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Molecular diagnosis relieves patients of uncertainty, aids informed decisions about health and reproductive choices, and helps them join clinical trials or access available therapy. Genetic testing by next generation sequencing (NGS) is the suggested choice for a wide variety of disorders with heterogeneous phenotypes, alleles and loci. The development of a NGS service at MAGI Balkans, through the support of a partner, increases the availability of forefront genetic testing in Albania with great advantages for patients and their families. Here we report the NGS tests performed in collaboration with MAGI Euregio, Italy, for the diagnosis of rare genetic disease in seven probands and their families. The diseases/manifestations included ichthyosis, familial adenomatous polyposis, diabetes, syndromic craniosynostosis, fronto-temporal dementia, fragile X syndrome and ataxia. We obtained an overall detection rate of 57%. For 4/7 probands we identified a pathogenic or likely pathogenic variant, while for the others, the results did not completely explain the phenotype. All variants were confirmed by Sanger sequencing. Segregation of the variant with the affected phenotype was also evaluated.

The recent COVID-19 pandemic caused by SARS-CoV-2 affected hundreds of millions of people and caused millions of deaths. There are few effective medications against SARS-CoV-2, and several studies attempted to make drugs based on natural components, such as olive leaves. Olive leaves are rich in polyphenolic compounds, which were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. Polyphenols have renown anti-inflammatory and multitarget antiviral effects on several virus families, which could be among the reasons of the beneficial effects of the Mediterranean diet against COVID-19. This scoping review is focused on the effect of olive tree polyphenols as a natural remedy to inhibit SARS-CoV-2, mainly discussing their influence on the process of viral entry into host cells by endocytosis. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a leading cause of death worldwide, associated with poor prognosis outcomes and late treatment interventions. The pathological nature and extreme tissue heterogeneity of this disease has hampered all efforts to correctly diagnose and treat it. Omics sciences and precision medicine have revolutionized our understanding of pancreatic cancer, providing a new hope for patients suffering from this devastating disease. By analyzing large-scale biological data sets and developing personalized treatment strategies, researchers and clinicians are working together to improve patient outcomes and ultimately find a cure for pancreatic cancer. [ABSTRACT FROM AUTHOR]

In the last decade, renal carcinoma has become more prevalent in European and North American regions. Kidney tumors are usually categorized based on histological features, with renal cell carcinoma being the most common subtype in adults. Despite conventional diagnostic and therapeutic strategies, a rise in cancer incidence and recurrence necessitates a fresh approach to diagnosing and treating kidney cancer. This review focuses on novel multi-omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, and microbiomics, to better understand the molecular and clinical features of renal cell carcinoma. Studies integrating omics sciences have shown early promise in enhancing prognostic and therapeutic outcomes for various kidney cancer subtypes and providing insight into fundamental pathophysiological mechanisms occurring at different molecular levels. This review highlights the importance of utilizing omics sciences as a revolutionary concept in diagnostics and therapeutics and the clinical implications of renal cell carcinoma. Finally, the review presents the most recent findings from large-scale multi-omics studies on renal cell carcinoma and its associations with patient subtyping and drug development. [ABSTRACT FROM AUTHOR]

Background. This article provides an overview of the application of omics sciences in melanoma research. The name omics sciences refers to the large-scale analysis of biological molecules like DNA, RNA, proteins, and metabolites. Methods. In the course of this review, we have adopted a focused research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources. Results. With the advent of high-throughput technologies, omics have become an essential tool for understanding the complexity of melanoma. In this article, we discuss the different omics approaches used in melanoma research, including genomics, transcriptomics, proteomics, and metabolomics. We also highlight the major findings and insights gained from these studies, including the identification of new therapeutic targets and the development of biomarkers for diagnosis and prognosis. Finally, we discuss the challenges and future directions in omics-based melanoma research, including the integration of multiple omics data and the development of personalized medicine approaches. Conclusions. Overall, this article emphasizes the importance of omics science in advancing our understanding of melanoma and its potential for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background. Thyroid cancer, a heterogeneous disease originating from the thyroid gland, stands as the predominant endocrine malignancy worldwide. Despite advances in diagnosis and treatment, some patients still experience recurrence and mortality, which highlights the need for more personalized approaches to treatment. Omics sciences, encompassing genomics, transcriptomics, proteomics, and metabolomics, offer a high-throughput and impartial methodology for investigating the molecular signatures of thyroid cancer. Methods. In the course of this review, we have adopted a focused research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources. Results. These techniques enable the identification of molecular markers that can aid in diagnosis, prognosis, and treatment selection. As an illustration, through genomics studies, numerous genetic alterations commonly discovered in thyroid cancer have been identified, such as mutations in the BRAF and RAS genes. Through transcriptomics studies, distinctively expressed genes in thyroid cancer have been uncovered, playing roles in diverse biological processes, including cell proliferation, invasion, and metastasis. These genes can serve as potential targets for novel therapies. Proteomics studies have unveiled differentially expressed proteins intricately involved in thyroid cancer pathogenesis, presenting promising biomarkers for early detection and disease progression monitoring. Metabolomics studies have identified alterations in metabolic pathways linked to thyroid cancer, offering promising avenues for potential therapeutic targets. Conclusions. Precision medicine in thyroid cancer involves the integration of omics sciences with clinical data to develop personalized treatment plans for patients. Employing targeted therapies guided by molecular markers has exhibited promising outcomes in enhancing the prognosis of thyroid cancer patients. Notably, those with advanced thyroid cancer carrying BRAF mutations have displayed substantial responses to specific targeted therapies, such as vemurafenib and dabrafenib. [ABSTRACT FROM AUTHOR]

Background. Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is testicular cancer, accounting for 1% to 2% of all cancers in men. Methods. Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources. Results. The onset and spread of testicular cancer are significantly influenced by genetic changes, including mutations in oncogenes, tumor suppressor genes, and DNA repair genes. As a result of identifying these specific genetic mutations in cancers, targeted medications have been developed to disrupt the signaling pathways affected by these genetic changes. To improve the diagnosis and treatment of this disease, it is crucial to understand its natural and clinical histories. Conclusions. In order to comprehend cancer better and to discover new biomarkers and therapeutic targets, oncologists are increasingly employing omics methods, such as genomics, transcriptomics, proteomics, and metabolomics. Targeted medications that focus on specific genetic pathways and mutations hold promise for advancing the diagnosis and management of this disease. [ABSTRACT FROM AUTHOR]

This comprehensive review explores the potential of omics sciences--such as genomics, transcriptomics, proteomics, and metabolomics--in advancing the diagnosis and therapy of urothelial carcinoma (UC), a prevalent and heterogeneous cancer affecting the urinary tract. The article emphasizes the significant advancements in understanding the molecular mechanisms underlying UC development and progression, obtained through the application of omics approaches. Genomic studies have identified recurrent genetic alterations in UC, while transcriptomic analyses have revealed distinct gene expression profiles associated with different UC subtypes. Proteomic investigations have recognized protein biomarkers with diagnostic and prognostic potential, and metabolomic profiling has found metabolic alterations that are specific to UC. The integration of multi-omics data holds promises in refining UC subtyping, identifying therapeutic targets, and predicting treatment response. However, challenges like the standardization of omics technologies, validation of biomarkers, and ethical considerations need to be addressed to successfully translate these findings into clinical practice. Omics sciences offer tremendous potential in revolutionizing the diagnosis and therapy of UC, enabling more precise diagnostic methods, prognostic evaluations, and personalized treatment selection for UC patients. Future research efforts should focus on overcoming these challenges and translating omics discoveries into meaningful clinical applications to improve outcomes for UC patients. [ABSTRACT FROM AUTHOR]

Primary lymphedema (PLE) is a chronic disease caused by lymphatic dysplasia and progresses to irreversible tissue edema and hypertrophy. Understanding of PLE has been hitherto limited. The aim of this study is to devise an updated classification system for PLE of 1013 patients with PLE of lower limb were enrolled. Sex, age of onset, location, family history and morbidity were documented. The lymphatic imaging findings of magnetic resonance lymphography (MRL), indocyanine green lymphography (ICGL) and lymphoscintigraphy (LSG), skin tissue immunohistochemical staining, whole exome sequencing and the correlation of genotype-phenotype were evaluated. Patients were divided into a congenital onset category and a late onset category. The late onset category was further divided according to developmental age. The ratio of congenital-onset to late-onset PLE was 1:4 and that the highest incidence was in adolescence. The sex ratio was 1.04:1 and 1.5:1 in congenital-onset and late-onset groups, respectively. Three major lymphatic anomalies were identified, in which segmental lymphatic dysfunction, characterized by delayed or partial demonstration of lymph vessels, is the most common and associated with FLT4, GJC2, CELSR1, and PTPN14 mutations. The next most common type is lymphatic hyperplasia, which is associated with FOXC2 and GATA2 variants, followed by initial lymphatic aplasia or dysfunction, which is more common in patients with congenital PLE and associated with FLT4 mutation. A functional and structural combined classification of lymphatic anomalies is proposed, which includes segmental lymphatic dysfunction, lymphatic hyperplasia and initial lymphatic aplasia or dysfunction. [ABSTRACT FROM AUTHOR]

Adipocytes express various enzymes, such as aldo-keto reductases (AKR1C), 11β-hydroxysteroid dehydrogenase (11β-HSD), aromatase, 5α-reductases, 3β-HSD, and 17β-HSDs involved in steroid hormone metabolism in adipose tissues. Increased activity of AKR1C enzymes and their expression in mature adipocytes might indicate the association of these enzymes with subcutaneous adipose tissue deposition. The inactivation of androgens by AKR1C enzymes increases adipogenesis and fat mass, particularly subcutaneous fat. AKR1C also causes reduction of estrone, a weak estrogen, to produce 17β-estradiol, a potent estrogen and, in addition, it plays a role in progesterone metabolism. Functional impairments of adipose tissue and imbalance of steroid biosynthesis could lead to metabolic disturbances. In this review, we will focus on the enzymes involved in steroid metabolism and fat tissue deposition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Lymphedema is a debilitating disease and may be a comorbidity of obesity. New molecules have been investigated for the treatment of lymphedema; one of the most promising molecules is hydroxytyrosol. The aim of this study was to evaluate the association between mutations in genes mutated in lymphedema and the presence of obesity and making an estimate of the quality of life in lymphedema patients. MATERIALS AND METHODS: We recruited 71 Caucasian individuals with the diagnosis of primary lymphedema, and they undertook a questionnaire to assess their quality life. For this purpose, we developed a NGS custom-made panel comprising genes associated with lymphedema. RESULTS: An obesity rate of 20% was detected. The average Lymph-ICF-LL value for patients who consume olive oil daily was 20 with a better quality of life. Twenty-three patients resulted positive to the genetic test. Genetic variants with a likely association with obesity have been identified in PROX1, FOXC2 and FLT4. CONCLUSIONS: A obesity rate, higher than that reported by ISTAT, was detected. The use of olive oil enhances the quality of life of lymphedema patients. Moreover, a diagnostic approach by a NGS panel shows an association of lymphedema with obesity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate patient characteristics and factors that increase the risk of being admitted to intensive care and that influence survival in cases of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: One-hundred and ninety-one SARS-CoV-2 patients were admitted to the “Fondazione Poliambulanza di Brescia” Hospital (Brescia, Lombardy, Italy) in the period 1st March 2020 to 11th April 2020. Data on demographics, clinical presentation at admission, co-morbidities, pharmacological treatment, admission to intensive care and death was recorded. Logistic regression and survival analysis were carried out to investigate the risk of being admitted to intensive care and the risk of death. RESULTS: The mean age of the study cohort was 64.6±9.9 years (range 20-88). Median BMI was 28.5±5 kg/m². Fever (81%) and dyspnea (65%) were the most common symptoms on admission. Most of patients (63%) had at least one co-existing disease. The 157 (82%) patients admitted to intensive care were more likely to be of intermediate age (60-69 years; OR 3.23, 95% CI 1.32-8.38), overweight (OR 2.66, 95% CI 1.02- 7.07) or obese (OR 5.63, 95% CI 1.73-21.09) and with lymphocytopenia (OR 2.75, 95% CI 1.17- 6.89) than the 34 patients admitted to the ordinary ward. During intensive care, 50% of patients died and their death was associated with older age (HR 2.06, 95% CI 1.07-3.97), obesity (HR 2.23, 95% CI 1.15-4.35) and male gender (HR 1.9, 95% CI 1.02-3.57). CONCLUSIONS: We found that admission to intensive care and poor survival were associated with advanced age and higher body mass index, albeit with differences in statistical significance. Pre-existing diseases and symptoms on admission were not associated with different clinical outcomes. Interestingly, male gender was more prevalent among SARS-CoV-2 patients and was related negatively to survival, but it was not associated with more frequent admission to intensive care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Familial atrial fibrillation (FAF), a not uncommon arrhythmia of the atrium, is characterized by heritability, early onset and absence of other heart defects. The molecular and genetic basis is still not completely clear and genetic diagnosis cannot be achieved in about 90% of patients. In this study, we present the results of genetic screening by next generation sequencing in affected Russian families. PATIENTS AND METHODS: Sixty subjects (18 probands and 42 relatives) with a clinical diagnosis of FAF were enrolled in the study. Since AF frequently associates with other cardiomyopathies, we included all genes that were known to be associated with these disorders at the time of our study. All probands were therefore systematically screened for 47 genes selected from the literature. RESULTS: Our study revealed that seven variants co-segregated with the clinical phenotype in seven families. Interestingly, four out of six genes and three out of seven variants have already been associated with Brugada syndrome in the literature. CONCLUSIONS: To our knowledge, this is the first report of association of the CACNA1C, CTNNA3, PKP2, ANK2 and SCN10A genes with FAF; it is also the first study in Russian families. [ABSTRACT FROM AUTHOR]

Primary lymphedema is a rare inherited condition characterized by swelling of body tissues caused by accumulation of fluid, especially in the lower limbs. In many patients, primary lymphedema has been associated with variations in a number of genes involved in the development and maintenance of the lymphatic system. In this study, we performed a genetic screening in patients affected by primary lymphedema using a next generation sequencing (NGS) approach. With this technology, based on a custom-made oligonucleotide probe library, we were able to analyze simultaneously in each patient all the coding exons of 10 genes (FLT4, FOXC2, CCBE1, GJC2, MET, HGF, GATA2, SOX18, VEGFC, KIF11) associated with primary lymphedema. In the study population, composed of 45 familial and 71 sporadic cases, we identified the presence of rare variants with a potential pathogenic effect in 33% of subjects. Overall, we found a total of 36 different rare nucleotidic alterations, 30 of which had not been previously described. Among these, we identified 23 mutations that we considered most likely to be disease causing. Patients with an FLT4 or FOXC2 alteration accounted for the largest percentage of the sample, followed by MET, HGF, KIK11, GJC2 and GATA2. No alterations were identified in SOX18, VEGFC, and CCBE1 genes. In conclusion, we showed that NGS technology can be successfully applied to perform molecular screening of lymphedemaassociated genes in large cohort of patients with a reasonable effort in terms of cost, work, and time. [ABSTRACT FROM AUTHOR]

Emberger syndrome, or primary lymphedema with myelodysplasia, is a severe rare disease characterized by early primary lymphedema and blood anomalies including acute childhood leukemia. The syndrome is associated with heterozygous mutations in the GATA2 gene. We report on a 13-year-old boy who developed lymphedema of the right lower limb at age 6 years which was accompanied by severe panleukopenia and repeated episodes of erysipelas. The suspicion of Emberger syndrome was confirmed by detection of a new germinal line GATA2 mutation c.414_417del, p.Ser139Cysfs*78. Clinical treatment included a bone marrow transplant from the father. This case is one of a very limited number of Emberger syndrome cases documented in the literature, and genetic testing proved fundamental for definition of the condition and its association with a de novo mutation in the GATA2 which is reported here for the first time. [ABSTRACT FROM AUTHOR]

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 127-136-DOI: 10.26355/eurrev_202312_34697 After publication and following some post-publication concerns, the authors have applied the following corrections to the galley proof. -       The conflict of interest section has been amended as follows: J. Kaftalli and G. Marceddu are employees at MAGI EUREGIO. K. Donato is employee at MAGI EUREGIO and MAGISNAT. M. Bertelli is president of MAGI EUREGIO, MAGISNAT, and MAGI's LAB. G. Bonetti, K. Dhuli, A. Macchia, and P.E. Maltese are employees at MAGI's LAB. M. Bertelli, P.E. Maltese, K. Louise Herbst, Sa. Michelini, Se. Michelini, and P. Chiurazzi are patent inventors (US20220362260A1). M. Bertelli, P.E. Maltese, G. Marceddu are patent inventors (US20230173003A1). M. Bertelli, K. Dhuli and P.E. Maltese are patent inventors (WO2022079498A1). M. Bertelli, P.E. Maltese, Sa. Michelini, Se. Michelini, P. Chiurazzi, K. Louise Herbst, J. Kaftalli, K. Donato, and A. Bernini are patent applicants (Application Number 18/516,241). M. Bertelli, K. Donato, P. Chiurazzi, G. Marceddu, K. Dhuli, G. Bonetti and J. Kaftalli are patent applicants (Application Number: 18/466.879). M. Bertelli, G. Bonetti, G. Marceddu, K. Donato, K. Dhuli, J. Kaftalli, Sa. Michelini, and K. Louise Herbst are patent applicants (Application Number 63/495,155). The remaining authors have no conflict of interest to disclose. -       Figure 5 has been modified as follows to better distinguish outliers: -       The legend of Figure 5 has to be modified as follows: Relative expression of AKR1C1 and AKR1C3 in different groups (CTR = non affected controls, L = lipedema patients without overexpression of AKR1C2, L-over = Lipedema patients with overexpression of AKR1C2), showing that lipedema patients expressed AKR1C1 and AKR1C3 levels similar to the control group. Outliers are reported as black triangles. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34697.

Objective: Coronavirus disease 2019 is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. Right now, an increasing number of patients with Post-COVID Syndrome show, without clear evidence of organ dysfunction, a plethora of severe symptoms, such as fatigue, pain, shortness of breath, cognitive impairment, and sleep disturbance. It has already been demonstrated that SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. Several studies have recently documented the presence of autoantibodies in the sera of post-COVID patients, but until now, it is unclear whether the persistence of symptoms could be directly correlated with the presence of autoantibodies., Patients and Methods: In this study, serum autoantibodies (AAbs) levels against four G protein-coupled receptors in 78 patients with post-COVID syndrome have been analyzed. The AAbs investigated are clustered in two groups: adrenergic receptors (α1 and β2) and muscarinic acetylcholine receptors (M3 and M4)., Results: At least one or more AAbs were detected in 60.3% (47/78) of patients diagnosed with post-COVID syndrome, whereas 37.2% (29/78) of patients were positive for all receptors investigated. Interestingly, a strong correlation has been found between AAbs and pain intensity feeling by the patients measured by Visual Analogic Scale. A significant association was also obtained with insomnia and AABS-positive patients., Conclusions: The identification of AAbs and their correlation with pathological symptoms seriousness underly the possible role of AAbs as future therapeutic targets.

Objective: The highly transmissible severe acute respiratory syndrome-Coronavirus-2 was responsible for the 2020 COVID-19 pandemic. COVID-19 mostly affects the respiratory system; however, this infection also affects several other organs. In addition, the sequelae of this disease affect patients for several months after recovery, resulting in long-COVID syndrome., Patients and Methods: In order to characterize the differences between healthy control individuals and long-COVID patients, proteomic profiling of the serum of both groups was performed by mass spectrometry. The obtained data were analyzed with multivariate and univariate statistical analyses., Results: Initially, performing a partial latent square discriminant analysis (PLS-DA) made it possible to identify thirty-three proteins of interest, which were then subjected to a receiver operating characteristic (ROC) analysis. Four proteins were identified as potential stand-alone biomarkers: Sirtuin 1, Natriuretic Peptide B, Hemopexin, and Arachidonate 5-Lipoxygenase. Moreover, a multivariate ROC analysis identified a panel of biomarkers composed of Natriuretic Peptide B, Anterior Gradient 2 Protein, Adiponectin, Endothelin Converting Enzyme 1, Interferon Induced Transmembrane Protein 1, Mannose Binding Lectin 2, Prostaglandin-Endoperoxide Synthase 2, Pirin, Prostaglandin Reductase 1 and Cystatin C., Conclusions: The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Nevertheless, these data should be validated in a larger cohort.

Objective: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported., Patients and Methods: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera., Results: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409)., Conclusions: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Objective: Long-COVID is a clinical syndrome characterized by the presence of symptoms related to SARS-CoV-2 infection that persist for at least four weeks after recovery from COVID-19. Genetics have been proposed to play an important role in long-COVID syndrome onset. This study aimed to identify genetic pathogenetic and likely pathogenetic causative variants of Mendelian genetic diseases in patients with Long-COVID syndrome. Additionally, we aimed to establish an association between these genetic variants and the clinical symptoms manifested during long-COVID syndrome., Patients and Methods: 95 patients affected by long-COVID syndrome were analyzed with a Next-Generation Sequencing (NGS) panel comprising 494 genes. The analyzed genes and the symptoms of the patients collected with an ad-hoc questionnaire were divided into four groups (cardiological, respiratory, immunological, and neurological). Finally, a statistical analysis comprising descriptive statistics, classification based on reported symptoms, and comparative analysis against a control group of healthy individuals was conducted., Results: 12 patients resulted positive for genetic testing with an autosomal dominance (8) or autosomal recessive (4) inheritance, showing a higher prevalence of cardiovascular genetic diseases (9) in the analyzed cohort compared to the normal population. Moreover, the onset of the long-COVID syndrome and its cardiovascular manifestations was compliant with the onset reported in the literature for the identified genetic diseases, suggesting that COVID-19 could manifest late-onset genetic diseases associated with their appearance. Apart from the 12 positive patients, 57 were healthy carriers of genetic diseases. Analyzing the whole cohort, a statistical correlation between prevalent symptomatology and the gene class was established, suggesting an association between the genetic susceptibility of an individual and the possibility of developing specific long-COVID syndrome symptoms, especially cardiovascular symptoms. Furthermore, 17 genetic variants were identified in CFTR. Finally, we identified genetic variants in IFNAR2 and POLG, supporting their respective involvement in inflammation and mitochondria mechanisms, correlated with long-COVID syndrome according to literature data., Conclusions: This study proposed COVID-19 to act as a manifest of underlying late-onset genetic diseases Mendelian associated with carrier status. Moreover, according to our results, mutations in cardiological genes are more present in patients who show cardiological symptoms during the syndrome. This underscores the necessity for cardiological investigation and genetic screening in long-COVID patients to address existing or potential clinical implications.

Objective: Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances., Patients and Methods: Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature., Results: Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role., Conclusions: This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.

Objective: Lipedema is an autosomal dominant genetic disease that mainly affects women. It is characterized by excess deposition of subcutaneous adipose tissue, pain, and anxiety. The genetic and environmental etiology of lipedema is still largely unknown. Although considered a rare disease, this pathology has been suggested to be underdiagnosed or misdiagnosed as obesity or lymphedema. Steroid hormones seem to be involved in the pathogenesis of lipedema. Indeed, aldo-keto reductase family 1 member C1 (AKR1C1), a gene coding for a protein involved in steroid hormones metabolism, was the first proposed to be correlated with lipedema., Patients and Methods: In this study, we employed a molecular dynamics approach to assess the pathogenicity of AKR1C1 genetic variants found in patients with lipedema. Moreover, we combined information theory and structural bioinformatics to identify AKR1C1 polymorphisms from the gnomAD database that could predispose to the development of lipedema., Results: Three genetic variants in AKR1C1 found in patients with lipedema were disruptive to the protein's function. Furthermore, eight AKR1C1  variants found in the general population could predispose to the development of lipedema., Conclusions: The results of this study provide evidence that AKR1C1 may be a key gene in lipedema pathogenesis, and that common polymorphisms could predispose to lipedema development.

Background: This article provides an overview of the application of omics sciences in melanoma research. The name omics sciences refers to the large-scale analysis of biological molecules like DNA, RNA, proteins, and metabolites., Methods: In the course of this review, we have adopted a focu-sed research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources., Results: With the advent of high-throughput technologies, omics have become an essential tool for understanding the complexity of melanoma. In this article, we discuss the different omics approaches used in melanoma research, including genomics, transcriptomics, proteomics, and metabolomics. We also highlight the major findings and insights gained from these studies, including the identification of new therapeutic targets and the development of biomarkers for diagnosis and prognosis. Finally, we discuss the challenges and future directions in omics-based melanoma research, including the integration of multiple omics data and the development of personalized medicine approaches., Conclusions: Overall, this article emphasizes the importance of omics science in advancing our understanding of melanoma and its potential for improving patient outcomes.

Background: Thyroid cancer, a heterogeneous disease originating from the thyroid gland, stands as the predominant endocrine malignan-cy worldwide. Despite advances in diagnosis and treatment, some patients still experience recurrence and mortality, which highlights the need for more personalized approaches to treatment. Omics sciences, encompassing genomics, transcriptomics, proteomics, and metabolomics, offer a high-throughput and impartial methodology for investigating the molecular signatures of thyroid cancer., Methods: In the course of this review, we have adopted a focu-sed research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources., Results: These techniques enable the identification of molecular markers that can aid in diagnosis, prognosis, and treatment selection. As an illustration, through genomics studies, numerous genetic alterations commonly discovered in thyroid cancer have been identified, such as mutations in the BRAF and RAS genes. Through transcriptomics studies, distinctively expressed genes in thyroid cancer have been uncovered, playing roles in diverse biological processes, including cell proliferation, invasion, and metastasis. These genes can serve as potential targets for novel therapies. Proteomics studies have unveiled differentially expressed proteins intricately involved in thyroid cancer pathogenesis, presenting promising biomarkers for early detection and disease progression monitoring. Metabolomics studies have identified alterations in metabolic pathways linked to thyroid cancer, offering promising avenues for potential therapeutic targets., Conclusions: Precision medicine in thyroid cancer involves the integration of omics sciences with clinical data to develop personalized treatment plans for patients. Employing targeted therapies guided by molecular markers has exhibited promising outcomes in enhancing the prognosis of thyroid cancer patients. Notably, those with advanced hyroid cancer carrying BRAF mutations have displayed substantial responses to specific targeted therapies, such as vemurafenib and dabrafenib.

Abstract: This comprehensive review explores the potential of omics sciences - such as genomics, transcriptomics, proteomics, and metabolomics - in advancing the diagnosis and therapy of urothelial carcinoma (UC), a prevalent and heterogeneous cancer affecting the urinary tract. The article emphasizes the significant advancements in understanding the molecular mechanisms underlying UC development and progression, obtained through the application of omics approa-ches. Genomic studies have identified recurrent genetic alterations in UC, while transcriptomic analyses have revealed distinct gene expression profiles associated with different UC subtypes. Proteomic investigations have recognized protein biomarkers with diagnostic and prognostic potential, and metabolomic profiling has found metabolic alterations that are specific to UC. The integration of multi-omics data holds promises in refining UC subtyping, identifying therapeutic targets, and predicting treatment response. However, challenges like the standardization of omics technologies, validation of biomarkers, and ethical considerations need to be addressed to successfully translate these findings into clinical practice. Omics sciences offer tremendous potential in revolutionizing the diagnosis and therapy of UC, enabling more precise diagnostic methods, prognostic evaluations, and personalized treatment selection for UC patients. Future research efforts should focus on overcoming these challenges and translating omics discoveries into meaningful clinical applications to improve outcomes for UC patients.

Background: Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is testicular cancer, accounting for 1% to 2% of all cancers in men., Methods: Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources., Results: The onset and spread of testicular cancer are significantly influenced by genetic changes, including mutations in oncogenes, tu-mor suppressor genes, and DNA repair genes. As a result of identifying these specific genetic mutations in cancers, targeted medications have been developed to disrupt the signaling pathways affected by these genetic changes. To improve the diagnosis and treatment of this disease, it is crucial to understand its natural and clinical histories., Conclusions: In order to comprehend cancer better and to discover new biomarkers and therapeutic targets, oncologists are increasingly employing omics methods, such as genomics, transcriptomics, proteomics, and metabolomics. Targeted medications that focus on specific genetic pathways and mutations hold promise for advancing the diagnosis and management of this disease.

Abstract: In the last decade, renal carcinoma has become more prevalent in European and North American regions. Kidney tumors are usually categorized based on histological features, with renal cell carcinoma being the most common subtype in adults. Despite conventional diagnostic and therapeutic strategies, a rise in cancer incidence and recurrence necessitates a fresh approach to diagnosing and treating kidney cancer. This review focuses on novel multi-omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, and microbiomics, to better understand the molecular and clinical features of renal cell carcinoma. Studies integrating omics sciences have shown early promise in enhancing prognostic and therapeutic outcomes for various kidney cancer subtypes and providing insight into fundamental pathophysiological mechanisms occurring at different molecular levels. This review highlights the importance of utilizing omics sciences as a revolutionary concept in diagnostics and therapeutics and the clinical implications of renal cell carcinoma. Finally, the review presents the most recent findings from large-scale multi-omics studies on renal cell carcinoma and its associations with patient subtyping and drug development.

Abstract: Pancreatic cancer is a leading cause of death worldwide, associated with poor prognosis outcomes and late treatment interventions. The pathological nature and extreme tissue heterogeneity of this disease has hampered all efforts to correctly diagnose and treat it. Omics sciences and precision medicine have revolutionized our understanding of pan-creatic cancer, providing a new hope for patients suffering from this devastating disease. By analyzing large-scale biological data sets and developing personalized treatment strategies, researchers and clinicians are working together to improve patient outcomes and ultimately find a cure for pancreatic cancer.

Abstract: The recent COVID-19 pandemic caused by SARS-CoV-2 affected hundreds of millions of people and caused millions of deaths. There are few effective medications against SARS-CoV-2, and several studies attempted to make drugs based on natural components, such as olive leaves. Olive leaves are rich in polyphenolic compounds, which were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. Polyphenols have renown anti-inflammatory and multitarget antiviral effects on several virus families, which could be among the reasons of the beneficial effects of the Mediterranean diet against COVID-19. This scoping review is focused on the effect of olive tree polyphenols as a natural remedy to inhibit SARS-CoV-2, mainly discussing their influence on the process of viral entry into host cells by endocytosis.

The aim of this study was to assess the association between the TNFR1 rs2234649 polymorphism and ankylosing spondylitis susceptibility in a Russian Caucasian population. A total of 41 ankylosing spondylitis patients and 43 healthy controls, matched according to age and sex, were enrolled, and polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the rs2234649 variant. We evaluated genotype distributions in the patient and control groups with the chi-square test, and assessed the relationship between genotypes and ankylosing spondylitis using the odds ratio. Our analysis showed that the rs2234649 polymorphism does not increase ankylosing spondylitis risk. In conclusion, the TNFR1 gene polymorphism tested does not appear to be useful for assessing predisposition to this disease or for its diagnosis or prognosis.

The aim of this review is to describe a series of ten genetic diseases with Mendelian inheritance pattern in people of low- or middle-income countries, which can be easily identified with simple and affordable methods. Recent information shows that although genetic diseases account for more than 10% of infant mortality in such countries, testing, counseling, and treatment of genetic diseases is not a priority. The selection criteria for the genetic tests that are discussed in this review are: i) the frequency of the genetic disease in the general population, ii) the cost and ease of execution, and iii) the report of validated methods in the literature for the diagnosis of these diseases. The goal is to promote diagnosis of genetic diseases at low-cost and with relative ease, thereby enabling appropriate treatments, reducing mortality, and preventing genetic diseases in high-risk families.

Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m 2 , early onset and a family history of being overweight. Candidate genes were screened by direct sequence analysis to search for rare genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for its influence on the BMI (in obesity patients) and for obesity risk, using a case-control study involving 117 healthy individuals. Two different non-synonymous alterations in MC4R were found in two patients: the p.(Thr112Met), previously described in the literature as a probable gene involved in the obesity phenotype, and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico evaluations and family segregation studies. The LEP -2548 G/A polymorphism was not associated with the BMI or obesity risk. In conclusion, we have reported a novel mutation in MC4R in a family of Italian patients with severe obesity. Screening for MC4R could be important for directing the carriers of mutations towards therapy including partial agonists of the MC4R that could normalize their appetite and inhibit compulsive eating. Next-generation sequencing could be used to clarify the genetic basis of obesity in the future.

Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion. This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance. Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work. The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue. Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores. No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS. In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS., Competing Interests: The authors declare no conflict of interest.

In this study, we assessed the prevalence of polymorphisms in genes involved in hyperhomocysteinemia or hemostasis to shed light on their role, if any, in retinal vein occlusion (RVO). We recruited 37 Italian patients (17 men and 20 women) with a diagnosis of central or branch RVO based on fundus examination and retinal fluorescein angiography, as well as 45 healthy controls. Risk factors and family history of RVO of all subjects were recorded. The distributions of polymorphisms in patients and controls were evaluated using the χ(2) test and OR. We confirmed an increased risk in subjects with dyslipidemia (high density lipoprotein <59 mg/dL: 17.8% of controls, 43.2% of patients, P = 0.0002; low density lipoprotein >130 mg/dL: 26.7% controls, 54.1% patients, P = 0.0002), arterial hypertension (60% controls, 75.7% patients, P = 0.023), and high body mass index (28.9% controls, 70.3% patients, P < 0.0001, and excluded involvement of the selected polymorphisms in RVO. Overall, the tested polymorphisms did not appear to be useful for assessing predisposition or for the diagnosis and prognosis of RVO.