10th Anniversary of Biomolecules—Advances in Biomarkers, Therapeutics and Prevention

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 30139

Special Issue Editor

Research institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
Interests: Biomarkers and therapeutics; Cell function and fate; Liver, gut and neurodegenerative diseases; Molecular targets
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This year marks the 10th anniversary of the open access MDPI journal Biomolecules. To celebrate this important occasion, we are delighted and proud to celebrate with a series of Special Issues and events. As of 10 August 2020, the journal has received more than 6,000 contributions and published more than 2,600 articles, and the journal website attracts more than 26,483 monthly page views. We would like to express our sincerest thanks to our readers, innumerable authors, anonymous peer reviewers, editors, and all the people working in some way for the journal who have made substantial contributions for years. Without your support, we would never have made it.

To mark this important milestone, a Special Issue entitled “10th Anniversary of Biomolecules—Recent Advances in Biomarkers, Therapeutics and Prevention” is being launched. This Special Issue will collect research articles, and high-quality review papers in the research fields relating to biomarkers. We encourage research groups working in various areas of biomarkers to make contributions to this Special Issue.

A scientific journal is the collaborative achievement of many scientists from all over the world and we would like to thank all our authors and reviewers who have contributed to the Special Issue. In recognition of our authors’ continued support, Biomolecules is pleased to announce that the “Biomolecules Best Paper Awards for Anniversary Special Issues” will be launched and granted to the best papers published in the Anniversary Special Issues. See the details at the following link:

https://0-www-mdpi-com.brum.beds.ac.uk/journal/biomolecules/awards

The Ph D. Advanced Course “Molecular Biomarkers and Technologies” held at the Faculty of Pharmacy, University of Lisbon, from 20th to 24th September 2021, is designed to cover principles and applications of biomarkers and technologies, from identification to validation, to impact in drug discovery and in disease diagnosis, prognosis and treatment. The program will cover the latest advances in clinical and translational biomarkers as well as the new frontier of digital biomarkers and their impact on drug discovery and diagnostics. This course will be taught in English and delivered completely online (through the Zoom platform). See further information at the following link:

https://www.ff.ulisboa.pt/doutoramento-em-farmacia/phd-advanced-courseamolecular-biomarkers-and-technologies/?lang=en

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Prof. Dr. Cecilia Rodrigues
Guest Editor

Manuscript Submission Information

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

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biomarkers in preventive medicine
  • Biomarkers in diagnosis
  • Biomarkers in therapeutics and prognosis
  • Biomarkers in clinical trials and drug discovery
  • Technologies and omics

Published Papers (10 papers)

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Research

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14 pages, 1823 KiB  
Article
Searching for Noninvasive Predictors of the Diagnosis and Monitoring of Eosinophilic Esophagitis—The Importance of Biomarkers of the Inflammatory Reaction Involving Eosinophils
by Joanna Sarbinowska, Benita Wiatrak and Dorota Waśko-Czopnik
Biomolecules 2021, 11(6), 890; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11060890 - 15 Jun 2021
Cited by 8 | Viewed by 2779
Abstract
Background: Invasive and costly endoscopic diagnosis is obligatory for the diagnosis and monitoring of eosinophilic esophagitis (EoE). This study aims to evaluate the usefulness of serum biomarkers involved in eosinophil-mediated inflammation in the management of EoE. Methods: A prospective cohort study was conducted [...] Read more.
Background: Invasive and costly endoscopic diagnosis is obligatory for the diagnosis and monitoring of eosinophilic esophagitis (EoE). This study aims to evaluate the usefulness of serum biomarkers involved in eosinophil-mediated inflammation in the management of EoE. Methods: A prospective cohort study was conducted in 58 patients with dysphagia. Each participant completed a health questionnaire, underwent esophagogastroduodenoscopy with esophageal biopsy for histopathological examination and assessment of total, inflammatory and fibrostenotic Eosinophilic Esophagitis Reference Score (EREFS). Serum levels of interleukin 5 (IL-5), interleukin 13 (IL-13), transforming growth factor β1 (TGF-β1), major basic protein (MBP), and eotaxin 3 were determined by enzyme immunoassays. Total of 16 patients meeting the histological criteria for EoE were treated with proton pump inhibitors for 8 weeks, and then the same diagnostics was performed again. Results: Statistically significantly higher concentrations of MBP and TGF-β1 were demonstrated in the group of patients with EoE, while MBP and eotaxin 3 correlated with the peak eosinophil count (PEC). Baseline MBP levels and eotaxin 3 after treatment significantly positively correlated with EREFS. There was a negative correlation between IL-13 and fibrostenotic EREFS. Additionally, after treatment, a negative correlation TGF-β1 was noted with the inflammatory EREFS and a positive correlation with the fibrostenotic EREFS. Conclusions: The potential role of MBP in predicting the diagnosis of EoE, eotaxin 3 in predicting the advancement and correlation of IL-13 and TGF-β1 in differentiating the inflammatory and fibrotic course of the disease may facilitate the management and individualization of EoE therapy. Full article
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15 pages, 1537 KiB  
Article
The Influence of rs1859168 Polymorphism on Serum Expression of HOTTIP and Its Target miR-615-3p in Egyptian Patients with Breast Cancer
by Omayma O. Abdelaleem, Olfat G. Shaker, Marwa N. AbdelHafez, Noha K. Abdelghaffar, Hanaa M. Eid, Mohamed Zaidan, Abeer A. Khalefa, Naglaa A. Ahmed, Nada F. Hemeda, Othman M. Zaki, Aeshah Ali A. Awaji and Shereen R. Mohammed
Biomolecules 2021, 11(5), 733; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050733 - 14 May 2021
Cited by 9 | Viewed by 1983
Abstract
Background: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the [...] Read more.
Background: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). Methods: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. Results: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). Conclusions: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC. Full article
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14 pages, 2680 KiB  
Article
Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia
by Anna Tkachev, Elena Stekolshchikova, Nickolay Anikanov, Svetlana Zozulya, Aleksandra Barkhatova, Tatiana Klyushnik and Daria Petrova
Biomolecules 2021, 11(5), 720; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050720 - 11 May 2021
Cited by 4 | Viewed by 3822
Abstract
Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of [...] Read more.
Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma. Full article
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18 pages, 4031 KiB  
Article
Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma
by Joana Lopes, Tânia Ferreira-Gonçalves, Isabel V. Figueiredo, Cecília M. P. Rodrigues, Hugo Ferreira, David Ferreira, Ana S. Viana, Pedro Faísca, Maria Manuela Gaspar, João M. P. Coelho, Catarina Oliveira Silva and Catarina Pinto Reis
Biomolecules 2021, 11(4), 511; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11040511 - 30 Mar 2021
Cited by 15 | Viewed by 2832
Abstract
The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed [...] Read more.
The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma. Full article
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Review

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17 pages, 2276 KiB  
Review
The Multifaceted Role of Aquaporin-9 in Health and Its Potential as a Clinical Biomarker
by Inês V. da Silva, Sabino Garra, Giuseppe Calamita and Graça Soveral
Biomolecules 2022, 12(7), 897; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12070897 - 27 Jun 2022
Cited by 21 | Viewed by 2527
Abstract
Aquaporins (AQPs) are transmembrane channels essential for water, energy, and redox homeostasis, with proven involvement in a variety of pathophysiological conditions such as edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions. The 13 AQPs present in humans are widely [...] Read more.
Aquaporins (AQPs) are transmembrane channels essential for water, energy, and redox homeostasis, with proven involvement in a variety of pathophysiological conditions such as edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions. The 13 AQPs present in humans are widely distributed in all body districts, drawing cell lineage-specific expression patterns closely related to cell native functions. Compelling evidence indicates that AQPs are proteins with great potential as biomarkers and targets for therapeutic intervention. Aquaporin-9 (AQP9) is the most expressed in the liver, with implications in general metabolic and redox balance due to its aquaglyceroporin and peroxiporin activities, facilitating glycerol and hydrogen peroxide (H2O2) diffusion across membranes. AQP9 is also expressed in other tissues, and their altered expression is described in several human diseases, such as liver injury, inflammation, cancer, infertility, and immune disorders. The present review compiles the current knowledge of AQP9 implication in diseases and highlights its potential as a new biomarker for diagnosis and prognosis in clinical medicine. Full article
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26 pages, 1472 KiB  
Review
Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data
by Joana S. Vital, Luís Tanoeiro, Ricardo Lopes-Oliveira and Filipa F. Vale
Biomolecules 2022, 12(5), 691; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050691 - 11 May 2022
Cited by 14 | Viewed by 3592
Abstract
The Gram-negative bacterium Helicobacter pylori colonizes c.a. 50% of human stomachs worldwide and is the major risk factor for gastric adenocarcinoma. Its high genetic variability makes it difficult to identify biomarkers of early stages of infection that can reliably predict its outcome. Moreover, [...] Read more.
The Gram-negative bacterium Helicobacter pylori colonizes c.a. 50% of human stomachs worldwide and is the major risk factor for gastric adenocarcinoma. Its high genetic variability makes it difficult to identify biomarkers of early stages of infection that can reliably predict its outcome. Moreover, the increasing antibiotic resistance found in H. pylori defies therapy, constituting a major human health problem. Here, we review H. pylori virulence factors and genes involved in antibiotic resistance, as well as the technologies currently used for their detection. Furthermore, we show that next generation sequencing may lead to faster characterization of virulence factors and prediction of the antibiotic resistance profile, thus contributing to personalized treatment and management of H. pylori-associated infections. With this new approach, more and permanent data will be generated at a lower cost, opening the future to new applications for H. pylori biomarker identification and antibiotic resistance prediction. Full article
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17 pages, 2520 KiB  
Review
Novel Approaches to an Integrated Route for Trisomy 21 Evaluation
by Angelika Buczyńska, Iwona Sidorkiewicz, Anna Trochimiuk, Sławomir Ławicki, Adam Jacek Krętowski and Monika Zbucka-Krętowska
Biomolecules 2021, 11(9), 1328; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11091328 - 08 Sep 2021
Cited by 3 | Viewed by 2861
Abstract
Trisomy 21 (T21) is one of the most commonly occurring genetic disorders, caused by the partial or complete triplication of chromosome 21. Despite the significant progress in the diagnostic tools applied for prenatal screening, commonly used methods are still imprecise and involve invasive [...] Read more.
Trisomy 21 (T21) is one of the most commonly occurring genetic disorders, caused by the partial or complete triplication of chromosome 21. Despite the significant progress in the diagnostic tools applied for prenatal screening, commonly used methods are still imprecise and involve invasive diagnostic procedures that are related to a maternal risk of miscarriage. In this case, novel prenatal biomarkers are still being evaluated using highly specialized techniques, which could increase the diagnostic usefulness of biochemical prenatal screening for T21. From the other hand, the T21′s pathogenesis, caused by the improper division of genetic material, disrupting many metabolic pathways, could be further evaluated with the use of omics methods, which could result in bringing relevant insights for the evaluation of potential medical targets. Accordingly, a literature search was undertaken to collect novel information about prenatal screening for Down syndrome with the use of advanced technology, with a particular emphasis on the evaluation of novel screening biomarkers and the discovery of potential medical targets. These meta-analyses are focused on novel approaches designed with the use of omics techniques, representing the most rapidly developing and promising field in research today. Considering the limitations and progress of these methods, the use of omics techniques in evaluating T21 pathogenesis could bring beneficial results in prenatal screening, simultaneously uncovering novel potential medical targets. Full article
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24 pages, 1380 KiB  
Review
Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis
by Junya Ono, Masayuki Takai, Ayami Kamei, Yoshinori Azuma and Kenji Izuhara
Biomolecules 2021, 11(8), 1084; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081084 - 22 Jul 2021
Cited by 9 | Viewed by 3317
Abstract
Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management [...] Read more.
Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions. Full article
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18 pages, 2234 KiB  
Review
Centrosome Dynamics and Its Role in Inflammatory Response and Metastatic Process
by Massimo Pancione, Luigi Cerulo, Andrea Remo, Guido Giordano, Álvaro Gutierrez-Uzquiza, Paloma Bragado and Almudena Porras
Biomolecules 2021, 11(5), 629; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050629 - 23 Apr 2021
Cited by 4 | Viewed by 3369
Abstract
Metastasis is a process by which cancer cells escape from the location of the primary tumor invading normal tissues at distant organs. Chromosomal instability (CIN) is a hallmark of human cancer, associated with metastasis and therapeutic resistance. The centrosome plays a major role [...] Read more.
Metastasis is a process by which cancer cells escape from the location of the primary tumor invading normal tissues at distant organs. Chromosomal instability (CIN) is a hallmark of human cancer, associated with metastasis and therapeutic resistance. The centrosome plays a major role in organizing the microtubule cytoskeleton in animal cells regulating cellular architecture and cell division. Loss of centrosome integrity activates the p38-p53-p21 pathway, which results in cell-cycle arrest or senescence and acts as a cell-cycle checkpoint pathway. Structural and numerical centrosome abnormalities can lead to aneuploidy and CIN. New findings derived from studies on cancer and rare genetic disorders suggest that centrosome dysfunction alters the cellular microenvironment through Rho GTPases, p38, and JNK (c-Jun N-terminal Kinase)-dependent signaling in a way that is favorable for pro-invasive secretory phenotypes and aneuploidy tolerance. We here review recent data on how centrosomes act as complex molecular platforms for Rho GTPases and p38 MAPK (Mitogen activated kinase) signaling at the crossroads of CIN, cytoskeleton remodeling, and immune evasion via both cell-autonomous and non-autonomous mechanisms. Full article
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Other

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9 pages, 671 KiB  
Commentary
Plasmalemmal V-ATPase as a Potential Biomarker for Lactoferrin-Based Anticancer Therapy
by Cátia Santos-Pereira, Lígia R. Rodrigues and Manuela Côrte-Real
Biomolecules 2022, 12(1), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12010119 - 12 Jan 2022
Cited by 5 | Viewed by 1776
Abstract
Lactoferrin (Lf) is a milk-derived protein with well-recognized potential as a therapeutic agent against a wide variety of cancers. This natural protein exhibits health-promoting effects and has several interesting features, including its selectivity towards cancer cells, good tolerability in humans, worldwide availability, and [...] Read more.
Lactoferrin (Lf) is a milk-derived protein with well-recognized potential as a therapeutic agent against a wide variety of cancers. This natural protein exhibits health-promoting effects and has several interesting features, including its selectivity towards cancer cells, good tolerability in humans, worldwide availability, and holding a generally recognized as safe (GRAS) status. To prompt the rational clinical application of this promising anticancer compound, previous works aimed to unveil the molecular mechanisms underlying its selective anticancer activity, where plasmalemmal V-ATPase was identified as an Lf target in cancer cells. V-ATPase is a proton pump critical for cellular homeostasis that migrates to the plasma membrane of highly metastatic cancer cells contributing to the acidity of the tumor microenvironment. Cancer cells were found to be susceptible to Lf only when this proton pump is present at the plasma membrane. Plasmalemmal V-ATPase can thus be an excellent biomarker for driving treatment decisions and forecasting clinical outcomes of Lf-based anticancer strategies. Future research endeavors should thus seek to validate this biomarker by thorough preclinical and clinical studies, as well as to develop effective methods for its detection under clinical settings. Full article
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