
Cardiomyocyte Damage: Ferroptosis Relation to Ischemia-Reperfusion Injury and Future Treatment Options
by Jolanta Laukaitiene, Greta Gujyte and Edmundas Kadusevicius
Int. J. Mol. Sci. 2023, 24(16), 12846; https://doi.org/10.3390/ijms241612846 - 16 Aug 2023
Cited by 1 | Viewed by 1889
Abstract
About half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that “time is muscle”, which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes [...] Read more.
About half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that “time is muscle”, which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes of the ischemic myocardium. As the latest studies show, metabolic changes after acute myocardial infarction (AMI) are inconsistent and depend on many constituents, which leads to many limitations and lack of unification. Nevertheless, one of the promising novel mechanistic approaches related to iron metabolism now plays an invaluable role in the ischemic heart research field. The heart, because of its high levels of oxygen consumption, is one of the most susceptible organs to iron-induced damage. In the past few years, a relatively new form of programmed cell death, called ferroptosis, has been gaining much attention in the context of myocardial infarction. This review will try to summarize the main novel metabolic pathways and show the pivotal limitations of the affected myocardium metabolomics. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
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13 pages, 305 KiB  
Review
Neglected Facts on Mycobacterium Avium Subspecies Paratuberculosis and Type 1 Diabetes
by Veronika Ozana, Karel Hruska and Leonardo A. Sechi
Int. J. Mol. Sci. 2022, 23(7), 3657; https://doi.org/10.3390/ijms23073657 - 26 Mar 2022
Cited by 8 | Viewed by 2933
Abstract
Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization, lifestyle changes and new technologies in the animal and plant industry are involved in frequent contact of people with mycobacteria. [...] Read more.
Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization, lifestyle changes and new technologies in the animal and plant industry are involved in frequent contact of people with mycobacteria. Type 1 diabetes is a multifactorial polygenic disease; its origin is conditioned by the mutual interaction of genetic and other factors. The environmental factors and certain pathogenetic pathways are shared by some immune mediated chronic inflammatory and autoimmune diseases, which are associated with triggers originating mainly from Mycobacterium avium subspecies paratuberculosis, an intestinal pathogen which persists in the environment. Type 1 diabetes and some other chronic inflammatory diseases thus pose the global health problem which could be mitigated by measures aimed to decrease the human exposure to this neglected zoonotic mycobacterium. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
21 pages, 691 KiB  
Review
The Role of Testosterone in the Elderly: What Do We Know?
by Biagio Barone, Luigi Napolitano, Marco Abate, Luigi Cirillo, Pasquale Reccia, Francesco Passaro, Carmine Turco, Simone Morra, Francesco Mastrangelo, Antonio Scarpato, Ugo Amicuzi, Vincenzo Morgera, Lorenzo Romano, Francesco Paolo Calace, Savio Domenico Pandolfo, Luigi De Luca, Achille Aveta, Enrico Sicignano, Massimiliano Trivellato, Gianluca Spena, Carlo D’Alterio, Giovanni Maria Fusco, Raffaele Vitale, Davide Arcaniolo and Felice Crocettoadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(7), 3535; https://doi.org/10.3390/ijms23073535 - 24 Mar 2022
Cited by 46 | Viewed by 11923
Abstract
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, [...] Read more.
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Endocrinology and Metabolism in Italy)
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