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
The Pathway-Selective Dependence of Nitric Oxide for Long-Term Potentiation in the Anterior Cingulate Cortex of Adult Mice
Biomedicines 2024, 12(5), 1072; https://doi.org/10.3390/biomedicines12051072 (registering DOI) - 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
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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.
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(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review
by
Xinghui Liu, Miao Yang, Gregory Y. H. Lip and Garry McDowell
Biomedicines 2024, 12(5), 1071; https://doi.org/10.3390/biomedicines12051071 (registering DOI) - 12 May 2024
Abstract
Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system.
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Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.
Full article
(This article belongs to the Special Issue Genetics, Obesity, Diabetes and Metabolic Syndrome)
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Open AccessCase Report
Tacrolimus Treatment for TAFRO Syndrome
by
Taiichiro Shirai, Shinya Ichikawa and Jun Saegusa
Biomedicines 2024, 12(5), 1070; https://doi.org/10.3390/biomedicines12051070 (registering DOI) - 12 May 2024
Abstract
TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those
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TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus.
Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of TAFRO Syndrome)
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Open AccessArticle
The Effect of Denosumab on Rotator Cuff Repair in Women Aged 60 and over with Osteoporosis: A Prospective Observational Study
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Ki-Tae Kim, Sanghyeon Lee, Ho-Won Lee, Shi-Hyun Kim and Yong-Beom Lee
Biomedicines 2024, 12(5), 1069; https://doi.org/10.3390/biomedicines12051069 (registering DOI) - 12 May 2024
Abstract
Background: In previous studies, denosumab, a RANKL human monoclonal antibody used in osteoporosis treatment, has shown efficacy in tendon healing after rotator cuff repair. This prospective study investigated the effects of denosumab on tendon healing, re-tear rates, and clinical outcomes post rotator cuff
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Background: In previous studies, denosumab, a RANKL human monoclonal antibody used in osteoporosis treatment, has shown efficacy in tendon healing after rotator cuff repair. This prospective study investigated the effects of denosumab on tendon healing, re-tear rates, and clinical outcomes post rotator cuff repair in women with osteoporosis. Method: This was a prospective, observational study, employing propensity score matching for the control group. From March 2018 to March 2023, female patients over the age of 60 with normal bone density undergoing arthroscopic rotator cuff repair were selected as controls through propensity score matching (PSM) and compared with female patients of the same age group with osteoporosis who were receiving denosumab treatment. The control group was matched using 1-to-2 propensity score matching. Radiological examinations and functional outcomes were assessed preoperatively and at 6 months postoperatively. Results: In the final analysis, the study comprised 34 patients in the denosumab treatment group (Group 1) and 68 patients in the control group (Group 2). The functional scores showed significant improvement at 6 months post-surgery in both groups. No significant difference in the functional scores was observed among the groups. The re-tear rate, defined according to Sugaya’s classification (types IV and V) as re-tear, was slightly higher in Group 1 at 16.7% (6 of 34) compared to Group 2 at 11.7% (8 of 68), but the difference was not statistically significant (p = 0.469). The re-tear patterns, classified according to Rhee’s classification, also showed no significant difference among the groups (Group 1: 2/4 of 6; Group 2: 4/4 of 8; p = 0.571). The occurrence of type I re-tear exhibited no significant difference between the two groups (5.9% vs. 5.9%; p = 1.000). Conclusions: The administration of denosumab following arthroscopic rotator cuff repair in women aged 60 and over with osteoporosis resulted in a re-tear rate that was similar to that observed in patients without osteoporosis. This result suggests that denosumab administration might be beneficial for rotator cuff healing, particularly in the context of osteoporosis, a known risk factor for increased retear rates. Therefore, comprehensive osteoporosis screening and treatment should be considered in conjunction with rotator cuff repair surgery in middle-aged women.
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(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)
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Open AccessArticle
Prevalence of Dysmagnesemia among Patients with Diabetes Mellitus and the Associated Health Outcomes: A Cross-Sectional Study
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Salwa Al Harasi, Juhaina Salim Al-Maqbali, Henrik Falhammar, Ali Al-Mamari, Abdullah Al Futisi, Ahmed Al-Farqani, Suneel Kumar, Alaa Osman, Sulaiman Al Riyami, Nafila Al Riyami, Qatiba Al Farai, Hiba Al Alawi and Abdullah M. Al Alawi
Biomedicines 2024, 12(5), 1068; https://doi.org/10.3390/biomedicines12051068 (registering DOI) - 12 May 2024
Abstract
Introduction: Magnesium is a vital intracellular cation crucial for over 320 enzymatic reactions related to energy metabolism, musculoskeletal function, and nucleic acid synthesis and plays a pivotal role in human physiology. This study aimed to explore the prevalence of dysmagnesemia in patients with
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Introduction: Magnesium is a vital intracellular cation crucial for over 320 enzymatic reactions related to energy metabolism, musculoskeletal function, and nucleic acid synthesis and plays a pivotal role in human physiology. This study aimed to explore the prevalence of dysmagnesemia in patients with diabetes mellitus and evaluate its correlations with glycemic control, medication use, and diabetic complications. Methods: A cross-sectional study was conducted at Sultan Qaboos University Hospital, including 316 patients aged 18 years or older with diabetes mellitus. Data included demographics, medical history, medications, and biochemical parameters. Serum total magnesium concentrations were measured, and dysmagnesemia was defined as magnesium ≤ 0.69 mmol/L for hypomagnesemia and ≥1.01 mmol/L for hypermagnesemia. Results: The prevalence of hypomagnesemia in patients with diabetes was 17.1% (95% CI: 13.3–21.7%), and hypermagnesemia was 4.1% (95% CI: 2.4–7.0%). Females were significantly overrepresented in the hypomagnesemia group, while the hypermagnesemia group showed a higher prevalence of hypertension, retinopathy, an increased albumin/creatinine ratio, chronic kidney disease (CKD), elevated creatinine levels, and a lower adjusted calcium concentration. The multinominal logistic regression exhibited that the female sex and higher serum-adjusted calcium were independent risk factors of hypomagnesemia. In contrast, the presence of hypertension, higher levels of albumin/creatinine ratio, and stage 5 CKD were independent risk factors of hypermagnesemia. Conclusions: Hypomagnesemia was common among patients with diabetes mellitus; however, hypermagnesemia was associated with microvascular complications.
Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
Open AccessArticle
Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients
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João Meira Gonçalves, Bruno Carvalho, Rui Tuna, Patricia Polónia and Paulo Linhares
Biomedicines 2024, 12(5), 1067; https://doi.org/10.3390/biomedicines12051067 (registering DOI) - 12 May 2024
Abstract
In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width—Coefficient of Variation)—in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment
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In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width—Coefficient of Variation)—in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with the overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan–Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in the NLR, PLR, and RDW-CV across different treatment stages. The NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p = 0.007, η2p = 0.06; PLR: p = 0.001, η2p = 0.23), while the RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p = 0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, a higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR = 1.03, p = 0.029; RDW-CV at progression: HR = 1.14, p = 0.004). We proposed specific marker cut-offs that demonstrated significant associations with survival outcomes when applied to Kaplan–Meier survival curves (NLR at 2nd line < 5: p < 0.017; RDW-CV at progression < 15: p = 0.007). An elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.
Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma)
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Open AccessArticle
Analysis of the Associations of Measurements of Body Composition and Inflammatory Factors with Cardiovascular Disease and Its Comorbidities in a Community-Based Study
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Nader Tarabeih, Alexander Kalinkovich, Shai Ashkenazi, Stacey S. Cherny, Adel Shalata and Gregory Livshits
Biomedicines 2024, 12(5), 1066; https://doi.org/10.3390/biomedicines12051066 (registering DOI) - 11 May 2024
Abstract
The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)],
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The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)], body composition, levels of soluble markers, and other measures were collected from 1079 individuals. When we examined the association of each comorbidity and CVD, controlling for other comorbidities, we observed a clear pattern of the comorbidity-related specific associations with tested covariates. For example, T2DM was significantly associated with GDF-15 levels and the leptin/adiponectin (L/A) ratio independently of two other comorbidities; HTN, similarly, was independently associated with extracellular water (ECW) levels, L/A ratio, and age; and HDL was independently related to age only. CVD showed very strong independent associations with each of the comorbidities, being associated most strongly with HTN (OR = 10.89, 6.46–18.38) but also with HDL (2.49, 1.43–4.33) and T2DM (1.93, 1.12–3.33). An additive Bayesian network analysis suggests that all three comorbidities, particularly HTN, GDF-15 levels, and ECW content, likely have a main role in the risk of CVD development. Other factors, L/A ratio, lymphocyte count, and the systemic inflammation response index, are likely indirectly related to CVD, acting through the comorbidities and ECW.
Full article
(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)
Open AccessBrief Report
Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer
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Aseem Rai Bhatnagar, Farzan Siddiqui, Gazala Khan, Robert Pompa, David Kwon and Shyam Nyati
Biomedicines 2024, 12(5), 1065; https://doi.org/10.3390/biomedicines12051065 (registering DOI) - 11 May 2024
Abstract
The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The
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The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.
Full article
(This article belongs to the Special Issue Virotherapy and Gene Therapy in Cancer)
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Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model
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Maria Siemionow, Lucile Chambily and Sonia Brodowska
Biomedicines 2024, 12(5), 1064; https://doi.org/10.3390/biomedicines12051064 (registering DOI) - 11 May 2024
Abstract
Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo
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Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo study, we assessed HUDC safety and biodistribution in the NOD SCID mouse model at 90 days following the systemic intraosseous administration of HUDCs. Twelve NOD SCID mice (n = 6/group) received intraosseous injection of donor UCB cells (3.0 × 106) in Group 1, or HUDCs (3.0 × 106) in Group 2, without immunosuppression. Flow cytometry assessed hematopoietic cell surface markers in peripheral blood and the presence of HLA-ABC class I antigens in lymphoid and non-lymphoid organs. HUDC safety was assessed by weekly evaluations, magnetic resonance imaging (MRI), and at autopsy for tumorigenicity. At 90 days after intraosseous cell administration, the comparable expression of HLA-ABC class I antigens in selected organs was found in UCB control and HUDC therapy groups. MRI and autopsy confirmed safety by no signs of tumor growth. This study confirmed HUDC biodistribution to selected lymphoid organs following intraosseous administration, without immunosuppression. These data introduce HUDCs as a novel promising approach for immunomodulation in transplantation.
Full article
(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment)
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Open AccessArticle
Cartilage Collagen Neoepitope C2C Expression in the Articular Cartilage and Its Relation to Joint Tissue Damage in Patients with Knee Osteoarthritis
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Taavi Torga, Siim Suutre, Kalle Kisand, Marina Aunapuu and Andres Arend
Biomedicines 2024, 12(5), 1063; https://doi.org/10.3390/biomedicines12051063 (registering DOI) - 11 May 2024
Abstract
Pathological cleavage of type II collagen (Col2) and generation of Col2 neoepitopes can serve as useful molecular markers of the progression of osteoarthritis (OA). One of such potential biomarkers is type II collagen neoepitope C2C. The aim of this study was to correlate
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Pathological cleavage of type II collagen (Col2) and generation of Col2 neoepitopes can serve as useful molecular markers of the progression of osteoarthritis (OA). One of such potential biomarkers is type II collagen neoepitope C2C. The aim of this study was to correlate the degree of articular cartilage damage in OA patients with C2C expression in histological samples of tissues removed during total knee replacement. Cartilage samples were obtained from 27 patients ranging in age from 55 to 66 years. In each patient, medial and lateral tibia plateau samples were analyzed according to the OARSI histopathology grading system. The C2C expression was evaluated on histological slides by semi-quantitative analysis using ImageJ Fiji 2.14.0 software. Spearman’s rank correlation analysis revealed a positive weak correlation (rho = 0.289, p = 0.0356) between the histological grade of tissue damage and the percentage of C2C staining. In addition, a highly significant positive correlation (rho = 0.388, p = 0.0041) was discovered between the osteoarthritis score (combining the histological grade of damage with the OA macroscopic stage) and the percentage of C2C staining in the samples. The C2C expression was detected in all the regions of the articular cartilage (i.e., the superficial zone, mid zone, deep zone and tidemark area, and the zone of calcified cartilage). Our findings imply that local expression of C2C correlates with the articular cartilage damage in OA-affected knees. This confirms that C2C can be used as a prospective marker for assessing pathological changes in the OA course and OA clinical trials.
Full article
(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)
Open AccessEditorial
Unraveling the Complexity of Asthma: Insights from Omics Approaches
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Esther Herrera-Luis and Natalia Hernandez-Pacheco
Biomedicines 2024, 12(5), 1062; https://doi.org/10.3390/biomedicines12051062 (registering DOI) - 11 May 2024
Abstract
Asthma is a heterogeneous respiratory disease that represents a substantial social and economic burden [...]
Full article
(This article belongs to the Special Issue Recent Advances in Asthma Research in a Multiomics Era)
Open AccessArticle
Adipose Tissue Segmentation after Lung Slice Localization in Chest CT Images Based on ConvBiGRU and Multi-Module UNet
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Pengyu Lei, Jie Li, Jizheng Yi and Wenjie Chen
Biomedicines 2024, 12(5), 1061; https://doi.org/10.3390/biomedicines12051061 (registering DOI) - 10 May 2024
Abstract
The distribution of adipose tissue in the lungs is intricately linked to a variety of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Accurate detection and quantitative analysis of subcutaneous and visceral adipose tissue surrounding the lungs are essential
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The distribution of adipose tissue in the lungs is intricately linked to a variety of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Accurate detection and quantitative analysis of subcutaneous and visceral adipose tissue surrounding the lungs are essential for effectively diagnosing and managing these diseases. However, there remains a noticeable scarcity of studies focusing on adipose tissue within the lungs on a global scale. Thus, this paper introduces a ConvBiGRU model for localizing lung slices and a multi-module UNet-based model for segmenting subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), contributing to the analysis of lung adipose tissue and the auxiliary diagnosis of lung diseases. In this study, we propose a bidirectional gated recurrent unit (BiGRU) structure for precise lung slice localization and a modified multi-module UNet model for accurate SAT and VAT segmentations, incorporating an additive weight penalty term for model refinement. For segmentation, we integrate attention, competition, and multi-resolution mechanisms within the UNet architecture to optimize performance and conduct a comparative analysis of its impact on SAT and VAT. The proposed model achieves satisfactory results across multiple performance metrics, including the Dice Score (92.0% for SAT and 82.7% for VAT), F1 Score (82.2% for SAT and 78.8% for VAT), Precision (96.7% for SAT and 78.9% for VAT), and Recall (75.8% for SAT and 79.1% for VAT). Overall, the proposed localization and segmentation framework exhibits high accuracy and reliability, validating its potential application in computer-aided diagnosis (CAD) for medical tasks in this domain.
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(This article belongs to the Section Biomedical Engineering and Materials)
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Open AccessCase Report
Novel ATP2A2 Gene Mutation c.118G>A Causing Keratinocyte and Cardiomyocyte Disconnection in Darier Disease
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Andrea Frustaci, Alessandro De Luca, Romina Verardo, Valentina Guida, Maria Alfarano, Camilla Calvieri, Luigi Sansone, Matteo Antonio Russo and Cristina Chimenti
Biomedicines 2024, 12(5), 1060; https://doi.org/10.3390/biomedicines12051060 (registering DOI) - 10 May 2024
Abstract
Darier disease (DD) is an autosomal dominant disorder due to pathogenic variants of the ATP2A2 gene that causes an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far, although a high incidence of
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Darier disease (DD) is an autosomal dominant disorder due to pathogenic variants of the ATP2A2 gene that causes an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far, although a high incidence of neuropsychiatric syndromes suggests an involvement of the central nervous system. We report that the pathogenic ATP2A2 gene variant c.118G>A may cause cardiac involvement in patients with DD, consisting of keratinocyte and cardiomyocyte disconnection. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsies because cardiac dilatation and dysfunction appeared several decades after skin manifestations. Keratinocyte disconnection was paralleled by cardiomyocyte separation at the lateral junction. Cardiomyocyte separation was associated with cell disarray, sarcoplasmic reticulum dilatation, and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules are associated with chest pain, severe muscle exhaustion, and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation. Cardiac pathologic changes are similar to those documented in the skin, including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors that enhance SERCA2 protein phosphorylation may substantially attenuate the symptoms.
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(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessReview
Structure–Activity Relationships and Therapeutic Applications of Retinoids in View of Potential Benefits from Drug Repurposing Process
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Piotr Kawczak, Igor Feszak, Piotr Brzeziński and Tomasz Bączek
Biomedicines 2024, 12(5), 1059; https://doi.org/10.3390/biomedicines12051059 (registering DOI) - 10 May 2024
Abstract
Vitamin A, an essential micronutrient, is integral to various biological processes crucial for organismal development and maintenance. Dietary sources of vitamin A encompass preformed retinol, retinyl esters, and provitamin A carotenoids. Retinoic acid (RA), a key component, plays pivotal roles in vision, cell
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Vitamin A, an essential micronutrient, is integral to various biological processes crucial for organismal development and maintenance. Dietary sources of vitamin A encompass preformed retinol, retinyl esters, and provitamin A carotenoids. Retinoic acid (RA), a key component, plays pivotal roles in vision, cell proliferation, apoptosis, immune function, and gene regulation. Drug repurposing, an effective strategy for identifying new therapeutic applications for existing drugs, has gained prominence in recent years. This review seeks to provide a comprehensive overview of the current research landscape surrounding retinoids and drug repurposing. The scope of this review encompasses a comprehensive examination of retinoids and their potential for repurposing in various therapeutic contexts. Despite their efficacy in treating dermatological conditions, concerns about toxicity persist, driving the search for safer and more potent retinoids. The molecular mechanisms underlying retinoid activity involve binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs), leading to transcriptional regulation of target genes. This review seeks to shed light on the possibilities for repurposing retinoids to cover a wider spectrum of therapeutic uses by exploring recent scientific progress. It also aims to offer a more comprehensive understanding of the therapeutic prospects of retinoids and the broader impact of drug repositioning in contemporary medicine.
Full article
(This article belongs to the Special Issue Medicinal Chemistry in Drug Design and Discovery)
Open AccessArticle
Botulism Cases in Romania—An Overview of 14-Year National Surveillance Data
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Andreea Marilena Păuna, Maria-Dorina Crăciun, Anca Sîrbu, Rodica Popescu, Bianca Georgiana Enciu, Carmen-Daniela Chivu, Mădălina Simoiu and Daniela Piţigoi
Biomedicines 2024, 12(5), 1058; https://doi.org/10.3390/biomedicines12051058 - 10 May 2024
Abstract
Botulism is a priority disease worldwide because it has a very severe course of evolution that can lead to death. This paper aims to describe the main epidemiological characteristics of botulism cases confirmed in Romania over 14 years (2007–2020). We performed a retrospective
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Botulism is a priority disease worldwide because it has a very severe course of evolution that can lead to death. This paper aims to describe the main epidemiological characteristics of botulism cases confirmed in Romania over 14 years (2007–2020). We performed a retrospective study using the publicly available national surveillance data and reported to the National Institute of Public Health. A total of 325 cases of foodborne botulism were reported in Romania, with no infant or wound botulism. Most of the cases (125, 38.5%) were reported among young adults (25–44 years old), over half (205, 63%) of them living in rural areas. The incriminated food item was identified in 161 cases; in most cases (145, 90%) the food item was prepared in the household. The main food category was represented by meat and meat-based products (94, 68.6%). In almost all cases the identified type was BoNT/B (230/231, 99.5%). Fifteen deaths were recorded, and the case fatality rate was 4.6%. Botulism cases were reported annually in Romania. Surveillance data are essential for implementing control measures and adapting educational campaigns according to existing needs.
Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis, and Therapeutics of Infectious Diseases)
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Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers
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Kyle J. Burghardt, Paul R. Burghardt, Bradley H. Howlett, Sabrina E. Dass, Brent Zahn, Ahmad A. Imam, Abdullah Mallisho, Zaher Msallaty, Berhane Seyoum and Zhengping Yi
Biomedicines 2024, 12(5), 1057; https://doi.org/10.3390/biomedicines12051057 - 10 May 2024
Abstract
Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may
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Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.
Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
Open AccessArticle
Influence of Biofilm Maturity on the Antibacterial Efficacy of Cold Atmospheric Plasma in Oral Microcosm Biofilms
by
Hee-Eun Kim
Biomedicines 2024, 12(5), 1056; https://doi.org/10.3390/biomedicines12051056 - 10 May 2024
Abstract
As biofilms mature, biomass and extracellular polysaccharide (EPS) content increases, enhancing pathogenicity. Therefore, this study aimed to evaluate the antibacterial efficacy of cold atmospheric plasma (CAP) against oral microcosm biofilms and the influence of biofilm maturity on treatment. Oral microcosm biofilms were cultured
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As biofilms mature, biomass and extracellular polysaccharide (EPS) content increases, enhancing pathogenicity. Therefore, this study aimed to evaluate the antibacterial efficacy of cold atmospheric plasma (CAP) against oral microcosm biofilms and the influence of biofilm maturity on treatment. Oral microcosm biofilms were cultured on hydroxyapatite disks for 2 and 6 days. Based on the treatment and biofilm maturity, these were subsequently allocated into six groups (N = 19 each): Groups 1 and 2 were incubated with distilled water for 1 min; Groups 3 and 4 were treated with CAP for 2 min, and Groups 5 and 6 were treated with 0.12% chlorhexidine gluconate for 1 min. Groups 1, 3, and 5 represent 2-day biofilms, and Groups 2, 4, and 6 represent 6-day biofilms. Treatments were repeated daily for 5 days. Antibacterial efficacy was analyzed by measuring oral biofilms’ red fluorescence intensity (RatioR/G) and quantifying EPS content and bacterial viability. The RatioR/G was 1.089-fold and 1.104-fold higher in Groups 4 and 6 than in Groups 3 and 5 following antibacterial treatment, respectively (p < 0.001). EPS content increased by 1.71-fold in Group 6 than in Group 5 (p < 0.001). Bacterial survival rate was the lowest in Group 3 (p = 0.005). These findings underscore the relevance of CAP treatment in maintaining antibacterial efficacy regardless of the biofilm development stage, highlighting its potential utility in oral care.
Full article
(This article belongs to the Special Issue Emerging Trends in Dental Caries: Insights into Etiology, Risk Factors, and Treatment Strategies)
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Open AccessReview
Vascular Endothelial Growth Factor (VEGF) and Its Role in the Cardiovascular System
by
Kamila Florek, Dominik Mendyka and Krzysztof Gomułka
Biomedicines 2024, 12(5), 1055; https://doi.org/10.3390/biomedicines12051055 - 10 May 2024
Abstract
Cardiovascular diseases remain the leading cause of death worldwide, with ischemic heart disease (IHD) as the most common. Ischemia-induced angiogenesis is a process in which vascular endothelial growth factor (VEGF) plays a crucial role. To conduct research in the field of VEGF’s association
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Cardiovascular diseases remain the leading cause of death worldwide, with ischemic heart disease (IHD) as the most common. Ischemia-induced angiogenesis is a process in which vascular endothelial growth factor (VEGF) plays a crucial role. To conduct research in the field of VEGF’s association in cardiovascular diseases, it is vital to understand its role in the physiological and pathological processes in the heart. VEGF-based therapies have demonstrated a promising role in preclinical studies. However, their potential in human therapies is currently under discussion. Furthermore, VEGF is considered a potential biomarker for collateral circulation assessment and heart failure (HF) mortality. Additionally, as VEGF is involved in angiogenesis, there is a need to elucidate the impact of VEGF-targeted therapies in terms of cardiovascular side effects.
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(This article belongs to the Special Issue Angiogenesis)
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Open AccessReview
Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression
by
Serena Travaglini, Massimiliano Marinoni, Valeria Visconte and Luca Guarnera
Biomedicines 2024, 12(5), 1054; https://doi.org/10.3390/biomedicines12051054 - 10 May 2024
Abstract
Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature
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Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature and the subsets of these conditions have changed frequently over time, and despite the fact that, in the last classification, they lost their autonomous entity status and became disease qualifiers, the recognition of this feature remains of major importance. Furthermore, in recent years, extensive studies focusing on clonal hematopoiesis and germline variants shed light on the mechanisms of positive pressure underpinning the rise of driver gene mutations in t-MN. In this manuscript, we aim to review the evolution of defining criteria and characteristics of t-MN from a clinical and biological perspective, the advances in mechanistic aspects of malignant progression and the challenges in prevention and management.
Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
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Open AccessArticle
Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements
by
Stefanos N. Sampatakakis, Niki Mourtzi, Sokratis Charisis, Faidra Kalligerou, Eirini Mamalaki, Eva Ntanasi, Alex Hatzimanolis, Georgios Koutsis, Alfredo Ramirez, Jean-Charles Lambert, Mary Yannakoulia, Mary H. Kosmidis, Efthimios Dardiotis, Georgios Hadjigeorgiou, Paraskevi Sakka, Konstantinos Rouskas, Kostas Patas and Nikolaos Scarmeas
Biomedicines 2024, 12(5), 1053; https://doi.org/10.3390/biomedicines12051053 - 10 May 2024
Abstract
The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer’s Disease (AD), amyloid-beta 42 (Aβ42) and Tau with the odds of SCD using data from
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The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer’s Disease (AD), amyloid-beta 42 (Aβ42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aβ42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aβ42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aβ42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aβ42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.
Full article
(This article belongs to the Special Issue Alzheimer's Disease Genetics)
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