Research

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16 pages, 2193 KiB

Open AccessArticle

Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line

by Ayse Banu Demir, Domenico Benvenuto, Bilge Karacicek, Yasemin Erac, Silvia Spoto, Silvia Angeletti, Massimo Ciccozzi and Metiner Tosun

J. Pers. Med. 2022, 12(12), 2065; https://doi.org/10.3390/jpm12122065 - 14 Dec 2022

Cited by 1 | Viewed by 1756

Abstract

Elevated levels of STIM1, an endoplasmic reticulum Ca²⁺ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs [...] Read more.

Elevated levels of STIM1, an endoplasmic reticulum Ca²⁺ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca²⁺ homeostasis-associated genes in STIM1- or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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10 pages, 827 KiB

Open AccessFeature PaperArticle

SARS-CoV-2 Variants in COVID-19 Disease: A Focus on Disease Severity and Vaccine Immunity in Patients Admitted to the Emergency Department

by Marta Fogolari, Maria Francesconi, Lucia De Florio, Marta Giovanetti, Roberta Veralli, Cecilia De Flora, Antonello Maruotti, Fabio Scarpa, Silvia Spoto, Federica Sambuco, Elisabetta Riva, Massimo Ciccozzi and Silvia Angeletti

J. Pers. Med. 2022, 12(12), 2001; https://doi.org/10.3390/jpm12122001 - 02 Dec 2022

Viewed by 1502

Abstract

Tracking SARS-CoV-2 variants along with vaccinations are fundamental for severe COVID-19 disease prevention. A study was performed that focused on 43 patients with the SARS-CoV-2 infection who were admitted to the Emergency Department. RT-PCR–positive nasopharyngeal samples were sequenced using the MiSeq II system [...] Read more.

Tracking SARS-CoV-2 variants along with vaccinations are fundamental for severe COVID-19 disease prevention. A study was performed that focused on 43 patients with the SARS-CoV-2 infection who were admitted to the Emergency Department. RT-PCR–positive nasopharyngeal samples were sequenced using the MiSeq II system for variant detection. The main reason for Emergency Department admission was COVID-19 (67%), followed by other causes (33%); 51% patients were unvaccinated or vaccinated with a single dose and 49% had completed the vaccination course with two or three doses. Among the vaccinated group, 38% were admitted for COVID-19, versus 94.5% of the unvaccinated group. After admission, 50% of the vaccinated group and 36% of the unvaccinated group were discharged and allowed to go home, and 80% of the unvaccinated had no major comorbidities; 63% needed hospital admission and 5% required a stay in the Intensive Care Unit. Of these, 37% were vaccinated with 3 doses, 11% with two doses, 4% with a single dose, and 48% were unvaccinated. The 70% of the vaccinated patients who were admitted to hospital presented major comorbidities versus 38% of the unvaccinated group. Two unvaccinated patients that needed intensive care had relevant comorbidities and died. Genome sequencing showed the circulation of three omicron and two pure sub-lineages of omicron, including 22 BA.1, 12 BA.1.1, and 7 BA.2. Data showed the SARS-CoV-2 national and international migration patterns and how vaccination was useful for severe COVID-19 disease prevention. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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10 pages, 1655 KiB

Open AccessFeature PaperArticle

Speckle Contrast as Retinal Tissue Integrity Biomarker in Patients with Type 1 Diabetes Mellitus with No Retinopathy

by Elvira Orduna-Hospital, Maria Arcas-Carbonell, Ana Sanchez-Cano, Isabel Pinilla and Alejandra Consejo

J. Pers. Med. 2022, 12(11), 1807; https://doi.org/10.3390/jpm12111807 - 01 Nov 2022

Viewed by 1195

Abstract

Purpose: To study the retinal and choroidal layers in type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR), using speckle contrast of optical coherence tomography (OCT) images as a tissue biomarker in comparison with healthy subjects. Methods: OCT Spectralis images of 148 eyes, [...] Read more.

Purpose: To study the retinal and choroidal layers in type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR), using speckle contrast of optical coherence tomography (OCT) images as a tissue biomarker in comparison with healthy subjects. Methods: OCT Spectralis images of 148 eyes, 84 from DM1 patients without DR signs, and 64 belonging to the control group, were collected. The speckle contrast and thickness of the inner retinal layer (IRL), the outer retinal layer (ORL), and the choroidal layer in the nasal parafoveal area (N3), were prospectively analyzed. Results: A statistically significant difference (p = 0.001) in the IRL thickness between groups was observed, being thicker in the DM1 group. There were no differences in the ORL and choroidal thicknesses between groups. A statistically significant difference (p = 0.02) in the IRL speckle contrast was obtained, being lower in the DM1 group. The maximum speckle contrast was reached in the ORL for both groups, although in the DM1 group, it occurs closer to the choroid, at 64 ± 8 μm (p = 0.008). Conclusions: Statistically significant differences were found in speckle contrast and thickness between the control and the DM1 group, suggesting an IRL alteration of DM1 patients, supporting the retinal neurodegeneration before DR signs are observed. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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12 pages, 486 KiB

Open AccessArticle

Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis

by Dmitry S. Mikhaylenko, Ekaterina B. Kuznetsova, Viktoria V. Musatova, Irina V. Bure, Tatiana A. Deryagina, Ekaterina A. Alekseeva, Vadim V. Tarasov, Andrey A. Zamyatnin, Jr. and Marina V. Nemtsova

J. Pers. Med. 2022, 12(4), 641; https://doi.org/10.3390/jpm12040641 - 15 Apr 2022

Cited by 3 | Viewed by 1944

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from [...] Read more.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of IL6, IL6R, TNFRSF1A, CTLA4, IL10, IL23R, and PADI4; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes (IL1B, IL17A, PADI4, DHODH, GLCCI1, IL23R, and TNFAIP3), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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15 pages, 1707 KiB

Open AccessFeature PaperArticle

ILB^® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

by Giacomo Lazzarino, Renata Mangione, Antonio Belli, Valentina Di Pietro, Zsuzsanna Nagy, Nicholas M. Barnes, Lars Bruce, Bernardo M. Ropero, Lennart I. Persson, Benedetta Manca, Miriam Wissam Saab, Angela M. Amorini, Barbara Tavazzi, Giuseppe Lazzarino and Ann Logan

J. Pers. Med. 2021, 11(8), 794; https://doi.org/10.3390/jpm11080794 - 14 Aug 2021

Cited by 6 | Viewed by 5452

Abstract

Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in [...] Read more.

Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB^®. A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients’ clinical conditions, indicating a response to ILB^® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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Review

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15 pages, 1963 KiB

Open AccessReview

Cytokines and Hepatocellular Carcinoma: Biomarkers of a Deadly Embrace

by Krizia Pocino, Annunziata Stefanile, Valerio Basile, Cecilia Napodano, Francesca D’Ambrosio, Riccardo Di Santo, Cinzia Anna Maria Callà, Francesca Gulli, Raffaele Saporito, Gabriele Ciasca, Francesco Equitani, Umberto Basile and Mariapaola Marino

J. Pers. Med. 2023, 13(1), 5; https://doi.org/10.3390/jpm13010005 - 20 Dec 2022

Cited by 6 | Viewed by 1984

Abstract

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the [...] Read more.

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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18 pages, 1119 KiB

Open AccessFeature PaperReview

Biomarkers Predictive of Metabolic Syndrome and Cardiovascular Disease in Childhood Cancer Survivors

by Alberto Romano, Ester Del Vescovo, Serena Rivetti, Silvia Triarico, Giorgio Attinà, Stefano Mastrangelo, Palma Maurizi and Antonio Ruggiero

J. Pers. Med. 2022, 12(6), 880; https://doi.org/10.3390/jpm12060880 - 27 May 2022

Cited by 8 | Viewed by 2512

Abstract

The improvement in childhood cancer treatments resulted in a marked improvement in the survival of pediatric cancer patients. However, as survival increased, it was also possible to observe the long-term side effects of cancer therapies. Among these, metabolic syndrome is one of the [...] Read more.

The improvement in childhood cancer treatments resulted in a marked improvement in the survival of pediatric cancer patients. However, as survival increased, it was also possible to observe the long-term side effects of cancer therapies. Among these, metabolic syndrome is one of the most frequent long-term side effects, and causes high mortality and morbidity. Consequently, it is necessary to identify strategies that allow for early diagnosis. In this review, the pathogenetic mechanisms of metabolic syndrome and the potential new biomarkers that can facilitate its diagnosis in survivors of pediatric tumors are analyzed. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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12 pages, 277 KiB

Open AccessReview

How Genetics Can Improve Clinical Practice in Chronic Kidney Disease: From Bench to Bedside

by Doloretta Piras, Nicola Lepori, Gianfranca Cabiddu and Antonello Pani

J. Pers. Med. 2022, 12(2), 193; https://doi.org/10.3390/jpm12020193 - 31 Jan 2022

Cited by 1 | Viewed by 2258

Abstract

Chronic kidney disease (CKD) is considered a major global health problem with high socio-economic costs: the risk of CKD in individuals with an affected first degree relative has been found to be three times higher than in the general population. Genetic factors are [...] Read more.

Chronic kidney disease (CKD) is considered a major global health problem with high socio-economic costs: the risk of CKD in individuals with an affected first degree relative has been found to be three times higher than in the general population. Genetic factors are known to be involved in CKD pathogenesis, both due to the possible presence of monogenic pathologies as causes of CKD, and to the role of numerous gene variants in determining susceptibility to the development of CKD. The genetic study of CKD patients can represent a useful tool in the hands of the clinician; not only in the diagnostic and prognostic field, but potentially also in guiding therapeutic choices and in designing clinical trials. In this review we discuss the various aspects of the role of genetic analysis on clinical management of patients with CKD with a focus on clinical applications. Several topics are discussed in an effort to provide useful information for daily clinical practice: definition of susceptibility to the development of CKD, identification of unrecognized monogenic diseases, reclassification of the etiological diagnosis, role of pharmacogenetics. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

14 pages, 1591 KiB

Open AccessReview

Molecular and Genetic Immune Biomarkers of Primary and Immune-Therapy Induced Hypophysitis: From Laboratories to the Clinical Practice

by Sabrina Chiloiro, Filippo Russo, Tommaso Tartaglione and Ettore Domenico Capoluongo

J. Pers. Med. 2021, 11(10), 1026; https://doi.org/10.3390/jpm11101026 - 15 Oct 2021

Cited by 7 | Viewed by 2034

Abstract

Hypophysitis is a rare and potentially life-threatening disease, characterized by an elevated risk of complications, such as the occurrence of acute central hypoadrenalism, persistent hypopituitarism, or the extension of the inflammatory process to the neighboring neurological structures. In recent years, a large number [...] Read more.

Hypophysitis is a rare and potentially life-threatening disease, characterized by an elevated risk of complications, such as the occurrence of acute central hypoadrenalism, persistent hypopituitarism, or the extension of the inflammatory process to the neighboring neurological structures. In recent years, a large number of cases has been described. The diagnosis of hypophysitis is complex because it is based on clinical and radiological criteria. Due to this, the integration of molecular and genetic biomarkers can help physicians in the diagnosis of hypophysitis and play a role in predicting disease outcome. In this paper, we review current knowledge about molecular and genetic biomarkers of hypophysitis with the aim of suggesting a possible integration of these biomarkers in clinical practice. Full article

(This article belongs to the Special Issue Novel Biomarkers in Translational Medicine of Chronic and Autoimmune Diseases)

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