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Biomedicines
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State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition
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State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 7598

Special Issue Editors

Dr. Małgorzata Wrzosek

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Guest Editor
Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Banacha St. 1, 02-097 Warsaw, Poland
Interests: biochemistry and molecular medicine; pharmacogenomics and nutrigenomics; molecular and cellular mechanisms of disease pathogenesis; personalized patient care; biomarkers of disease: a proteomics approach, assessment of therapy effectiveness; obesity, cancer and inflammation; metabolic disease and adipose tissue biology in patients undergoing bariatric surgery, toxicology, neuroscience, immunology and microbiology
Special Issues, Collections and Topics in MDPI journals
Dr. Arkadiusz Kocur

E-Mail Website
Guest Editor
1. Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland
2. Therapeutic Drug Monitoring, Clinical Pharmacokinetics and Toxicology Laboratory Unit, Department of Clinical Biochemistry, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
Interests: therapeutic drug monitoring; toxicology; pharmacokinetics; PK/PD modelling; sepsis; infectious diseases; microbiology; pathogens resistance; immunosuppressive therapy; personalized patient healthcare; pharmacogenomics; metabolomics; biomarkers of diseases; alternative sampling strategies; microsampling; personalized therapy in oncology

Special Issue Information

Dear Colleagues,

New therapeutic approaches require the knowledge and skills of multiple disciplines. The comprehensive exploration of biological mechanisms and the molecular pathogenesis of major human diseases enables personalized treatment. The integration of omics approaches in combination with modeling approaches and systems biology may play a crucial role in establishing novel clinical applications. Furthermore, the sequencing of individual human genomes has provided an opportunity to develop pharmacogenetics in routine medical practice in order to avoid side effects, and choose the most effective drug and dose according to each individual genotype.

For this Special Issue, we seek papers focused on the mechanisms associated with the development of diseases, including cell-to-cell metabolic crosstalk in physiology, pathology and cancer research. New insights into the molecular mechanisms related to therapy effectiveness and changes in gene expression that have important implications for understanding genotype–phenotype maps are also of importance. There is no doubt that further knowledge is required for the future development of clinically relevant guidelines and new methods for the early detection, prevention, treatment and prognosis of diseases.

Dr. Małgorzata Wrzosek
Dr. Arkadiusz Kocur
Guest Editors

Manuscript Submission Information

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

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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 2600 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

  • molecular medicine
  • molecular mechanisms
  • disease pathogenesis
  • genetic variants
  • gene expression
  • epigenetics
  • metabolic disorders
  • cancer

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Published Papers (5 papers)

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Research

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17 pages, 3382 KiB  
Communication
Progressive Cachexia: Tuberculosis, Cancer, or Thyrotoxicosis? Disease-Directed Therapy and Atypical Courses of Autoimmune and Malignant Thyroid Diseases in a High Specialization Era: Case-Control Study with a Critical Literature Review
by Przemyslaw Zdziarski and Zbigniew Sroka
Biomedicines 2024, 12(12), 2722; https://doi.org/10.3390/biomedicines12122722 - 28 Nov 2024
Viewed by 1221
Abstract
Background. Critical and progressive cachexia may be observed in numerous medical disciplines, but in patients with various diseases, several pathways overlap (endocrine, inflammatory and kidney diseases, heart failure, cancer). Methods. Unlike numerous cohort studies that examine thyroid cancer and risk factors, a different [...] Read more.
Background. Critical and progressive cachexia may be observed in numerous medical disciplines, but in patients with various diseases, several pathways overlap (endocrine, inflammatory and kidney diseases, heart failure, cancer). Methods. Unlike numerous cohort studies that examine thyroid cancer and risk factors, a different method was used to avoid bias and analyze the sequence of events, i.e., the pathway. A case-control analysis is presented on patients with initial immune-mediated thyroiditis complicated by cachexia, presenting pulmonary pathology coexisting with opportunistic infection, and ultimately diagnosed with cancer (TC—thyroid cancer, misdiagnosed as lung cancer). Results. Contrary to other patients with lung cancer, the presented patients were not active smokers and exclusively women who developed cachexia with existing autoimmune processes in the first phase. Furthermore, the coexistence of short overall survival without cancer progression in the most seriously ill patients, as well as correlation with sex (contrary to history of smoking) and predisposition to mycobacterial disease, are very suggestive. Although we describe three different autoimmune conditions (de Quervain’s, Graves’, and atrophic thyroiditis), disturbances in calcium and metabolic homeostasis, under the influence of hormonal and inflammatory changes, are crucial factors of cachexia and prognosis. Conclusions. The unique sequence sheds light on immune-mediated thyroid disease as a subclinical paraneoplastic process modified by various therapeutic regimens. However, it is also associated with cachexia, systemic consequences, and atypical sequelae, which require a holistic approach. The differential diagnosis of severe cachexia, adenocarcinoma with pulmonary localization, and tuberculosis reactivation requires an analysis of immunological and genetic backgrounds. Contrary to highly specialized teams (e.g., lung cancer units), immunotherapy and general medicine in aging populations require a multidisciplinary, holistic, and inquiring approach. The lack of differentiation, confusing biases, and discrepancies in the literature are the main obstacles to statistical research, limiting findings to correlations of common factors only. Time-lapse case studies such as this one may be among the first to build evidence of a pathway and an association between inflammatory and endocrine imbalances in cancer cachexia. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition)
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14 pages, 678 KiB  
Article
Predictive and Prognostic Role of Systemic Immune-Inflammation Index (SII) in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil
by Mateusz Malik, Barbara Radecka, Marek Gełej, Aleksandra Jackowska, Emilia Filipczyk-Cisarż, Michalina Żurowska, Katarzyna Hetman, Małgorzata Foszczyńska-Kłoda, Beata Kania-Zembaczyńska, Danuta Mańka, Marlena Orlikowska and Lubomir Bodnar
Biomedicines 2024, 12(9), 2076; https://doi.org/10.3390/biomedicines12092076 - 11 Sep 2024
Viewed by 1142
Abstract
In advanced-stage colorectal cancer (CRC), a strategy based on a sequence of systemic therapies brings survival benefits in most patients. Trifluridine and tipiracil hydrochloride (TT) is a chemotherapy drug effective in patients in the third- or later line setting. No highly specific biomarkers [...] Read more.
In advanced-stage colorectal cancer (CRC), a strategy based on a sequence of systemic therapies brings survival benefits in most patients. Trifluridine and tipiracil hydrochloride (TT) is a chemotherapy drug effective in patients in the third- or later line setting. No highly specific biomarkers have been established for TT therapy so far. However, a systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts is applied to predict prognosis. In this retrospective, multicenter study, clinical data on 179 metastatic CRC patients treated with TT were collected. To evaluate factors predicting TT therapy response and overall survival, univariate logistic regression analysis was conducted. Subsequently, factors with p < 0.05 in univariate analysis were included in multivariate analysis. In the multivariate analysis of progression-free survival (PFS), three favorable parameters were significant: good to moderate histological differentiation (p = 0.0038), carcinoembryonic antigen (CEA) < 5 ng/L (p = 0.0316) and SII ≤ 550 (p = 0.007). Favorable prognostic factors revealed in the multivariate analysis of overall survival (OS) were: <3 prior lines of treatment (p = 0.02), good to moderate histological differentiation (p = 0.0003), CEA < 5 ng/L (p = 0.0227) and SII ≤ 550 (p = 0.0001). Our study indicated that pre-treatment SII may be clinically useful for selecting likely responder patients and assessing the prognosis for mCRC patients treated with TT. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition)
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17 pages, 2310 KiB  
Article
The Strong Activation of p53 Tumor Suppressor Drives the Synthesis of the Enigmatic Isoform of DUSP13 Protein
by Małgorzata Krześniak, Barbara Łasut-Szyszka, Agnieszka Będzińska, Agnieszka Gdowicz-Kłosok and Marek Rusin
Biomedicines 2024, 12(7), 1449; https://doi.org/10.3390/biomedicines12071449 - 28 Jun 2024
Viewed by 1092
Abstract
The p53 tumor suppressor protein activates various sets of genes depending on its covalent modifications, which are controlled by the nature and intensity of cellular stress. We observed that actinomycin D and nutlin-3a (A + N) collaborate in inducing activating phosphorylation of p53. [...] Read more.
The p53 tumor suppressor protein activates various sets of genes depending on its covalent modifications, which are controlled by the nature and intensity of cellular stress. We observed that actinomycin D and nutlin-3a (A + N) collaborate in inducing activating phosphorylation of p53. Our recent transcriptomic data demonstrated that these substances strongly synergize in the upregulation of DUSP13, a gene with an unusual pattern of expression, coding for obscure phosphatase having two isoforms, one expressed in the testes and the other in skeletal muscles. In cancer cells exposed to A + N, DUSP13 is expressed from an alternative promoter in the intron, resulting in the expression of an isoform named TMDP-L1. Luciferase reporter tests demonstrated that this promoter is activated by both endogenous and ectopically expressed p53. We demonstrated for the first time that mRNA expressed from this promoter actually produces the protein, which can be detected with Western blotting, in all examined cancer cell lines with wild-type p53 exposed to A + N. In some cell lines, it is also induced by clinically relevant camptothecin, by nutlin-3a acting alone, or by a combination of actinomycin D and other antagonists of p53-MDM2 interaction—idasanutlin or RG7112. This isoform, fused with green fluorescent protein, localizes in the perinuclear region of cells. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition)
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Review

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13 pages, 829 KiB  
Review
Peptide-Based Inhibitors of Protein–Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2)
by Aizhan Rakhmetullina, Piotr Zielenkiewicz and Norbert Odolczyk
Biomedicines 2024, 12(10), 2361; https://doi.org/10.3390/biomedicines12102361 - 16 Oct 2024
Cited by 2 | Viewed by 1352
Abstract
Protein–protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme [...] Read more.
Protein–protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (hACE2), which initiates a series of events leading to viral replication. Interrupting this interaction offers a promising strategy for blocking or significantly reducing infection, highlighting its potential as a target for anti-SARS-CoV-2 therapies. This review focuses on the hACE2 and SARS-CoV-2 spike protein interaction, exemplifying the latest advancements in peptide-based strategies for developing PPI inhibitors. We discuss various approaches for creating peptide-based inhibitors that target this critical interaction, aiming to provide potential treatments for COVID-19. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition)
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25 pages, 1837 KiB  
Review
Gas Chromatography–Mass Spectrometry-Based Analyses of Fecal Short-Chain Fatty Acids (SCFAs): A Summary Review and Own Experience
by Paweł Czarnowski, Michał Mikula, Jerzy Ostrowski and Natalia Żeber-Lubecka
Biomedicines 2024, 12(8), 1904; https://doi.org/10.3390/biomedicines12081904 - 20 Aug 2024
Cited by 2 | Viewed by 2062
Abstract
The gut microbiome, crucial to human health, changes with age and disease, and influences metabolic profiles. Gut bacteria produce short-chain fatty acids (SCFAs), essential for maintaining homeostasis and modulating inflammation. Dysbiosis, commonly due to poor diet or lifestyle, disrupts the integrity of the [...] Read more.
The gut microbiome, crucial to human health, changes with age and disease, and influences metabolic profiles. Gut bacteria produce short-chain fatty acids (SCFAs), essential for maintaining homeostasis and modulating inflammation. Dysbiosis, commonly due to poor diet or lifestyle, disrupts the integrity of the intestinal barrier and may contribute to conditions such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Analytical methods such as gas chromatography–mass spectrometry (GC/MS) are vital for SCFA analysis, with various preparation and storage techniques improving the accuracy. Advances in these methods have improved the reliability and sensitivity of SCFA quantification, which is crucial for the identification of disease biomarkers. Evidence from GC/MS-based studies has revealed that accurate SCFA quantification requires meticulous sample preparation and handling. The process begins with the extraction of SCFAs from biological samples using methods such as direct solvent extraction or solid-phase microextraction (SPME), both of which require optimization for maximum recovery. Derivatization, which chemically modifies SCFAs to enhance volatility and detectability, is a crucial step, typically involving esterification or silylation. Following this, the cleanup process removes impurities that might interfere with the analysis. Although recent advances in GC/MS technology have significantly improved SCFA-detection sensitivity and specificity, proper sample storage, with acid preservatives and the avoidance of repeated thawing, is essential for maintaining SCFA integrity. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular and Translational Medicine in Poland, 3rd Edition)
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