Biomedicines

13 pages, 7545 KiB

Open AccessReview

Strain Echocardiography in Acute COVID-19 and Post-COVID Syndrome: More than Just a Snapshot

by Johannes Kersten, Jana Schellenberg, Achim Jerg, Johannes Kirsten, Hasema Persch, Yuefei Liu and Jürgen M. Steinacker

Biomedicines 2023, 11(4), 1236; https://doi.org/10.3390/biomedicines11041236 - 21 Apr 2023

Cited by 2 | Viewed by 3155

Abstract

Speckle-tracking echocardiography (STE) has become an established, widely available diagnostic method in the past few years, making its value clear in cases of COVID-19 and the further course of the disease, including post-COVID syndrome. Since the beginning of the pandemic, many studies have [...] Read more.

Speckle-tracking echocardiography (STE) has become an established, widely available diagnostic method in the past few years, making its value clear in cases of COVID-19 and the further course of the disease, including post-COVID syndrome. Since the beginning of the pandemic, many studies have been published on the use of STE in this condition, enabling, on the one hand, a better understanding of myocardial involvement in COVID-19 and, on the other, a better identification of risk to patients, although some questions remain unanswered in regard to specific pathomechanisms, especially in post-COVID patients. This review takes a closer look at current findings and potential future developments by summarising the extant data on the use of STE, with a focus on left and right ventricular longitudinal strain. Full article

(This article belongs to the Special Issue Emerging Trends in COVID-19 and Heart Failure)

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18 pages, 5742 KiB

Open AccessArticle

High Fidelity Pressure Wires Provide Accurate Validation of Non-Invasive Central Blood Pressure and Pulse Wave Velocity Measurements

by Alessandro Scalia, Chadi Ghafari, Wivine Navarre, Philippe Delmotte, Rob Phillips and Stéphane Carlier

Biomedicines 2023, 11(4), 1235; https://doi.org/10.3390/biomedicines11041235 - 21 Apr 2023

Viewed by 1931

Abstract

Central blood pressure (cBP) is known to be a better predictor of the damage caused by hypertension in comparison with peripheral blood pressure. During cardiac catheterization, we measured cBP in the ascending aorta with a fluid-filled guiding catheter (FF) in 75 patients and [...] Read more.

Central blood pressure (cBP) is known to be a better predictor of the damage caused by hypertension in comparison with peripheral blood pressure. During cardiac catheterization, we measured cBP in the ascending aorta with a fluid-filled guiding catheter (FF) in 75 patients and with a high-fidelity micromanometer tipped wire (FFR) in 20 patients. The wire was withdrawn into the brachial artery and aorto-brachial pulse wave velocity (abPWV) was calculated from the length of the pullback and the time delay between the ascending aorta and the brachial artery pulse waves by gating to the R-wave of the ECG for both measurements. In 23 patients, a cuff was inflated around the calf and an aorta-tibial pulse wave velocity (atPWV) was calculated from the distance between the cuff around the leg and the axillary notch and the time delay between the ascending aorta and the tibial pulse waves. Brachial BP was measured non-invasively and cBP was estimated using a new suprasystolic oscillometric technology. The mean differences between invasively measured cBP by FFR and non-invasive estimation were −0.4 ± 5.7 mmHg and by FF 5.4 ± 9.4 mmHg in 52 patients. Diastolic and mean cBP were both overestimated by oscillometry, with mean differences of −8.9 ± 5.5 mmHg and −6.4 ± 5.1 mmHg compared with the FFR and −10.6 ± 6.3 mmHg and −5.9 ± 6.2 mmHg with the FF. Non-invasive systolic cBP compared accurately with the high-fidelity FFR measurements, demonstrating a low bias (≤5 mmHg) and high precision (SD ≤ 8 mmHg). These criteria were not met when using the FF measurements. Invasively derived average Ao-brachial abPWV was 7.0 ± 1.4 m/s and that of Ao-tibial atPWV was 9.1 ± 1.8 m/s. Non-invasively estimated PWV based on the reflected wave transit time did not correlate with abPWV or with atPWV. In conclusion, we demonstrate the advantages of a novel method of validation for non-invasive cBP monitoring devices using acknowledged gold standard FFR wire transducers and the possibility to easily measure PWV during coronary angiography with the impact of cardiovascular risk factors. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases (CVD))

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29 pages, 4247 KiB

Open AccessReview

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses

by Sofia Carvalho, Juliana Inês Santos, Luciana Moreira, Mariana Gonçalves, Hugo David, Liliana Matos, Marisa Encarnação, Sandra Alves and Maria Francisca Coutinho

Biomedicines 2023, 11(4), 1234; https://doi.org/10.3390/biomedicines11041234 - 21 Apr 2023

Cited by 2 | Viewed by 3124

Abstract

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological [...] Read more.

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Lysosomal Storage Diseases: From Pathogenesis to Therapeutic Strategies 2.0)

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18 pages, 11213 KiB

Open AccessArticle

The Enhanced Expression of ZWILCH Predicts Poor Survival of Adrenocortical Carcinoma Patients

by Małgorzata Blatkiewicz, Kacper Kamiński, Marta Szyszka, Zaid Al-Shakarchi, Anna Olechnowicz, Ewelina Stelcer, Hanna Komarowska, Marianna Tyczewska, Anna Klimont, Marek Karczewski, Tomasz Wierzbicki, Joanna Mikołajczyk-Stecyna, Marek Ruchała, Ludwik K. Malendowicz and Marcin Ruciński

Biomedicines 2023, 11(4), 1233; https://doi.org/10.3390/biomedicines11041233 - 21 Apr 2023

Cited by 4 | Viewed by 2392

Abstract

Zwilch kinetochore protein (ZWILCH) plays a key role in proper cell proliferation. The upregulation of the ZWILCH gene was observed in many types of cancers, but the association of ZWILCH with adrenocortical carcinoma (ACC) was not investigated so far. The main aim of [...] Read more.

Zwilch kinetochore protein (ZWILCH) plays a key role in proper cell proliferation. The upregulation of the ZWILCH gene was observed in many types of cancers, but the association of ZWILCH with adrenocortical carcinoma (ACC) was not investigated so far. The main aim of the presented study was to verify if the enhanced level of the ZWILCH gene can be used as a diagnostic marker for ACC development and progression, as well as a predictor of survival time for ACC patients. The performed analyses included investigation of the ZWILCH expression profile in tumors with publicly available TCGA (The Cancer Genome Atlas) datasets and transcriptomic data from the Gene Expression Omnibus (GEO) database, as well as, in human biological samples of normal adrenal, adrenocortical carcinoma and in commercially available tissue microarrays. The findings demonstrate statistically significant higher ZWILCH gene expression in ACC tissue in comparison with normal adrenal glands. Furthermore, there is a strong correlation between ZWILCH upregulation and tumor mitotic rate and the probability of patient survival. The enhanced ZWILCH level is also connected with the activation of genes involved in cell proliferation and the inhibition of genes related to the immune system. This work contributes to a better understanding of the role of ZWILCH as an ACC biomarker and diagnostic tool. Full article

(This article belongs to the Special Issue Pathogenesis and Treatment of Adrenal Tumors 2.0)

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19 pages, 7549 KiB

Open AccessArticle

Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma

by Yuanqin Zhou, Xianzhu Pan, Yakun Liu, Xiaofei Li, Keqiong Lin, Jicheng Zhu, Li Zhan, Chen Kan and Hong Zheng

Biomedicines 2023, 11(4), 1232; https://doi.org/10.3390/biomedicines11041232 - 21 Apr 2023

Cited by 1 | Viewed by 2015

Abstract

Hepatocellular carcinoma (HCC) is an aggressive and challenging disease to treat. Due to the lack of effective early diagnosis and therapy for the illness, it is crucial to identify novel biomarkers that can predict tumor behavior in HCC. In such cases, family with [...] Read more.

Hepatocellular carcinoma (HCC) is an aggressive and challenging disease to treat. Due to the lack of effective early diagnosis and therapy for the illness, it is crucial to identify novel biomarkers that can predict tumor behavior in HCC. In such cases, family with sequence similarity 210 member B (FAM210B) is abundant in various human tissues, but its regulatory mechanisms and role in various tissues remain unclear. In this study, we analyzed the expression pattern of FAM210B in HCC using public gene expression databases and clinical tissue samples. Our results confirmed that FAM210B was dysregulated in both HCC cell lines and HCC paraffin section samples. FAM210B depletion significantly increased the capacity of cells to grow, migrate, and invade in vitro, while overexpression of FAM210B suppressed tumor growth in a xenograft tumor model. Furthermore, we identified FAM210B’s involvement in MAPK signaling and p-AKT signaling pathways, both of which are known oncogenic signaling pathways. In summary, our study provides a rational basis for the further investigation of FAM210B as a valuable biological marker for diagnosing and predicting the prognosis of HCC patients. Full article

(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of Liver Disease)

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30 pages, 3332 KiB

Open AccessReview

Bioengineered Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles as an Improved Drug Delivery System: Methods and Applications

by Cristiana Ulpiano, Cláudia L. da Silva and Gabriel A. Monteiro

Biomedicines 2023, 11(4), 1231; https://doi.org/10.3390/biomedicines11041231 - 21 Apr 2023

Cited by 4 | Viewed by 3359

Abstract

Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell–cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their [...] Read more.

Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell–cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their high modification flexibility, make them promising drug delivery vehicles for cell-free therapies. Mesenchymal stromal cells (MSCs) are known for their great paracrine trophic activity, which is largely sustained by the secretion of EVs. MSC-derived EVs (MSC-EVs) retain important features of the parental cells and can be bioengineered to improve their therapeutic payload and target specificity, demonstrating increased therapeutic potential in numerous pre-clinical animal models, including in the treatment of cancer and several degenerative diseases. Here, we review the fundamentals of EV biology and the bioengineering strategies currently available to maximize the therapeutic value of EVs, focusing on their cargo and surface manipulation. Then, a comprehensive overview of the methods and applications of bioengineered MSC-EVs is presented, while discussing the technical hurdles yet to be addressed before their clinical translation as therapeutic agents. Full article

(This article belongs to the Special Issue Mesenchymal Stromal Cells in Human Disease and Therapy)

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15 pages, 2869 KiB

Open AccessArticle

MyBrain-Seq: A Pipeline for MiRNA-Seq Data Analysis in Neuropsychiatric Disorders

by Daniel Pérez-Rodríguez, Roberto Carlos Agís-Balboa and Hugo López-Fernández

Biomedicines 2023, 11(4), 1230; https://doi.org/10.3390/biomedicines11041230 - 21 Apr 2023

Cited by 2 | Viewed by 3969

Abstract

High-throughput sequencing of small RNA molecules such as microRNAs (miRNAs) has become a widely used approach for studying gene expression and regulation. However, analyzing miRNA-Seq data can be challenging because it requires multiple steps, from quality control and preprocessing to differential expression and [...] Read more.

High-throughput sequencing of small RNA molecules such as microRNAs (miRNAs) has become a widely used approach for studying gene expression and regulation. However, analyzing miRNA-Seq data can be challenging because it requires multiple steps, from quality control and preprocessing to differential expression and pathway-enrichment analyses, with many tools and databases available for each step. Furthermore, reproducibility of the analysis pipeline is crucial to ensure that the results are accurate and reliable. Here, we present myBrain-Seq, a comprehensive and reproducible pipeline for analyzing miRNA-Seq data that incorporates miRNA-specific solutions at each step of the analysis. The pipeline was designed to be flexible and user-friendly, allowing researchers with different levels of expertise to perform the analysis in a standardized and reproducible manner, using the most common and widely used tools for each step. In this work, we describe the implementation of myBrain-Seq and demonstrate its capacity to consistently and reproducibly identify differentially expressed miRNAs and enriched pathways by applying it to a real case study in which we compared schizophrenia patients who responded to medication with treatment-resistant schizophrenia patients to obtain a 16-miRNA treatment-resistant schizophrenia profile. Full article

(This article belongs to the Special Issue Genome-Environment Interactions in Psychiatric Disorders and Neurodegenerative Diseases)

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14 pages, 2240 KiB

Open AccessArticle

Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271

by Francesca Beretti, Martina Gatti, Manuela Zavatti, Sara Bassoli, Giovanni Pellacani and Tullia Maraldi

Biomedicines 2023, 11(4), 1229; https://doi.org/10.3390/biomedicines11041229 - 20 Apr 2023

Cited by 5 | Viewed by 2051

Abstract

BRAF mutations are present in 30–50% of cases of cutaneous melanoma, and treatment with selective BRAF and MEK inhibitors has been introduced. However, the development of resistance to these drugs often occurs. Chemo-resistant melanoma cells show increased expression of CD271, a stem cell [...] Read more.

BRAF mutations are present in 30–50% of cases of cutaneous melanoma, and treatment with selective BRAF and MEK inhibitors has been introduced. However, the development of resistance to these drugs often occurs. Chemo-resistant melanoma cells show increased expression of CD271, a stem cell marker that features increased migration. Concordantly, resistance to the selective inhibitor of oncogenic BRAFV600E/K, vemurafenib, is mediated by the increased expression of CD271. It has recently been shown that the BRAF pathway leads to an overexpression of the NADPH oxidase Nox4, which produces reactive oxygen species (ROS). Here, we examined in vitro how Nox-derived ROS in BRAF-mutated melanoma cells regulates their drug sensitivity and metastatic potential. We demonstrated that DPI, a Nox inhibitor, reduced the resistance of a melanoma cell line (SK-MEL-28) and a primary culture derived from a BRAFV600E-mutated biopsy to vemurafenib. DPI treatment affected the expression of CD271 and the ERK and Akt signaling pathways, leading to a drop in epithelial–mesenchymal transition (EMT), which undoubtedly promotes an invasive phenotype in melanoma. More importantly, the scratch test demonstrated the efficacy of the Nox inhibitor (DPI) in blocking migration, supporting its use to counteract drug resistance and thus cell invasion and metastasis in BRAF-mutated melanoma. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cancer Drug Resistance)

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14 pages, 1162 KiB

Open AccessArticle

Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan

by Murad Ali Rahat, Fazal Akbar, Akhtar Rasool, Muhammad Ilyas, Allah Rakha, Sulaiman Shams, Musharraf Jelani, Fehmida Bibi, Bader H. Shirah, Angham Abdulrhman Abdulkareem, Muhammad Imran Naseer and Muhammad Israr

Biomedicines 2023, 11(4), 1228; https://doi.org/10.3390/biomedicines11041228 - 20 Apr 2023

Cited by 2 | Viewed by 3324

Abstract

The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the [...] Read more.

The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division. Methods: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected. Multiplexed SNaPshot single base extension chemistry was used, and the genotypic results were analysed. Snapshot data were used for eye colour prediction through the IrisPlex and FROG-kb tool. Results: The results of the present study found brown eye colour to be the most prevalent eye colour in comparison to intermediate and blue coloured. Overall, individuals with brown-coloured eyes possess CT (46.84%) and TT (53.16%) genotypes. Blue eye-coloured individuals are solely of the CC genotype, while individuals of intermediate eye colour carry CT (45.15%) and CC (53.85%) genotypes in rs12913832 SNP in the HERC2 gene. It was also revealed that brown-coloured eyes individuals were dominant among all age groups followed by intermediate and blue. Statistical analysis between particular variables and eye colour showed a significant p-value (<0.05) for rs16891982 SNP in SLC45A2 gene, rs12913832 SNP in HERC2 gene, rs1393350 SNP in SLC45A2, districts and gender. The rest of the SNPs were non-significant with eye colour, respectively. The rs12896399 SNP and SNP rs1800407 were found significant with rs16891982 SNP. The result also demonstrated that the study group differs from the world population based on eye colour. The two eye colour prediction results were compared, and it was discovered that IrisPlex and FROG-Kb had similar higher prediction ratios for Brown and Blue eye colour. Conclusions: The results of the current study revealed brown eye colour to be the most prevalent amongst members of the local population of Pakhtoon ethnicity in the Malakand Division of northern Pakistan. A set of contemporary human DNA samples with known phenotypes are used in this research to evaluate the custom panel’s prediction accuracy. With the aid of this forensic test, DNA typing can be supplemented with details about the appearance of the person from whom the sample was taken in cases involving missing persons, ancient human remains, and trace samples. This study may be helpful for future population genetics and forensics studies. Full article

(This article belongs to the Special Issue Genetic Research on Neurodevelopmental Disorders)

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10 pages, 625 KiB

Open AccessReview

Health Disparities in Multiple Sclerosis among Hispanic and Black Populations in the United States

by Michael Z. Moore, Carlos A. Pérez, George J. Hutton, Hemali Patel and Fernando X. Cuascut

Biomedicines 2023, 11(4), 1227; https://doi.org/10.3390/biomedicines11041227 - 20 Apr 2023

Cited by 4 | Viewed by 2332

Abstract

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents [...] Read more.

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will review the current understanding about the patterns of disease presentation, genetic considerations, response to treatment, roles of social determinants of health, and healthcare utilization. In addition, we explore future directions of inquiry as well as practical methods of meeting these challenges. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)

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14 pages, 1064 KiB

Open AccessReview

T2-Low Asthma: A Discussed but Still Orphan Disease

by Francesca Peri, Alessandro Amaddeo, Laura Badina, Massimo Maschio, Egidio Barbi and Sergio Ghirardo

Biomedicines 2023, 11(4), 1226; https://doi.org/10.3390/biomedicines11041226 - 20 Apr 2023

Cited by 8 | Viewed by 2910

Abstract

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas [...] Read more.

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20–30% of all patients with asthma. Neutrophilic asthma’s prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: “neutrophilic asthma”, “non-type 2 asthma” and “paucigranulocytic asthma”. We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease. Full article

(This article belongs to the Special Issue Pathogenesis and Novel Therapeutics in Asthma Volume II)

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9 pages, 514 KiB

Open AccessCase Report

Isolated Progression of Multiple Myeloma into the Extramedullary Plasmacytoma of Dura Mater: A Case Report and Review of the Literature

by Agata Tyczyńska, Mikołaj Turski, Ewa Zarzycka and Jan Maciej Zaucha

Biomedicines 2023, 11(4), 1225; https://doi.org/10.3390/biomedicines11041225 - 20 Apr 2023

Cited by 1 | Viewed by 2237

Abstract

Multiple myeloma (MM) is a disease caused by the uncontrolled proliferation of clonal plasma cells in bone marrow. Extramedullary plasma cell infiltrations may occur at the time of diagnosis but usually arise during systemic disease progression. Central nervous system (CNS) plasmacytomas are extremely [...] Read more.

Multiple myeloma (MM) is a disease caused by the uncontrolled proliferation of clonal plasma cells in bone marrow. Extramedullary plasma cell infiltrations may occur at the time of diagnosis but usually arise during systemic disease progression. Central nervous system (CNS) plasmacytomas are extremely rare (less than 1% of patients with MM) and usually occur as a result of systemic disease progression. The frequency of extramedullary progression to CNS without simultaneous systemic progression is not known. Here, we present a challenging case in which local disease progression to CNS occurred without any signs of systemic progression. The extramedullary plasmacytoma originated from the dura mater of the brain mimicking a brain tumor. We review and discuss further treatment options that are available in such rare clinical scenarios in relation to the treatment already undertaken. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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13 pages, 1728 KiB

Open AccessArticle

Assessment of Selected Immune Parameters in Patients Undergoing Cardiac Surgery with the Use of Cardiopulmonary Bypass: Aspects of Age and Sex—A Pilot Study

by Piotr Sindera, Ewa Kucewicz-Czech and Grażyna Wilczek

Biomedicines 2023, 11(4), 1224; https://doi.org/10.3390/biomedicines11041224 - 20 Apr 2023

Viewed by 1907

Abstract

The present study aimed to assess the changes in the immunological parameters of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The serum or plasma samples of patients were assessed to determine the concentrations of IL-6, one of the major proinflammatory cytokines (seven [...] Read more.

The present study aimed to assess the changes in the immunological parameters of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The serum or plasma samples of patients were assessed to determine the concentrations of IL-6, one of the major proinflammatory cytokines (seven females and six males), and selected classes of immunoglobulins (six females and seven males). The samples for ELISA (enzyme-linked immunosorbent assay) were collected from patients before the use of CPB, at 60 min of the use of CPB, and at 24 h after the surgery. After 24 h of the surgery, IL-6, IgM, and IgG concentrations were higher in the serum of female patients than in the serum of male patients. However, compared to female patients, male patients showed a significant increase in IgG3 concentration after 24 h of the surgery. Regardless of age, the levels of the analyzed classes of immunoglobulins were similar in all patients. Additionally, in both age groups, a significant increase in the serum IL-6 concentration was observed after the first postoperative day, and this increase was more pronounced in patients diagnosed to have postoperative infections. The serum IL-6 concentration can serve as a potential marker of pathogenic infections in patients undergoing cardiac surgery with CPB and is thus useful for the early diagnosis of postoperative infections. Full article

(This article belongs to the Special Issue State-of-the-Art Gene-Target and Cell Therapy in Poland)

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18 pages, 4909 KiB

Open AccessArticle

Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer

by Chrispus M. Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix F. Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu and Jin-Ming Yang

Biomedicines 2023, 11(4), 1223; https://doi.org/10.3390/biomedicines11041223 - 20 Apr 2023

Cited by 5 | Viewed by 3332

Abstract

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such [...] Read more.

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated with the status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Enhanced infiltration of immunosuppressive cells was also positively correlated with the expression of these five genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expression of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment. Full article

(This article belongs to the Special Issue Molecular Research of Triple-Negative Breast Cancer)

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11 pages, 494 KiB

Open AccessArticle

A Pilot Study of Implementing Diabetic Retinopathy Screening in the Oslo Region, Norway: Baseline Results

by Ellen Steffenssen Sauesund, Øystein Kalsnes Jørstad, Cathrine Brunborg, Morten Carstens Moe, Maja Gran Erke, Dag Sigurd Fosmark and Goran Petrovski

Biomedicines 2023, 11(4), 1222; https://doi.org/10.3390/biomedicines11041222 - 19 Apr 2023

Cited by 3 | Viewed by 2059

Abstract

Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 [...] Read more.

Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 years) with type 1 or 2 DM (T1D and T2D). We measured the best-corrected visual acuity (BCVA), blood pressure (BP), heart rate (HR), intraocular pressure (IOP), height and weight. We also collected HbA1c, total serum cholesterol and urine-albumin, -creatinine and -albumin-to-creatinine ratio (ACR), as well as socio-demographic parameters, medications and previous screening history. We obtained color fundus photographs, which were graded by two experienced ophthalmologists according to the International Clinical Disease Severity Scale for DR. Results: The study included 180 eyes of 90 patients: 12 patients (13.3%) had T1D and 78 (86.7%) had T2D. In the T1D group, 5 patients (41.7%) had no DR, and 7 (58.3%) had some degree of DR. In the T2D group, 60 patients (76.9%) had no DR, and 18 (23.1%) had some degree of DR. None of the patients had proliferative DR. Of the 43 patients not newly diagnosed (time of diagnosis > 5 years for T1D and >1 years for T2D), 37.5% of the T1D patients and 5.7% of the T2D patients had previously undergone regular screening. Univariate analyses found for the whole cohort significant associations between DR and age, HbA1c, urine albumin-to-creatinine ratio, body mass index (BMI) and duration of DM. For the T2D group alone, there were significant associations between DR and HbA1c, BMI, urine creatinine, urine albumin-to-creatinine ratio and duration of DM. The analysis also showed three times higher odds for DR in the T1D group than the T2D group. Conclusions: This study underscores the need for implementing a systematic DR screening program in the Oslo region, Norway, to better reach out to patients with DM and improve their screening adherence. Timely and proper treatment can prevent or mitigate vision loss and improve the prognosis. A considerable number of patients were referred from general practitioners for not being followed by an ophthalmologist.Among patients not newly diagnosed with DM, 62.8% had never had an eye exam, and the duration of DM for these patients was up to 18 years (median: 8 years). Full article

(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)

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19 pages, 1032 KiB

Open AccessReview

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

by Cláudia Verdial, Isa Serrano, Luís Tavares, Solange Gil and Manuela Oliveira

Biomedicines 2023, 11(4), 1221; https://doi.org/10.3390/biomedicines11041221 - 19 Apr 2023

Cited by 19 | Viewed by 3932

Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for multiple hospital- and community-acquired infections, both in human and veterinary medicine. P. aeruginosa persistence in clinical settings is worrisome and is a result of its remarkable flexibility and adaptability. This species exhibits several characteristics [...] Read more.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for multiple hospital- and community-acquired infections, both in human and veterinary medicine. P. aeruginosa persistence in clinical settings is worrisome and is a result of its remarkable flexibility and adaptability. This species exhibits several characteristics that allow it to thrive under different environmental conditions, including the ability to colonize inert materials such as medical equipment and hospital surfaces. P. aeruginosa presents several intrinsic mechanisms of defense that allow it to survive external aggressions, but it is also able to develop strategies and evolve into multiple phenotypes to persevere, which include antimicrobial-tolerant strains, persister cells, and biofilms. Currently, these emergent pathogenic strains are a worldwide problem and a major concern. Biocides are frequently used as a complementary/combination strategy to control the dissemination of P. aeruginosa-resistant strains; however, tolerance to commonly used biocides has also already been reported, representing an impediment to the effective elimination of this important pathogen from clinical settings. This review focuses on the characteristics of P. aeruginosa responsible for its persistence in hospital environments, including those associated with its antibiotic and biocide resistance ability. Full article

(This article belongs to the Special Issue Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance)

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20 pages, 650 KiB

Open AccessReview

Physiopathology of Osteoporosis: Nursing Involvement and Management

by Sandra Valenzuela-Martínez, María Jesús Ramírez-Expósito, María Pilar Carrera-González and José Manuel Martínez-Martos

Biomedicines 2023, 11(4), 1220; https://doi.org/10.3390/biomedicines11041220 - 19 Apr 2023

Cited by 5 | Viewed by 4832

Abstract

Osteoporosis is a major public health problem today. We are facing an aging society where the average life expectancy continues to increase. Osteoporosis affects more than 30% of postmenopausal women due to hormonal changes that occur during this time. Postmenopausal osteoporosis is therefore [...] Read more.

Osteoporosis is a major public health problem today. We are facing an aging society where the average life expectancy continues to increase. Osteoporosis affects more than 30% of postmenopausal women due to hormonal changes that occur during this time. Postmenopausal osteoporosis is therefore of particular concern. The aim of this review is to identify the etiology, pathophysiology, diagnosis and treatment of this disease and lay the foundation for the role nurses should play in preventing postmenopausal osteoporosis. Several risk factors are associated with osteoporosis. In addition to age and sex, genetics, ethnicity, diet, or the presence of other disorders determine the development of this disease. The key factors include exercise, a balanced diet, and high levels of vitamin D. This is primarily from a solar source, and infancy is the time when future bone formation is greatest. There are now medications that can complement these preventive measures. The work of nursing staff is not only prevention, but also early detection and early treatment. In addition, imparting information and knowledge about the disease to the population is key to preventing an osteoporosis epidemic. In this study, a detailed description is provided of the biological and physiological disease, the preventive measures currently being researched, the information currently available to the population, and how health professionals address osteoporosis from a preventive perspective. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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19 pages, 3638 KiB

Open AccessArticle

Transcriptional Profiling of a Patient-Matched Cohort of Glioblastoma (IDH-Wildtype) for Therapeutic Target and Repurposing Drug Identification

by Aideen C. Roddy, Caitríona E. McInerney, Tom Flannery, Estelle G. Healy, James P. Stewart, Veronica J. Spence, Jamie Walsh, Manuel Salto-Tellez, Darragh G. McArt and Kevin M. Prise

Biomedicines 2023, 11(4), 1219; https://doi.org/10.3390/biomedicines11041219 - 19 Apr 2023

Cited by 2 | Viewed by 3567

Abstract

Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are [...] Read more.

Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are urgently needed to target these. The biology underpinning GBM recurrence was investigated using whole transcriptome profiling of patient-matched initial and recurrent GBM (recGBM). Differential expression analysis identified 147 significant probes. In total, 24 genes were validated using expression data from four public cohorts and the literature. Functional analyses revealed that transcriptional changes to recGBM were dominated by angiogenesis and immune-related processes. The role of MHC class II proteins in antigen presentation and the differentiation, proliferation, and infiltration of immune cells was enriched. These results suggest recGBM would benefit from immunotherapies. The altered gene signature was further analyzed in a connectivity mapping analysis with QUADrATiC software to identify FDA-approved repurposing drugs. Top-ranking target compounds that may be effective against GSC and GBM recurrence were rosiglitazone, nizatidine, pantoprazole, and tolmetin. Our translational bioinformatics pipeline provides an approach to identify target compounds for repurposing that may add clinical benefit in addition to standard therapies against resistant cancers such as GBM. Full article

(This article belongs to the Special Issue Drug Resistance and Novel Targets for Cancer Therapy)

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10 pages, 281 KiB

Open AccessArticle

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades

by Nikolett Nagy, Gábor Papp, Eszter Gáspár-Kiss, Ágnes Diószegi and Tünde Tarr

Biomedicines 2023, 11(4), 1218; https://doi.org/10.3390/biomedicines11041218 - 19 Apr 2023

Cited by 2 | Viewed by 2355

Abstract

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has [...] Read more.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

28 pages, 2012 KiB

Open AccessReview

Multi-Omics and Management of Follicular Carcinoma of the Thyroid

by Thifhelimbilu Emmanuel Luvhengo, Ifongo Bombil, Arian Mokhtari, Maeyane Stephens Moeng, Demetra Demetriou, Claire Sanders and Zodwa Dlamini

Biomedicines 2023, 11(4), 1217; https://doi.org/10.3390/biomedicines11041217 - 19 Apr 2023

Cited by 5 | Viewed by 5336

Abstract

Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are [...] Read more.

Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are modeled after those of papillary thyroid carcinoma (PTC), even though FTC is more aggressive. FTC has a greater propensity for haematogenous metastasis than PTC. Furthermore, FTC is a phenotypically and genotypically heterogeneous disease. The diagnosis and identification of markers of an aggressive FTC depend on the expertise and thoroughness of pathologists during histopathological analysis. An untreated or metastatic FTC is likely to de-differentiate and become poorly differentiated or undifferentiated and resistant to standard treatment. While thyroid lobectomy is adequate for the treatment of selected patients who have low-risk FTC, it is not advisable for patients whose tumor is larger than 4 cm in diameter or has extensive extra-thyroidal extension. Lobectomy is also not adequate for tumors that have aggressive mutations. Although the prognosis for over 80% of PTC and FTC is good, nearly 20% of the tumors behave aggressively. The introduction of radiomics, pathomics, genomics, transcriptomics, metabolomics, and liquid biopsy have led to improvements in the understanding of tumorigenesis, progression, treatment response, and prognostication of thyroid cancer. The article reviews the challenges that are encountered during the diagnostic work-up, staging, risk stratification, management, and follow-up of patients who have FTC. How the application of multi-omics can strengthen decision-making during the management of follicular carcinoma is also discussed. Full article

(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)

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29 pages, 6916 KiB

Open AccessArticle

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways

by Stanislav Kotlyarov

Biomedicines 2023, 11(4), 1216; https://doi.org/10.3390/biomedicines11041216 - 19 Apr 2023

Cited by 2 | Viewed by 2656

Abstract

(1) Background: Atherosclerosis is a serious medical condition associated with high morbidity and mortality rates. It develops over many years as a complex chain of events in the vascular wall involving various cells and is influenced by many factors of clinical interest. (2) [...] Read more.

(1) Background: Atherosclerosis is a serious medical condition associated with high morbidity and mortality rates. It develops over many years as a complex chain of events in the vascular wall involving various cells and is influenced by many factors of clinical interest. (2) Methods: In this study, we performed a bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to investigate the gene ontology of differentially expressed genes (DEGs) in endothelial cells exposed to atherogenic factors such as tobacco smoking, oscillatory shear, and oxidized low-density lipoproteins (oxLDL). DEGs were identified using the limma R package, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) network analysis were performed. (3) Results: We studied biological processes and signaling pathways involving DEGs in endothelial cells under the influence of atherogenic factors. GO enrichment analysis demonstrated that the DEGs were mainly involved in cytokine-mediated signaling pathway, innate immune response, lipid biosynthetic process, 5-lipoxygenase activity, and nitric-oxide synthase activity. KEGG pathway enrichment analysis showed that common pathways included tumor necrosis factor signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis, lipoprotein particle binding, and apoptosis. (4) Conclusions: Atherogenic factors such as smoking, impaired flow, and oxLDL contribute to impaired innate immune response, metabolism, and apoptosis in endothelial cells, potentially leading to the development of atherosclerosis. Full article

(This article belongs to the Special Issue Atherosclerotic Cardiovascular Disease (ASCVD), Dyslipidemia, and CV Residual Risk: From Mechanisms to Therapeutic Approaches 2.0)

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14 pages, 917 KiB

Open AccessReview

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

by Andrei Surguchov, Fatemeh N. Emamzadeh, Mariya Titova and Alexei A. Surguchev

Biomedicines 2023, 11(4), 1215; https://doi.org/10.3390/biomedicines11041215 - 19 Apr 2023

Cited by 15 | Viewed by 2544

Abstract

For a long time, studies of amyloidogenic proteins and peptides (amyloidogenic PPs) have been focused basically on their harmful properties and association with diseases. A vast amount of research has investigated the structure of pathogenic amyloids forming fibrous deposits within or around cells [...] Read more.

For a long time, studies of amyloidogenic proteins and peptides (amyloidogenic PPs) have been focused basically on their harmful properties and association with diseases. A vast amount of research has investigated the structure of pathogenic amyloids forming fibrous deposits within or around cells and the mechanisms of their detrimental actions. Much less has been known about the physiologic functions and beneficial properties of amyloidogenic PPs. At the same time, amyloidogenic PPs have various useful properties. For example, they may render neurons resistant to viral infection and propagation and stimulate autophagy. We discuss here some of amyloidogenic PPs’ detrimental and beneficial properties using as examples beta-amyloid (β-amyloid), implicated in the pathogenesis of Alzheimer’s disease (AD), and α-synuclein—one of the hallmarks of Parkinson’s disease (PD). Recently amyloidogenic PPs’ antiviral and antimicrobial properties have attracted attention because of the COVID-19 pandemic and the growing threat of other viral and bacterial-induced diseases. Importantly, several COVID-19 viral proteins, e.g., spike, nucleocapsid, and envelope proteins, may become amyloidogenic after infection and combine their harmful action with the effect of endogenous APPs. A central area of current investigations is the study of the structural properties of amyloidogenic PPs, defining their beneficial and harmful properties, and identifying triggers that transform physiologically important amyloidogenic PPs into vicious substances. These directions are of paramount importance during the current SARS-CoV-2 global health crisis. Full article

(This article belongs to the Special Issue Recent Advances in Understanding of the Role of Synuclein Family Members in Health and Disease Volume II)

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14 pages, 4842 KiB

Open AccessArticle

New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents

by Massimo Bortolotti, Francesco Biscotti, Andrea Zanello, Andrea Bolognesi and Letizia Polito

Biomedicines 2023, 11(4), 1214; https://doi.org/10.3390/biomedicines11041214 - 19 Apr 2023

Cited by 2 | Viewed by 2133

Abstract

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small [...] Read more.

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small molecules (such as neurotransmitters, growth factors and peptides). Some saporin-containing targeted toxins have been used for the experimental treatment of several diseases, giving very promising results. In this context, one of the reasons for the successful use of saporin lies in its resistance to proteolytic enzymes and to conjugation procedures. In this paper, we evaluated the influence of derivatization on saporin using three heterobifunctional reagents, namely 2-iminothiolane (2-IT), N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and 4-succinimidyloxycarbonyl-α-methyl-α-[2-pyridyldithio]toluene (SMPT). In order to obtain the highest number of inserted -SH groups with the lowest reduction of saporin biological activities, we assessed the residual ability of saporin to inhibit protein synthesis, to depurinate DNA and to induce cytotoxicity after derivatization. Our results demonstrate that saporin maintains an excellent resistance to derivatization processes, especially with SPDP, and permit us to define reaction conditions, in which saporin biological properties may not be altered. Therefore, these findings provide useful information for the construction of saporin-based targeted toxins, especially with small carriers. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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12 pages, 447 KiB

Open AccessReview

Antiarrhythmic Drug Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy

by Sean P. Gaine and Hugh Calkins

Biomedicines 2023, 11(4), 1213; https://doi.org/10.3390/biomedicines11041213 - 19 Apr 2023

Cited by 7 | Viewed by 3726

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable progressive myocardial disorder that predisposes patients to ventricular arrhythmias and sudden cardiac death. Antiarrhythmic medications have an important role in reducing the frequency of ventricular arrhythmias and the morbidity associated with recurrent implantable cardioverter-defibrillator (ICD) [...] Read more.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable progressive myocardial disorder that predisposes patients to ventricular arrhythmias and sudden cardiac death. Antiarrhythmic medications have an important role in reducing the frequency of ventricular arrhythmias and the morbidity associated with recurrent implantable cardioverter-defibrillator (ICD) shocks. Although several studies have examined the use of antiarrhythmic drugs in ARVC, these have been mostly retrospective in nature and inconsistent in their methodology, patient population and endpoints. Thus, current prescribing practices are largely based on expert opinion and extrapolation from other diseases. Herein, we discuss the major studies of the use of antiarrhythmics in ARVC, present the current approach employed at the Johns Hopkins Hospital and identify areas where further research is needed. Most notably, there is a great need for high-quality studies with consistent methodology and randomized controlled trial data into the use of antiarrhythmic drugs in ARVC. This would improve management of the condition and ensure antiarrhythmic prescribing is based on robust evidence. Full article

(This article belongs to the Special Issue Advanced Research in Arrhythmogenic Cardiomyopathy)

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19 pages, 3992 KiB

Open AccessArticle

The Human Extracellular Matrix Diseasome Reveals Genotype–Phenotype Associations with Clinical Implications for Age-Related Diseases

by Cyril Statzer, Karan Luthria, Arastu Sharma, Maricel G. Kann and Collin Y. Ewald

Biomedicines 2023, 11(4), 1212; https://doi.org/10.3390/biomedicines11041212 - 19 Apr 2023

Cited by 6 | Viewed by 2823

Abstract

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and aging. The analysis of these disease states is possible with the GWAS and PheWAS methodologies, and through our analysis, we aimed to explore the relationships between polymorphisms in [...] Read more.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and aging. The analysis of these disease states is possible with the GWAS and PheWAS methodologies, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of ECM polymorphisms is evident in various types of disease, particularly those in the core-matrisome genes. Our results confirm previous links to connective-tissue disorders but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Through our analysis of the drug indications for gene–disease relationships, we identify numerous targets that may be repurposed for age-related pathologies. The identification of ECM polymorphisms and their contributions to disease will play an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care. Full article

(This article belongs to the Special Issue ECM Code in Physiological and Pathological Processes)

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10 pages, 285 KiB

Open AccessArticle

Is H19 RNA a Useful Marker of Acromegaly and Its Complications? A Preliminary Study

by Małgorzata Rolla, Aleksandra Jawiarczyk-Przybyłowska, Katarzyna Kolačkov, Agnieszka Zembska and Marek Bolanowski

Biomedicines 2023, 11(4), 1211; https://doi.org/10.3390/biomedicines11041211 - 19 Apr 2023

Viewed by 1662

Abstract

Acromegaly is a rare endocrine disorder caused by somatotroph pituitary adenoma. Besides its typical symptoms, it contributes to the development of cardiovascular, metabolic, and bone comorbidities. H19 RNA is a long non-coding RNA and it is suspected to be involved in tumorigenesis, cancer [...] Read more.

Acromegaly is a rare endocrine disorder caused by somatotroph pituitary adenoma. Besides its typical symptoms, it contributes to the development of cardiovascular, metabolic, and bone comorbidities. H19 RNA is a long non-coding RNA and it is suspected to be involved in tumorigenesis, cancer progression, and metastasis. H19 RNA is a novel biomarker for the diagnosis and monitoring of neoplasms. Moreover, there might be an association between H19 and cardiovascular and metabolic diseases. We enrolled 32 acromegaly patients and 25 controls. We investigated whether whole blood H19 RNA expression is associated with the diagnosis of acromegaly. Correlations between H19 and tumour dimension, invasiveness, and biochemical and hormonal parameters were evaluated. We analysed the coincidence of acromegaly comorbidities with H19 RNA expression. In the results, we did not observe a statistically significant difference in H19 RNA expression between acromegaly patients and the controls. There were no correlations between H19 and the adenoma size and infiltration and patients’ biochemical and hormonal statuses. In the acromegaly group, hypertension, goitre, and cholelithiasis were observed more frequently. The diagnosis of acromegaly was a factor contributing to the occurrence of dyslipidaemia, goitre, and cholelithiasis. We found an association between H19 and cholelithiasis in acromegaly patients. To conclude, H19 RNA expression is not a relevant marker for diagnosis and monitoring of acromegaly patients. There is a higher risk of hypertension, goitre, and cholelithiasis related to acromegaly. Cholelithiasis is associated with a higher H19 RNA expression. Full article

(This article belongs to the Special Issue State-of-the-Art Endocrinology and Metabolism Research in Poland (Volume II))

12 pages, 302 KiB

Open AccessArticle

The Impact of Benign Jawbone Tumors on the Temporomandibular Joint and Occlusion in Children: A Ten-Year Follow-Up Study

by Emil Crasnean, Alina Ban, Raluca Roman, Cristian Dinu, Mihaela Băciuț, Vlad-Ionuț Nechita, Simion Bran, Florin Onișor, Teodora Badiu, Oana Almășan and Mihaela Hedeșiu

Biomedicines 2023, 11(4), 1210; https://doi.org/10.3390/biomedicines11041210 - 19 Apr 2023

Viewed by 1850

Abstract

This study aimed to provide a complex analysis of the modifications in craniofacial skeleton development that may arise following the diagnosis of pediatric benign jaw tumors. A prospective study was undertaken involving 53 patients younger than 18 years of age, who presented for [...] Read more.

This study aimed to provide a complex analysis of the modifications in craniofacial skeleton development that may arise following the diagnosis of pediatric benign jaw tumors. A prospective study was undertaken involving 53 patients younger than 18 years of age, who presented for treatment at the Department of Maxillo-Facial Surgery, University of Medicine and Pharmacy, Cluj-Napoca, with a primary benign jaw lesion between 2012 and 2022. A total of 28 odontogenic cysts (OCs), 14 odontogenic tumors (OTs), and 11 non-OTs were identified. At follow-up, dental anomalies were identified in 26 patients, and overjet changes were found in 33 children; lateral crossbite, midline shift, and edge-to-edge bite were found in 49 cases; deep or open bite were found in 23 patients. Temporomandibular disorders (TMDs) were found in 51 children, with unilateral TMJ changes identified in 7 cases and bilateral modifications found in 44 patients. Degenerative changes in the TMJ were also diagnosed in 22 pediatric patients. Although benign lesions could be associated with dental malocclusions, a direct etiological factor could be not identified. The presence of jaw tumors or their surgical treatment could, however, be linked to a change of the occlusal relationships or the onset of a TMD. Full article

(This article belongs to the Special Issue Progress in Biomaterials and Technologies in Dentistry)

14 pages, 592 KiB

Open AccessReview

Genome–Environment Interactions and Psychiatric Disorders

by Jacob Peedicayil

Biomedicines 2023, 11(4), 1209; https://doi.org/10.3390/biomedicines11041209 - 19 Apr 2023

Cited by 8 | Viewed by 4658

Abstract

Environmental factors are known to interact with the genome by altering epigenetic mechanisms regulating gene expression and contributing to the pathogenesis of psychiatric disorders. This article is a narrative review of how the major environmental factors contribute to the pathogenesis of common psychiatric [...] Read more.

Environmental factors are known to interact with the genome by altering epigenetic mechanisms regulating gene expression and contributing to the pathogenesis of psychiatric disorders. This article is a narrative review of how the major environmental factors contribute to the pathogenesis of common psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorder this way. The cited articles were published between 1 January 2000 and 31 December 2022 and were obtained from PubMed and Google Scholar. The search terms used were as follows: gene or genetic; genome; environment; mental or psychiatric disorder; epigenetic; and interaction. The following environmental factors were found to act epigenetically on the genome to influence the pathogenesis of psychiatric disorders: social determinants of mental health, maternal prenatal psychological stress, poverty, migration, urban dwelling, pregnancy and birth complications, alcohol and substance abuse, microbiota, and prenatal and postnatal infections. The article also discusses the ways by which factors such as drugs, psychotherapy, electroconvulsive therapy, and physical exercise act epigenetically to alleviate the symptoms of psychiatric disorders in affected patients. These data will be useful information for clinical psychiatrists and those researching the pathogenesis and treatment of psychiatric disorders. Full article

(This article belongs to the Special Issue Genome-Environment Interactions in Psychiatric Disorders and Neurodegenerative Diseases)

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19 pages, 3974 KiB

Open AccessArticle

Cyclic GMP–AMP Synthase (cGAS) Deletion Reduces Severity in Bilateral Nephrectomy Mice through Changes in Neutrophil Extracellular Traps and Mitochondrial Respiration

by Nattavong Suksawad, Kanyarat Udompornpitak, Natchapon Thawinpipat, Pichaya Korwattanamongkol, Peerapat Visitchanakun, Pornpimol Phuengmaung, Wilasinee Saisorn, Patipark Kueanjinda and Asada Leelahavanichkul

Biomedicines 2023, 11(4), 1208; https://doi.org/10.3390/biomedicines11041208 - 18 Apr 2023

Cited by 5 | Viewed by 2128

Abstract

Uremia-induced systemic inflammation is partly caused by the dissemination of microbial molecules such as lipopolysaccharide and bacterial double-stranded DNA from leaked gut damaged by immune cells in response to the microbial molecules. Cyclic GMP–AMP synthase (cGAS) can recognize fragmented DNA and induce cGAMP [...] Read more.

Uremia-induced systemic inflammation is partly caused by the dissemination of microbial molecules such as lipopolysaccharide and bacterial double-stranded DNA from leaked gut damaged by immune cells in response to the microbial molecules. Cyclic GMP–AMP synthase (cGAS) can recognize fragmented DNA and induce cGAMP synthesis for the activation of the stimulator of interferon genes (STING) pathway. To study the effect of cGAS in uremia-induced systemic inflammation, we performed bilateral nephrectomy (BNx) in wild-type and cGAS knock-out mice and found that the gut leakage and blood uremia from both groups were similar. However, serum cytokines (TNF-α and IL-6) and neutrophil extracellular traps (NETs) decreased significantly in cGAS^−/− neutrophils after stimulation with LPS or bacterial cell-free DNA. Transcriptomic analysis of LPS-stimulated cGAS^−/− neutrophils also confirmed the down-regulation of neutrophil effector functions. The extracellular flux analysis showed that cGAS^−/− neutrophils exhibited a higher respiratory rate than wild-type neutrophils despite having similar mitochondrial abundance and function. Our results suggest that cGAS may control effector functions and the mitochondrial respiration of neutrophils in response to LPS or bacterial DNA. Full article

(This article belongs to the Special Issue Sepsis: From Pathophysiology to Novel Therapeutic Approach)

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11 pages, 3316 KiB

Open AccessReview

Cheek-Pro-Heart: What Can the Buccal Mucosa Do for Arrhythmogenic Cardiomyopathy?

by Carlos Bueno-Beti and Angeliki Asimaki

Biomedicines 2023, 11(4), 1207; https://doi.org/10.3390/biomedicines11041207 - 18 Apr 2023

Viewed by 1850

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease associated with ventricular arrhythmias and a high risk of sudden cardiac death (SCD). Although the disease was described over 40 years ago, its diagnosis is still difficult. Several studies have identified a set of five [...] Read more.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease associated with ventricular arrhythmias and a high risk of sudden cardiac death (SCD). Although the disease was described over 40 years ago, its diagnosis is still difficult. Several studies have identified a set of five proteins (plakoglobin, Cx43, Nav1.5, SAP97 and GSK3β), which are consistently re-distributed in myocardial samples from ACM patients. Not all protein shifts are specific to ACM, but their combination has provided us with a molecular signature for the disease, which has greatly aided post-mortem diagnosis of SCD victims. The use of this signature, however, was heretofore restricted in living patients, as the analysis requires a heart sample. Recent studies have shown that buccal cells behave similarly to the heart in terms of protein re-localization. Protein shifts are associated with disease onset, deterioration and favorable response to anti-arrhythmic therapy. Accordingly, buccal cells can be used as a surrogate for the myocardium to aid diagnosis, risk stratification and even monitor response to pharmaceutical interventions. Buccal cells can also be kept in culture, hence providing an ex vivo model from the patient, which can offer insights into the mechanisms of disease pathogenesis, including drug response. This review summarizes how the cheek can aid the heart in the battle against ACM. Full article

(This article belongs to the Special Issue Advanced Research in Arrhythmogenic Cardiomyopathy)

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