Journal Description
Biomedicines
Biomedicines
is an international, peer-reviewed, open access journal on biomedicines published monthly online by MDPI. The Society for Regenerative Medicine (Russian Federation) (RPO) is affiliated with Biomedicines and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q2 (Medicine (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.4 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Biomedicines include: IJTM, BioMed, Anesthesia Research and Emergency Care and Medicine.
Impact Factor:
4.7 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Exploring the Impact of Irradiation on Glioblastoma Blood-Brain-Barrier Permeability: Insights from Dynamic-Contrast-Enhanced-MRI and Histological Analysis
Biomedicines 2024, 12(5), 1091; https://doi.org/10.3390/biomedicines12051091 (registering DOI) - 14 May 2024
Abstract
(1) Background: Glioblastoma (GB) presents a formidable challenge in neuro-oncology due to its aggressive nature, limited treatment options, and poor prognosis. The blood–brain barrier (BBB) complicates treatment by hindering drug delivery to the tumor site, particularly to the infiltrative cells in the margin
[...] Read more.
(1) Background: Glioblastoma (GB) presents a formidable challenge in neuro-oncology due to its aggressive nature, limited treatment options, and poor prognosis. The blood–brain barrier (BBB) complicates treatment by hindering drug delivery to the tumor site, particularly to the infiltrative cells in the margin of the tumor, which are mainly responsible for tumor recurrence. Innovative strategies are therefore needed to enhance drug delivery in the margins of the tumor. This study explores whether irradiation can enhance BBB permeability by assessing hemodynamic changes and the distribution of contrast agents in the core and the margins of GB tumors. (2) Methods: Mice grafted with U-87MG cells were exposed to increasing irradiation doses. The distribution of contrast agents and hemodynamic parameters was evaluated using both non-invasive magnetic resonance imaging (MRI) techniques with gadolinium–DOTA as a contrast agent and invasive histological analysis with Evans blue, a fluorescent vascular leakage marker. Diffusion–MRI was also used to assess cytotoxic effects. (3) Results: The histological study revealed a complex dose-dependent effect of irradiation on BBB integrity, with increased vascular leakage at 5 Gy but reduced leakage at higher doses (10 and 15 Gy). However, there was no significant increase in the diffusion of Gd-DOTA outside the tumor area by MRI. (4) Conclusions: The increase in BBB permeability could be an interesting approach to enhance drug delivery in glioblastoma margins for low irradiation doses. In this model, DCE-MRI analysis was of limited value in assessing the BBB opening in glioblastoma after irradiation.
Full article
(This article belongs to the Special Issue Glioblastoma: Current Status and Future Prospects)
►
Show Figures
Open AccessReview
Unlocking the Future of Periodontal Regeneration: An Interdisciplinary Approach to Tissue Engineering and Advanced Therapeutics
by
Tsung-Hsi Huang, Jui-Yi Chen, Wei-Hsin Suo, Wen-Rou Shao, Chih-Ying Huang, Ming-Tse Li, Yu-Ying Li, Yuan-Hong Li, En-Lun Liang, Yu-Hsu Chen and I-Ta Lee
Biomedicines 2024, 12(5), 1090; https://doi.org/10.3390/biomedicines12051090 - 14 May 2024
Abstract
Periodontal defects present a significant challenge in dentistry, necessitating innovative solutions for comprehensive regeneration. Traditional restoration methods have inherent limitations in achieving complete and functional periodontal tissue reconstruction. Tissue engineering, a multidisciplinary approach integrating cells, biomaterials, and bioactive factors, holds tremendous promise in
[...] Read more.
Periodontal defects present a significant challenge in dentistry, necessitating innovative solutions for comprehensive regeneration. Traditional restoration methods have inherent limitations in achieving complete and functional periodontal tissue reconstruction. Tissue engineering, a multidisciplinary approach integrating cells, biomaterials, and bioactive factors, holds tremendous promise in addressing this challenge. Central to tissue engineering strategies are scaffolds, pivotal in supporting cell behavior and orchestrating tissue regeneration. Natural and synthetic materials have been extensively explored, each offering unique advantages in terms of biocompatibility and tunable properties. The integration of growth factors and stem cells further amplifies the regenerative potential, contributing to enhanced tissue healing and functional restoration. Despite significant progress, challenges persist. Achieving the seamless integration of regenerated tissues, establishing proper vascularization, and developing biomimetic scaffolds that faithfully replicate the natural periodontal environment are ongoing research endeavors. Collaborative efforts across diverse scientific disciplines are essential to overcoming these hurdles. This comprehensive review underscores the critical need for continued research and development in tissue engineering strategies for periodontal regeneration. By addressing current challenges and fostering interdisciplinary collaborations, we can unlock the full regenerative potential, paving the way for transformative advancements in periodontal care. This research not only enhances our understanding of periodontal tissues but also offers innovative approaches that can revolutionize dental therapies, improving patient outcomes and reshaping the future of periodontal treatments.
Full article
(This article belongs to the Special Issue Relationship between Periodontal Disease and Systemic Disease)
Open AccessArticle
Senescent Macrophages Release Inflammatory Cytokines and RNA-Loaded Extracellular Vesicles to Circumvent Fibroblast Senescence
by
Camille Laliberté, Bianca Bossé, Véronique Bourdeau, Luis I. Prieto, Genève Perron-Deshaies, Nhung Vuong-Robillard, Sebastian Igelmann, Lisbeth Carolina Aguilar, Marlene Oeffinger, Darren J. Baker, Luc DesGroseillers and Gerardo Ferbeyre
Biomedicines 2024, 12(5), 1089; https://doi.org/10.3390/biomedicines12051089 - 14 May 2024
Abstract
Senescent cells, which accumulate with age, exhibit a pro-inflammatory senescence-associated secretory phenotype (SASP) that includes the secretion of cytokines, lipids, and extracellular vesicles (EVs). Here, we established an in vitro model of senescence induced by Raf-1 oncogene in RAW 264.7 murine macrophages (MΦ)
[...] Read more.
Senescent cells, which accumulate with age, exhibit a pro-inflammatory senescence-associated secretory phenotype (SASP) that includes the secretion of cytokines, lipids, and extracellular vesicles (EVs). Here, we established an in vitro model of senescence induced by Raf-1 oncogene in RAW 264.7 murine macrophages (MΦ) and compared them to senescent MΦ found in mouse lung tumors or primary macrophages treated with hydrogen peroxide. The transcriptomic analysis of senescent MΦ revealed an important inflammatory signature regulated by NFkB. We observed an increased secretion of EVs in senescent MΦ, and these EVs presented an enrichment for ribosomal proteins, major vault protein, pro-inflammatory miRNAs, including miR-21a, miR-155, and miR-132, and several mRNAs. The secretion of senescent MΦ allowed senescent murine embryonic fibroblasts to restart cell proliferation. This antisenescence function of the macrophage secretome may explain their pro-tumorigenic activity and suggest that senolytic treatment to eliminate senescent MΦ could potentially prevent these deleterious effects.
Full article
(This article belongs to the Special Issue Cellular Senescence: Recent Advances and Discoveries)
►▼
Show Figures
Figure 1
Open AccessReview
Affibody PET Imaging of HER2-Expressing Cancers as a Key to Guide HER2-Targeted Therapy
by
Nina Eissler, Renske Altena, Ali Alhuseinalkhudhur, Olga Bragina, Joachim Feldwisch, Guido Wuerth, Annika Loftenius, Nikolai Brun, Rimma Axelsson, Vladimir Tolmachev, Jens Sörensen and Fredrik Y. Frejd
Biomedicines 2024, 12(5), 1088; https://doi.org/10.3390/biomedicines12051088 - 14 May 2024
Abstract
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15–20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as
[...] Read more.
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15–20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody–drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody® molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
►▼
Show Figures
Figure 1
Open AccessArticle
Cellular Responses Induced by NCT-503 Treatment on Triple-Negative Breast Cancer Cell Lines: A Proteomics Approach
by
Ioana-Ecaterina Pralea, Radu-Cristian Moldovan, Adrian-Bogdan Țigu, Cristian-Silviu Moldovan, Eva Fischer-Fodor and Cristina-Adela Iuga
Biomedicines 2024, 12(5), 1087; https://doi.org/10.3390/biomedicines12051087 - 14 May 2024
Abstract
Breast cancer (BC) remains one of the leading causes of mortality among women, with triple-negative breast cancer (TNBC) standing out for its aggressive nature and limited treatment options. Metabolic reprogramming, one of cancer’s hallmarks, underscores the importance of targeting metabolic vulnerabilities for therapeutic
[...] Read more.
Breast cancer (BC) remains one of the leading causes of mortality among women, with triple-negative breast cancer (TNBC) standing out for its aggressive nature and limited treatment options. Metabolic reprogramming, one of cancer’s hallmarks, underscores the importance of targeting metabolic vulnerabilities for therapeutic intervention. This study aimed to investigate the impact of de novo serine biosynthetic pathway (SSP) inhibition, specifically targeting phosphoglycerate dehydrogenase (PHGDH) with NCT-503, on three TNBC cell lines: MDA-MB-231, MDA-MB-468 and Hs 578T. First, MS-based proteomics was used to confirm the distinct expression of PHGDH and other SSP enzymes using the intracellular proteome profiles of untreated cells. Furthermore, to characterize the response of the TNBC cell lines to the inhibitor, both in vitro assays and label-free, bottom-up proteomics were employed. NCT-503 exhibited significant cytotoxic effects on all three cell lines, with MDA-MB-468 being the most susceptible (IC50 20.2 ± 2.8 µM), while MDA-MB-231 and Hs 578T showed higher, comparable IC50s. Notably, differentially expressed proteins (DEPs) induced by NCT-503 treatment were mostly cell line-specific, both in terms of the intracellular and secreted proteins. Through overrepresentation and Reactome GSEA analysis, modifications of the intracellular proteins associated with cell cycle pathways were observed in the MDA-MBs following treatment. Distinctive dysregulation of signaling pathways were seen in all TNBC cell lines, while modifications of proteins associated with the extracellular matrix organization characterizing both MDA-MB-231 and Hs 578T cell lines were highlighted through the treatment-induced modifications of the secreted proteins. Lastly, an analysis was conducted on the DEPs that exhibited greater abundance in the NCT-503 treatment groups to evaluate the potential chemo-sensitizing properties of NCT-503 and the druggability of these promising targets.
Full article
(This article belongs to the Special Issue Mechanisms of Cell Death in Cancer Cells: A New Therapeutic Opportunity)
►▼
Show Figures
Figure 1
Open AccessArticle
Hotspot DNA Methyltransferase 3A (DNMT3A) and Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy
by
Nadine E. Struckman, Rob C. M. de Jong, M. Willy Honders, Sophie-Anne I. Smith, Dyantha I. van der Lee, Georgia Koutsoumpli, Arnoud H. de Ru, Jan-Henrik Mikesch, Peter A. van Veelen, J. H. Frederik Falkenburg and Marieke Griffioen
Biomedicines 2024, 12(5), 1086; https://doi.org/10.3390/biomedicines12051086 - 14 May 2024
Abstract
DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 and 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7–23% of patients with acute myeloid leukemia. Here, we investigated whether hotspot mutations in these genes encode neoantigens that
[...] Read more.
DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 and 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7–23% of patients with acute myeloid leukemia. Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five human B-lymphoblastoid cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. From these minigene-transduced cell lines, peptides were eluted from HLA class I alleles and analyzed using tandem mass spectrometry. The resulting data are available via ProteomeXchange under the identifier PXD050560. Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens. For these neopeptides, peptide–HLA tetramers were produced to search for specific T-cells in healthy individuals. Various T-cell clones were isolated showing specific reactivity against cell lines transduced with full-length DNMT3AR882H or IDH2R140Q genes, while cell lines transduced with wildtype genes were not recognized. One T-cell clone for DNMT3AR882H also reacted against patient-derived acute myeloid leukemia cells with the mutation, while patient samples without the mutation were not recognized, thereby validating the surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted in acute myeloid leukemia via immunotherapy.
Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
►▼
Show Figures
Graphical abstract
Open AccessReview
Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients
by
Giulia Marrone, Kevin Cornali, Manuela Di Lauro, Maria Josè Ceravolo, Luca Di Marco, Simone Manca di Villahermosa, Anna Paola Mitterhofer and Annalisa Noce
Biomedicines 2024, 12(5), 1085; https://doi.org/10.3390/biomedicines12051085 - 14 May 2024
Abstract
In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of
[...] Read more.
In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium–glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.
Full article
(This article belongs to the Special Issue Pharmaceutical Treatments for Typical CKD Comorbidities)
►▼
Show Figures
Figure 1
Open AccessArticle
Prediction of Initial CRP/Albumin Ratio on In-Hospital Mortality in Isolated Traumatic Brain Injury Patients
by
Michaela Friedrich, Kristin Haferkorn, Marco Stein, Eberhard Uhl and Michael Bender
Biomedicines 2024, 12(5), 1084; https://doi.org/10.3390/biomedicines12051084 - 14 May 2024
Abstract
The CRP/albumin ratio (CAR) is a mortality predictor in intensive care unit (ICU) patients. The aim of the current study was to investigate the ability of CAR to predict in-hospital mortality (IHM) in patients with isolated traumatic brain injury (iTBI). We performed a
[...] Read more.
The CRP/albumin ratio (CAR) is a mortality predictor in intensive care unit (ICU) patients. The aim of the current study was to investigate the ability of CAR to predict in-hospital mortality (IHM) in patients with isolated traumatic brain injury (iTBI). We performed a retrospective analysis including 200 patients with iTBI admitted to our neurosurgical intensive care unit (NICU) between September 2014 and December 2016. Serum biomarkers, demographic and radiological data, several ICU scores, and cardiopulmonary parameters were analyzed. The rate of IHM was 27.5% (55/200) and significantly associated with a higher AIS head score (p < 0.0001), a lower albumin level (p < 0.0001), and the necessity of a higher level of inspiratory oxygen fraction (p = 0.002). Furthermore, advanced age (odds ratio [OR] = 0.953, 95% confidence interval [CI] = 0.927–0.981, p = 0.001), a lower GCS score (OR = 1.347, 95% CI = 1.203–1.509, p < 0.0001), a higher level of lactate (OR = 0.506, 95% CI = 0.353–0.725, p < 0.0001), a higher CAR (OR = 0.547, 95% CI = 0.316–0.945, p = 0.031) and a higher norepinephrine application rate (OR = 0.000, 95% CI 0.000–0.090, p = 0.016) were identified as independent predictors of IHM. ROC analysis showed an association between IHM and a CAR cut-off value of >0.38 (Youden index 0.073, sensitivity: 27.9, specificity: 64.8, p = 0.044). We could identify a CAR > 0.38 as a new independent predictor for IHM in patients with iTBI.
Full article
(This article belongs to the Special Issue Brain Injury: New Insights into Mechanisms and Future Promising Treatments)
►▼
Show Figures
Figure 1
Open AccessEditorial
A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses
by
Masaru Tanaka and László Vécsei
Biomedicines 2024, 12(5), 1083; https://doi.org/10.3390/biomedicines12051083 (registering DOI) - 13 May 2024
Abstract
Welcome to Biomedicines’ 10th Anniversary Special Issue, a journey through the human mind’s labyrinth and complex neurological pathways [...]
Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Translational Laboratory and Experimental Medicine for the Sake of Neurological Diseases and Mental Illnesses)
Open AccessArticle
Selenium and Arsenic Levels, Prevalence of Common Variants of Genes Involved in Their Metabolism, and Psoriasis Disease
by
Tadeusz Dębniak, Piotr Baszuk, Ewa Duchnik, Karolina Rowińska, Emilia Rogoża-Janiszewska, Magdalena Boer, Magdalena Kiedrowicz, Mariola Marchlewicz, Daniel Watola, Martyna Feherpataky, Róża Derkacz, Anna Dębniak, Wojciech Marciniak, Katarzyna Gołębiewska, Jan Lubiński, Rodney J. Scott and Jacek Gronwald
Biomedicines 2024, 12(5), 1082; https://doi.org/10.3390/biomedicines12051082 - 13 May 2024
Abstract
Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped
[...] Read more.
Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped 336 patients and 903 matched controls to evaluate the prevalence of SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) polymorphisms using Taqman assays. The mean selenium (Se) level in serum was 74 µg/L in patients and 86 µg/L in controls (p < 0.001). The mean Se level in blood was 95 µg/L in patients and 111 µg/L in controls (p < 0.001). Psoriasis risk was greatest among participants with the lowest serum (<68.75 µg/L, OR: 8.30; p < 0.001) and lowest blood concentrations of Se (<88.04 µg/L, OR: 10.3; p < 0.001). Similar results were observed in subgroups of males and females. We found an inverse correlation of selenium levels with PASI, NAPSI, and BSA scores. There was no significant difference in the distribution of the CAT, GPX1, DMGDH, and SOD2 polymorphisms. Among carriers of rs4880, rs1001179, and rs921943 polymorphisms, blood selenium levels were significantly lower. The mean arsenic level in serum was 0.79 µg/L in patients and 0.7 µg/L in controls (p = 0.2). The mean concentration in blood was 1.1 µg/L in patients and 1.3 µg/L in controls (p < 0.001). In conclusion, we found that lower selenium levels, in blood and serum, are associated with psoriasis risk and its more severe course. Future prospective studies should focus on the optimalisation of the concentration of this trace element not only for prophylactic guidance but also to support the treatment of this disease.
Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
Open AccessArticle
Dysregulated Coagulation and Fibrinolysis Are Present in Patients Admitted to the Emergency Department with Acute Hypoxemic Respiratory Failure: A Prospective Study
by
Chrysi Keskinidou, Alice Georgia Vassiliou, Elena Papoutsi, Edison Jahaj, Ioanna Dimopoulou, Ilias Siempos and Anastasia Kotanidou
Biomedicines 2024, 12(5), 1081; https://doi.org/10.3390/biomedicines12051081 - 13 May 2024
Abstract
Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting
[...] Read more.
Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.
Full article
(This article belongs to the Special Issue Molecular Researches in Pro-thrombotic Disorders)
Open AccessEditorial
Special Issue: “Neurodegenerative Diseases: Recent Advances and Future Perspectives”
by
Inés López-Cuenca and Rosa De Hoz
Biomedicines 2024, 12(5), 1080; https://doi.org/10.3390/biomedicines12051080 - 13 May 2024
Abstract
Neurodegenerative diseases include a heterogeneous group of conditions that pose a growing challenge to public health and the scientific community [1] [...]
Full article
(This article belongs to the Special Issue Neurodegenerative Diseases: Recent Advances and Future Perspectives)
Open AccessArticle
Benzamide Trimethoprim Derivatives as Human Dihydrofolate Reductase Inhibitors—Molecular Modeling and In Vitro Activity Study
by
Danuta Drozdowska, Agnieszka Wróbel-Tałałaj, Cezary Parzych and Artur Ratkiewicz
Biomedicines 2024, 12(5), 1079; https://doi.org/10.3390/biomedicines12051079 - 13 May 2024
Abstract
Human dihydrofolate reductase (hDHFR) is an essential cellular enzyme, and inhibiting its activity is a promising strategy for cancer therapy. We have chosen the trimethoprim molecule (TMP) as a model compound in our search for a new class of
[...] Read more.
Human dihydrofolate reductase (hDHFR) is an essential cellular enzyme, and inhibiting its activity is a promising strategy for cancer therapy. We have chosen the trimethoprim molecule (TMP) as a model compound in our search for a new class of hDHFR inhibitors. We incorporated an amide bond, a structural element typical of netropsin, a ligand that binds selectively in the minor groove of DNA, into the molecules of TMP analogs. In this work, we present previously obtained and evaluated eleven benzamides (JW1–JW8; MB1, MB3-MB4). Recently, these compounds were specifically projected as potential inhibitors of the enzymes acetylcholinesterase (AChE) and β-secretase (BACE1). JW8 was most active against AChE, with an inhibitory concentration of AChE IC50 = 0.056 µM, while the IC50 for donepezil was 0.046 µM. This compound was also the most active against the BACE1 enzyme. The IC50 value was 9.01 µM compared to that for quercetin, with IC50 = 4.89 µM. All the benzamides were active against hDHFR, with IC50 values ranging from 4.72 to 20.17 µM, and showed activity greater than TMP (55.26 µM). Quantitative results identified the derivatives JW2 and JW8 as the most promising. A molecular modeling study demonstrates that JW2 interacts strongly with the key residue Gly-117, while JW8 interacts strongly with Asn-64 and Arg-70. Furthermore, JW2 and JW8 demonstrate the ability to stabilize the hDHFR enzyme, despite forming fewer hydrogen bonds with the protein compared to reference ligands. It can be concluded that this class of compounds certainly holds great promise for good active leads in medicinal chemistry.
Full article
(This article belongs to the Special Issue State-of-the-Art Drug Discovery and Development in Poland)
Open AccessArticle
Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses
by
Amirmoezz Yonesi, Kei Tomihara, Danki Takatsuka, Hidetake Tachinami, Manabu Yamazaki, Amir Reza Younesi Jadidi, Mayu Takaichi, Shuichi Imaue, Kumiko Fujiwara, Shin-Ichi Yamada, Jun-Ichi Tanuma and Makoto Noguchi
Biomedicines 2024, 12(5), 1078; https://doi.org/10.3390/biomedicines12051078 - 13 May 2024
Abstract
Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses
[...] Read more.
Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses in vitro. We investigated the effect of in vivo administration of rapamycin on immune cell distribution and T cell immune responses in oral tumor-bearing mice. Results: Rapamycin treatment significantly inhibited OSCC cell proliferation and migration, increased apoptotic cell death, and upregulated cell surface expression of several immune accessory and adhesion molecules, including CD40, CD83, PD-L1, PD-L2, MHC class I, P-selectin, and VCAM-1. These cancer cells augmented T cell proliferation. In vivo rapamycin administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T cells, CD8+ T cells, and dendritic cells (DCs); decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor cells and regulatory T cells; enhanced DC maturation and upregulated the surface expression of CD40, CD86, and ICAM-1. Conclusions: Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects.
Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
►▼
Show Figures
Figure 1
Open AccessArticle
Platelets Induce Cell Apoptosis of Cardiac Cells via FasL after Acute Myocardial Infarction
by
Kim J. Krott, Friedrich Reusswig, Matthias Dille, Evelyn Krüger, Simone Gorressen, Saoussen Karray, Amin Polzin, Malte Kelm, Jens W. Fischer and Margitta Elvers
Biomedicines 2024, 12(5), 1077; https://doi.org/10.3390/biomedicines12051077 - 13 May 2024
Abstract
Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion (I/R) injury, leading to cardiac damage and dysfunction. Platelets are major players in hemostasis and play a
[...] Read more.
Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion (I/R) injury, leading to cardiac damage and dysfunction. Platelets are major players in hemostasis and play a crucial role in vessel occlusion, inflammation, and cardiac remodeling after I/R. Here, we studied the impact of platelets on cell apoptosis in the myocardium using a close-chest mouse model of AMI. We found caspase-3-positive resident cardiac cells, while leukocytes were negative for caspase-3. Using two different mouse models of thrombocytopenia, we detected a significant reduction in caspase-3 positive cells in the infarct border zone after I/R injury. Further, we identified platelet FasL to induce cell apoptosis via the extrinsic pathway of Fas receptor activation of target cells. Mechanistically, hypoxia triggers platelet adhesion to FasR, suggesting that platelet-induced apoptosis is elevated after I/R. Platelet-specific FasL knock-out mice showed reduced Bax and Bcl2 expression, suggesting that platelets modulate the intrinsic and extrinsic pathways of apoptosis, leading to reduced infarct size after myocardial I/R injury. Thus, a new mechanism for how platelets contribute to tissue homeostasis after AMI was identified that should be validated in patients soon.
Full article
(This article belongs to the Special Issue Molecular Insights into Myocardial Infarction)
Open AccessReview
Unraveling TAFRO Syndrome: An In-Depth Look at the Pathophysiology, Management, and Future Perspectives
by
Juan Carlos Caballero, Nazaret Conejero, Laura Solan, Francisco Javier Diaz de la Pinta, Raul Cordoba and Alberto Lopez-Garcia
Biomedicines 2024, 12(5), 1076; https://doi.org/10.3390/biomedicines12051076 - 13 May 2024
Abstract
TAFRO syndrome is a rare and aggressive inflammatory entity characterized by thrombocytopenia, anasarca, fever, renal failure, reticulin fibrosis, and organomegaly. This entity supposes a diagnostic and therapeutic challenge due to its significant overlap with Castleman’s disease. However, distinct clinical and histological features warrant
[...] Read more.
TAFRO syndrome is a rare and aggressive inflammatory entity characterized by thrombocytopenia, anasarca, fever, renal failure, reticulin fibrosis, and organomegaly. This entity supposes a diagnostic and therapeutic challenge due to its significant overlap with Castleman’s disease. However, distinct clinical and histological features warrant its classification as a separate subtype of idiopathic multicentric Castleman’s disease (iMCD). While recent modifications have been made to the diagnostic criteria for iMCD, these criteria lack specificity for this particular condition, further complicating diagnosis. Due to its inflammatory nature, several complex molecular signaling pathways are involved, including the JAK-STAT pathway, NF-kB, and signal amplifiers such as IL-6 and VEGF. Understanding the involvement of immune dysfunction, some infectious agents, genetic mutations, and specific molecular and signaling pathways could improve the knowledge and management of the condition, leading to effective treatment strategies. The current therapeutic approaches include corticosteroids, anti-IL6 drugs, rituximab, and chemotherapy, among others, but response rates vary, highlighting the need for personalized strategies. The prognosis is uncertain due to diagnostic difficulties, emphasizing the importance of early intervention and appropriate targeted treatment. This comprehensive review examines the evolving landscape of TAFRO syndrome, including the pathophysiology, diagnostic criteria, treatment strategies, prognosis, and future perspectives.
Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of TAFRO Syndrome)
►▼
Show Figures
Figure 1
Open AccessReview
Intersecting Paths: Unraveling the Complex Journey of Cancer to Bone Metastasis
by
Nour Arakil, Shahid Akhtar Akhund, Basant Elaasser and Khalid S. Mohammad
Biomedicines 2024, 12(5), 1075; https://doi.org/10.3390/biomedicines12051075 - 13 May 2024
Abstract
The phenomenon of bone metastases presents a significant challenge within the context of advanced cancer treatments, particularly pertaining to breast, prostate, and lung cancers. These metastatic occurrences stem from the dissemination of cancerous cells into the bone, thereby interrupting the equilibrium between osteoblasts
[...] Read more.
The phenomenon of bone metastases presents a significant challenge within the context of advanced cancer treatments, particularly pertaining to breast, prostate, and lung cancers. These metastatic occurrences stem from the dissemination of cancerous cells into the bone, thereby interrupting the equilibrium between osteoblasts and osteoclasts. Such disruption results in skeletal complications, adversely affecting patient morbidity and quality of life. This review discusses the intricate interplay between cancer cells and the bone microenvironment, positing the bone not merely as a passive recipient of metastatic cells but as an active contributor to cancer progression through its distinctive biochemical and cellular makeup. A thorough examination of bone structure and the dynamics of bone remodeling is undertaken, elucidating how metastatic cancer cells exploit these processes. This review explores the genetic and molecular pathways that underpin the onset and development of bone metastases. Particular emphasis is placed on the roles of cytokines and growth factors in facilitating osteoclastogenesis and influencing osteoblast activity. Additionally, this paper offers a meticulous critique of current diagnostic methodologies, ranging from conventional radiography to advanced molecular imaging techniques, and discusses the implications of a nuanced understanding of bone metastasis biology for therapeutic intervention. This includes the development of targeted therapies and strategies for managing bone pain and other skeletal-related events. Moreover, this review underscores the imperative of ongoing research efforts aimed at identifying novel therapeutic targets and refining management approaches for bone metastases. It advocates for a multidisciplinary strategy that integrates advancements in medical oncology and radiology with insights derived from molecular biology and genetics, to enhance prognostic outcomes and the quality of life for patients afflicted by this debilitating condition. In summary, bone metastases constitute a complex issue that demands a comprehensive and informed approach to treatment. This article contributes to the ongoing discourse by consolidating existing knowledge and identifying avenues for future investigation, with the overarching objective of ameliorating patient care in the domain of oncology.
Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))
►▼
Show Figures
Figure 1
Open AccessReview
Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson’s Disease and Aging
by
Amy Gathings, Vandana Zaman, Narendra L. Banik and Azizul Haque
Biomedicines 2024, 12(5), 1074; https://doi.org/10.3390/biomedicines12051074 - 13 May 2024
Abstract
Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho,
[...] Read more.
Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, plays a significant role in the cellular pathology of PD. The downstream effector of Rho, Rho-associated kinase (ROCK), plays multiple functions, including microglial activation and induction of inflammatory responses. Activated microglia have been implicated in the pathology of many neurodegenerative diseases, including PD, that initiate inflammatory responses, leading to neuron death. Calpain expression and activity is increased following glial activation, which triggers the Rho-ROCK pathway and induces inflammatory T cell activation and migration as well as mediates toxic α-synuclein (α-syn) aggregation and neuron death, indicating a pivotal role for calpain in the inflammatory and degenerative processes in PD. Increased calpain activity and Rho-ROCK activation may represent a new mechanism for increased oxidative damage in aging. This review will summarize calpain activation and the role of the Rho-ROCK pathway in oxidative stress and α-syn aggregation, their influence on the neurodegenerative process in PD and aging, and possible strategies and research directions for therapeutic intervention.
Full article
(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)
►▼
Show Figures
Figure 1
Open AccessArticle
Ubiquitin-Specific Protease 18 in Chronic Kidney Disease—Another Emerging Biomarker to Consider?
by
Paulina Dziamałek-Macioszczyk, Agata Winiarska, Anna Pawłowska, Jan Macioszczyk, Paweł Wojtacha and Tomasz Stompór
Biomedicines 2024, 12(5), 1073; https://doi.org/10.3390/biomedicines12051073 - 13 May 2024
Abstract
Ubiquitin-specific protease 18 (USP18) is a protein recognized for its dual enzymatic and non-enzymatic nature. It is involved in many physiological processes like the cell cycle and cell signaling. It also suppresses heart muscle remodeling upon an increase in the afterload. The role
[...] Read more.
Ubiquitin-specific protease 18 (USP18) is a protein recognized for its dual enzymatic and non-enzymatic nature. It is involved in many physiological processes like the cell cycle and cell signaling. It also suppresses heart muscle remodeling upon an increase in the afterload. The role of USP18 in kidney pathology remains unknown. The objective of the study was to assess the relationship between serum and urine USP18 levels, the factors contributing to cardiovascular risk, and the markers of kidney disease activity at different stages of chronic kidney disease (CKD). One hundred participants, aged between 24 and 85 years (mean 53.1 ± 17.1 years), were included. Five groups (n = 20 each) were recruited according to their renal status (healthy individuals, patients with proteinuric glomerulonephritis, patients with non-proteinuric CKD, patients who were treated with hemodialysis, and kidney transplant recipients). The measurements of serum and urine USP18 levels were performed using ELISA. The median serum USP18 level was the highest in healthy participants (1143.0 pg/mL) and kidney transplant recipients (856.6 pg/mL), whereas, in individuals with different forms of CKD, it fitted within the range of 402.1–471.9 pg/mL. Urinary USP18 reached the highest level in the group of CKD patients not yet on dialysis (303.3 pg/mL). Only in this group did it correlate with serum creatinine and urea concentrations. Our results suggest the inhibition of cardioprotective USP18 signaling when kidney function is impaired. Moreover, an increased level of urinary USP18 may indicate chronic tubular damage.
Full article
(This article belongs to the Special Issue Research Advances in Kidney Diseases and Sepsis)
►▼
Show Figures
Figure 1
Open AccessArticle
The Pathway-Selective Dependence of Nitric Oxide for Long-Term Potentiation in the Anterior Cingulate Cortex of Adult Mice
by
Qi-Yu Chen, Jinjin Wan, Yujie Ma and Min Zhuo
Biomedicines 2024, 12(5), 1072; https://doi.org/10.3390/biomedicines12051072 - 12 May 2024
Abstract
Nitric oxide (NO) is a key diffusible messenger in the mammalian brain. It has been proposed that NO may diffuse in retrograde into presynaptic terminals, contributing to the induction of hippocampal long-term potentiation (LTP). Here, we present novel evidence that NO is selectively
[...] Read more.
Nitric oxide (NO) is a key diffusible messenger in the mammalian brain. It has been proposed that NO may diffuse in retrograde into presynaptic terminals, contributing to the induction of hippocampal long-term potentiation (LTP). Here, we present novel evidence that NO is selectively required for the synaptic potentiation of the interhemispheric projection in the anterior cingulate cortex (ACC). Unilateral low-frequency stimulation (LFS) induced a short-term synaptic potentiation on the contralateral ACC through the corpus callosum (CC). The use of the antagonists of the NMDA receptor (NMDAR), or the inhibitor of the L-type voltage-dependent Ca2+ channels (L-VDCCs), blocked the induction of this ACC-ACC potentiation. In addition, the inhibitor of NO synthase, or inhibitors for its downstream signaling pathway, also blocked this ACC-ACC potentiation. However, the application of the NOS inhibitor blocked neither the local electric stimulation-induced LTP nor the stimulation-induced recruitment of silent responses. Our results present strong evidence for the pathway-selective roles of NO in the LTP of the ACC.
Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- Biomedicines Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomedicines, Cancers, JFB, Nanomaterials, Polymers
Advanced Functional Materials for Regenerative Medicine
Topic Editors: Antonino Morabito, Luca ValentiniDeadline: 6 June 2024
Topic in
Biomedicines, Current Oncology, Diagnostics, Gastrointestinal Disorders, JCM
Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice
Topic Editors: Davide Giuseppe Ribaldone, Gian Paolo CavigliaDeadline: 20 June 2024
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Topic in
Cancers, Diagnostics, JCM, Current Oncology, Gastrointestinal Disorders, Biomedicines
Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments
Topic Editors: Alessandro Coppola, Damiano Caputo, Roberta Angelico, Domenech Asbun, Chiara MazzarelliDeadline: 20 July 2024
Conferences
Special Issues
Special Issue in
Biomedicines
The IGF2-Regulated Cellular- and Genetic Network in Physiology and Disease: A Call to Action
Guest Editor: Pierluigi ScaliaDeadline: 15 May 2024
Special Issue in
Biomedicines
Advances in Therapeutic Strategies in Gynecological Malignant Tumors
Guest Editor: Alberto FarolfiDeadline: 31 May 2024
Special Issue in
Biomedicines
Drugs Targeting the Disease Progression, Cognitive Impairment, Anxiety and Other Co-morbidities in Epilepsy: From Bench to Bedside
Guest Editors: Diana Cunha-Reis, Paulo Correia-de-SáDeadline: 15 June 2024
Special Issue in
Biomedicines
Advanced Research in Tissue Engineering and Cellular Culture and Their Applications
Guest Editors: Victor Palarie, Peer Wolfgang KämmererDeadline: 30 June 2024
Topical Collections
Topical Collection in
Biomedicines
OMICs and Complex Diseases
Collection Editors: Mostafa Dianatinasab, Anke Wesselius, Amin Salehi-Abargouei
Topical Collection in
Biomedicines
Feature Papers in Cancer Biology and Therapeutics
Collection Editor: Veronique Baud
Topical Collection in
Biomedicines
Feature Papers in Gene and Cell Therapy
Collection Editor: Bernard Lebleu
Topical Collection in
Biomedicines
Feature Papers in Microbiology in Human Health and Disease
Collection Editor: Ryota Niikura