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
Comparison of Intact Fish Skin Graft and Allograft as Temporary Coverage for Full-Thickness Burns: A Non-Inferiority Study
Biomedicines 2024, 12(3), 680; https://doi.org/10.3390/biomedicines12030680 (registering DOI) - 18 Mar 2024
Abstract
The extent and depth of burn injury may mandate temporary use of cadaver skin (allograft) to protect the wound and allow the formation of granulation tissue while split-thickness skin grafts (STSGs) are serially harvested from the same donor areas. However, allografts are not
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The extent and depth of burn injury may mandate temporary use of cadaver skin (allograft) to protect the wound and allow the formation of granulation tissue while split-thickness skin grafts (STSGs) are serially harvested from the same donor areas. However, allografts are not always available and have a high cost, hence the interest in identifying more economical, readily available products that serve the same function. This study evaluated intact fish skin graft (IFSG) as a temporary cover to prepare the wound bed for STSG application. Thirty-six full-thickness (FT) 5 × 5 cm burn wounds were created on the dorsum of six anesthetized Yorkshire pigs on day −1. To mimic the two-stage clinical situation, on day 0, wounds were excised down to a bleeding wound bed and a temporary cover (either IFSG or cadaver porcine skin) was applied; then, on day 7, wounds were debrided to a viable wound bed prior to the application of autologous 1.5:1 meshed STSG (mSTSG). Rechecks were performed on days 14, 21, 28, 45, and 60 with digital images, non-invasive measurements, and punch biopsies. The IFSG created a granulated wound bed receptive to the application of an mSTSG. FT burn wounds treated with an IFSG had similar outcome measures, including contraction rates, trans-epidermal water loss (TEWL) measurements, hydration, and blood perfusion levels, compared to cadaver skin-treated burn wounds. Pathology scoring indicated significant differences between the allograft- and IFSG-treated wounds on day 7, with the IFSG having increased angiogenesis, granulation tissue formation, and immune cells. Pathology scoring indicated no significant differences once mSTSGs were applied to wounds. The IFSG performed as well as cadaver skin as a temporary cover and was not inferior to the standard of care, suggesting the potential to transition IFSGs into clinical use for burns.
Full article
(This article belongs to the Topic Current Challenges and Advances in Skin Repair and Regeneration)
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Open AccessArticle
THZ2 Ameliorates Mouse Colitis and Colitis-Associated Colorectal Cancer
by
Sheng-Te Wang, Ying-Ying Wang, Jia-Rong Huang, Yu-Bin Shu, Ke He and Zhi Shi
Biomedicines 2024, 12(3), 679; https://doi.org/10.3390/biomedicines12030679 (registering DOI) - 18 Mar 2024
Abstract
Colorectal cancer is a global malignancy with a high incidence and mortality rate. THZ2, a small inhibitor targeted CDK7, could inhibit multiple human tumor growths including small cell lung cancer, triple-negative breast cancer, ovarian cancer. However, the effect of THZ2 on inflammation, especially
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Colorectal cancer is a global malignancy with a high incidence and mortality rate. THZ2, a small inhibitor targeted CDK7, could inhibit multiple human tumor growths including small cell lung cancer, triple-negative breast cancer, ovarian cancer. However, the effect of THZ2 on inflammation, especially on colitis-associated colorectal cancer, is still unknown. In this study, we assessed the anti-inflammatory and anti-tumor effect of THZ2 in the mouse models of dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer. We found that THZ2 ameliorated inflammatory symptoms, including bleeding and diarrhea, in mouse models of DSS-induced acute colitis and AOM/DSS-induced colorectal cancer. The results of Western blot and immunohistochemistry showed that THZ2 rescued the up-regulated expression of COX2, IL-6, β-catenin, and snail in the mouse models. Moreover, THZ2 inhibits the development of colorectal cancer in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer. Generally, THZ2 not only can inhibit DSS-induced colitis, but also can hinder AOM/DSS-induced colorectal cancer.
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(This article belongs to the Section Drug Metabolism)
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Open AccessArticle
Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus
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Xi Chen, Ying Song, Guanghui Chen, Baoliang Zhang, Yang Bai, Chuiguo Sun, Dongwei Fan and Zhongqiang Chen
Biomedicines 2024, 12(3), 678; https://doi.org/10.3390/biomedicines12030678 - 18 Mar 2024
Abstract
Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still
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Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca2+) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis.
Full article
(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)
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Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients
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Alessandra Della Vecchia, Ciro De Luca, Lucrezia Becattini, Letizia Curto, Elena Ferrari, Gabriele Siciliano, Sara Gori and Filippo Baldacci
Biomedicines 2024, 12(3), 677; https://doi.org/10.3390/biomedicines12030677 - 18 Mar 2024
Abstract
The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study
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The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.
Full article
(This article belongs to the Special Issue Crosstalk between Depression, Anxiety, Dementia, and Chronic Pain: Comorbidity in Behavioral Neurology and Neuropsychiatry Volume III)
Open AccessReview
The Use and Potential Benefits of N-Acetylcysteine in Non-Acetaminophen Acute Liver Failure: An Etiology-Based Review
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Mihai Popescu, Angelica Bratu, Mihaela Agapie, Tudor Borjog, Mugurel Jafal, Romina-Marina Sima and Carmen Orban
Biomedicines 2024, 12(3), 676; https://doi.org/10.3390/biomedicines12030676 - 18 Mar 2024
Abstract
Acute liver failure represents a life-threatening organ dysfunction with high mortality rates and an urgent need for liver transplantation. The etiology of the disease varies widely depending on various socio-economic factors and is represented mainly by paracetamol overdose and other drug-induced forms of
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Acute liver failure represents a life-threatening organ dysfunction with high mortality rates and an urgent need for liver transplantation. The etiology of the disease varies widely depending on various socio-economic factors and is represented mainly by paracetamol overdose and other drug-induced forms of liver dysfunction in the developed world and by viral hepatitis and mushroom poisoning in less developed countries. Current medical care constitutes either specific antidotes or supportive measures to ensure spontaneous recovery. Although it has been proven to have beneficial effects in paracetamol-induced liver failure, N-acetylcysteine is widely used for all forms of acute liver failure. Despite this, few well-designed studies have been conducted on the assessment of the potential benefits, dose regimens, or route of administration of N-acetylcysteine in non-acetaminophen liver failure. This review aims to summarize the current evidence behind the use of this drug in different forms of liver failure.
Full article
(This article belongs to the Special Issue Physiopathology and Pharmacology of the Gastrointestinal Tract)
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Current Knowledge on the Use of Neuromonitoring in Thyroid Surgery
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Beata Wojtczak, Karolina Sutkowska-Stępień, Mateusz Głód, Krzysztof Kaliszewski, Krzysztof Sutkowski and Marcin Barczyński
Biomedicines 2024, 12(3), 675; https://doi.org/10.3390/biomedicines12030675 - 18 Mar 2024
Abstract
Thyroid surgery rates have tripled over the past three decades, making it one of the most frequently performed procedures within general surgery. Thyroid surgery is associated with the possibility of serious postoperative complications which have a significant impact on the patient’s quality of
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Thyroid surgery rates have tripled over the past three decades, making it one of the most frequently performed procedures within general surgery. Thyroid surgery is associated with the possibility of serious postoperative complications which have a significant impact on the patient’s quality of life. Recurrent laryngeal nerve (RLN) palsy and external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and postoperative bleeding, some of the most common complications. The introduction of neuromonitoring into thyroid surgery, which enabled both the confirmation of anatomical integrity and the assessment of laryngeal nerve function, was a milestone that began a new era in thyroid surgery. The International Neural Monitoring Study Group has produced a standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery, which in turn increased the prevalence of neural monitoring during thyroidectomy. The current status of IONM and the benefits of its use have been presented in this publication.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessArticle
Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome
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Masroor Badshah, Jibriil Ibrahim, Nguok Su, Penny Whiley, Ralf Middendorff, Michael Whittaker and Betty Exintaris
Biomedicines 2024, 12(3), 674; https://doi.org/10.3390/biomedicines12030674 - 18 Mar 2024
Abstract
Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to the overexpression of oxytocin
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Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to the overexpression of oxytocin receptors (OXTRs) within the bladder detrusor muscle, resulting in increased baseline myogenic tone. Thus, it is hypothesised that targeting OXTRs within the bladder using oxytocin antagonists may attenuate myogenic tone within the bladder, thereby providing a new therapeutic avenue for treating OAB. Organ bath contractility and immunohistochemistry techniques were conducted on bladder tissue sourced from young rats (7–8 weeks and 10–12 weeks) and older rats (4–5 months and 7–9 months). Organ bath studies revealed that oxytocin (OT) significantly increased bladder contractions, which were significantly attenuated by [β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 µM) (**** p < 0.0001) and atosiban (10 µM) in both young and older rats (** p < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats (p ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** p < 0.001) and older rats (**** p < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** p < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** p < 0.01) and older rats (* p < 0.05), indicating OT may be a key modulator of bladder contractility.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessArticle
Cold Atmospheric Plasma Improves the Colonization of Titanium with Primary Human Osteoblasts: An In Vitro Study
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Madline P. Gund, Jusef Naim, Antje Lehmann, Matthias Hannig, Markus Lange, Axel Schindler and Stefan Rupf
Biomedicines 2024, 12(3), 673; https://doi.org/10.3390/biomedicines12030673 - 18 Mar 2024
Abstract
Several studies have shown that cold atmospheric plasma (CAP) treatment can favourably modify titanium surfaces to promote osteoblast colonization. The aim of this study was to investigate the initial attachment of primary human osteoblasts to plasma-treated titanium. Micro-structured titanium discs were treated with
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Several studies have shown that cold atmospheric plasma (CAP) treatment can favourably modify titanium surfaces to promote osteoblast colonization. The aim of this study was to investigate the initial attachment of primary human osteoblasts to plasma-treated titanium. Micro-structured titanium discs were treated with cold atmospheric plasma followed by the application of primary human osteoblasts. The microwave plasma source used in this study uses helium as a carrier gas and was developed at the Leibniz Institute for Surface Modification in Leipzig, Germany. Primary human osteoblasts were analyzed by fluorescence and cell biological tests (alkaline phosphatase activity and cell proliferation using WST-1 assay). The tests were performed after 4, 12, and 24 h and showed statistically significant increased levels of cell activity after plasma treatment. The results of this study indicate that plasma treatment improves the initial attachment of primary human osteoblasts to titanium. For the first time, the positive effect of cold atmospheric plasma treatment of micro-structured titanium on the initial colonization with primary human osteoblasts has been demonstrated. Overall, this study demonstrates the excellent biocompatibility of micro-structured titanium. The results of this study support efforts to use cold atmospheric plasmas in implantology, both for preimplantation conditioning and for regeneration of lost attachment due to peri-implantitis.
Full article
(This article belongs to the Special Issue Plasma Applications in Biomedicine)
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Open AccessArticle
Connections between Cognitive Impairment and Atrial Fibrillation in Patients with Diabetes Mellitus Type 2
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Marius Militaru, Daniel Florin Lighezan, Cristina Tudoran and Anda Gabriela Militaru
Biomedicines 2024, 12(3), 672; https://doi.org/10.3390/biomedicines12030672 - 17 Mar 2024
Abstract
(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research
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(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research if the association of DM-2 and AF favors a precocious onset of CD. (2) Methods: This study was conducted on 160 patients, featuring 50 with DM-2, 54 with DM-2 and AF, and 56 subjects without DM-2 and AF, all evaluated clinically and with five neuropsychiatric scales. (3) Results: The Mini-Mental-State-Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living Score (ADL), Instrumental Activities of Daily Living Score (IADL), and Geriatric Depression Scale (GDS-15) were significantly altered in patients with DM-2 and AF in comparison to patients without these diseases. The logistic regression model indicated that, in patients with DM-2 and AF, an increase of one year in age is associated with a 7.3% augmentation of the risk of a precocious onset of CD (MMSE < 27). (4) Conclusions: CD is more frequent in patients with DM-2, especially when associated with AF, versus those without DM-2 and AF. Our findings suggest that an older age and associated dyslipidemia represent risk factors for CD in patients with DM-2.
Full article
(This article belongs to the Special Issue Pathomechanisms of Disturbances Underlying Chronic Disorders—2nd Edition)
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Correlation between Different Psychological Variables in Women with Fibromyalgia with Symptoms of Neurogenic Inflammation: A Cross-Sectional Study
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Víctor Riquelme-Aguado, Alazne Zabarte-del Campo, Guillermo Baviano-Klett, Josué Fernández-Carnero, Antonio Gil-Crujera and Francisco Gómez-Esquer
Biomedicines 2024, 12(3), 671; https://doi.org/10.3390/biomedicines12030671 - 17 Mar 2024
Abstract
Fibromyalgia (FM) is a chronic pain syndrome hypothesized to arise from a state of neurogenic inflammation. Mechanisms responsible for pain, as well as psychological variables, are typically altered in this condition. The main objective of this research was to explore somatosensory and psychological
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Fibromyalgia (FM) is a chronic pain syndrome hypothesized to arise from a state of neurogenic inflammation. Mechanisms responsible for pain, as well as psychological variables, are typically altered in this condition. The main objective of this research was to explore somatosensory and psychological alterations in women with FM. The secondary objective was to carry out a secondary analysis to correlate the different variables studied and delve into the influences between them. The relationship between different psychological variables in fibromyalgia is not clear in the previous scientific literature. Forty-four individuals participated, of which twenty-two were controls and twenty-two were women with fibromyalgia. The main outcome measures were the Numeric Pain Rating Scale, Fibromyalgia Impact Questionnaire, pressure pain threshold, conditioned pain modulation, anxiety and depression symptoms, catastrophizing and kinesiophobia cognitions. The main analysis showed that there is a moderate correlation between the psychological variables of depression and fear of movement and the ability to modulate pain. There is also a moderately inverse correlation between pain catastrophizing cognitions and pain intensity/disability. Multiple moderate and strong correlations were found among the various psychological variables studied. FM patients exhibit somatosensory alterations alongside negative psychological symptoms that influence the experience of pain, and they may perpetuate the state of neurogenic inflammation.
Full article
(This article belongs to the Collection Neurogenic Neuroinflammation in Fibromyalgia)
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Open AccessArticle
Can Repetitive Transcranial Magnetic Stimulation (rTMS) Promote Neurogenesis and Axonogenesis in Subacute Human Ischemic Stroke?
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Manuela De Michele, Paola Piscopo, Matteo Costanzo, Svetlana Lorenzano, Alessio Crestini, Roberto Rivabene, Valeria Manzini, Luca Petraglia, Marta Iacobucci, Irene Berto, Oscar Gaetano Schiavo, Antonella Conte, Daniele Belvisi, Alfredo Berardelli and Danilo Toni
Biomedicines 2024, 12(3), 670; https://doi.org/10.3390/biomedicines12030670 - 17 Mar 2024
Abstract
Background: Ischemic stroke may trigger neuroplastic changes via proliferation, migration towards the lesion, and differentiation of neuroprogenitor cells into mature neurons. Repetitive Transcranial Magnetic Stimulation (rTMS) may promote brain plasticity. This study aimed to assess rTMS’s effect on post-stroke endogenous neuroplasticity by dosing
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Background: Ischemic stroke may trigger neuroplastic changes via proliferation, migration towards the lesion, and differentiation of neuroprogenitor cells into mature neurons. Repetitive Transcranial Magnetic Stimulation (rTMS) may promote brain plasticity. This study aimed to assess rTMS’s effect on post-stroke endogenous neuroplasticity by dosing plasma miRs 17~92, Netrin-1, Sema3A, and BDNF. Methods: In this case-controlled study, we randomized 19 ischemic stroke patients within five days from symptoms onset (T0) to neuronavigated-rTMS or sham stimulation. Stimulation was applied on the stroke hemisphere daily between the 7th and 14th day from stroke onset. Blood samples were collected at T0, before the first rTMS section (T7), and at the end of the last rTMS session (T14). Five healthy controls were also enrolled in this study. Results: Of 19 patients, 10 received rTMS and 9 sham stimulation. Compared with the sham group, in the rTMS group, plasma levels of miRs17~92 and Ntn-1 significantly increased whereas Sema3A levels tended to decrease. In multivariate linear regression analyses, rTMS was independently related to Ntn-1 and miR-25 levels at T14. Conclusions: We found an association between rTMS and neurogenesis/axonogenesis biomarker enhancement. Our preliminary data suggest that rTMS may positively interfere with natural endogenous plasticity phenomena of the post-ischemic human brain.
Full article
(This article belongs to the Section Neurobiology and Neurologic Disease)
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Open AccessReview
Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma
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Piotr J. Błoński, Anna M. Czarnecka, Krzysztof Ostaszewski, Anna Szumera-Ciećkiewicz and Piotr Rutkowski
Biomedicines 2024, 12(3), 669; https://doi.org/10.3390/biomedicines12030669 - 17 Mar 2024
Abstract
Neoadjuvant systemic therapy is emerging as the best medical practice in patients with resectable stage III melanoma. As different regimens are expected to become available in this approach, the improved optimization of treatment strategies is required. Personalization of care in each individual patient—by
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Neoadjuvant systemic therapy is emerging as the best medical practice in patients with resectable stage III melanoma. As different regimens are expected to become available in this approach, the improved optimization of treatment strategies is required. Personalization of care in each individual patient—by precisely determining the disease-related risk and the most efficient therapeutic approach—is expected to minimize disease recurrence, but also the incidence of treatment-related adverse events and the extent of surgical intervention. This can be achieved through validation and clinical application of predictive and prognostic biomarkers. For immune checkpoint inhibitors, there are no validated predictive biomarkers until now. Promising predictive molecular biomarkers for neoadjuvant immunotherapy are tumor mutational burden and the interferon-gamma pathway expression signature. Pathological response to neoadjuvant treatment is a biomarker of a favorable prognosis and surrogate endpoint for recurrence-free survival in clinical trials. Despite the reliability of these biomarkers, risk stratification and response prediction in the neoadjuvant setting are still unsatisfactory and represent a critical knowledge gap, limiting the development of optimized personalized strategies in everyday practice.
Full article
(This article belongs to the Special Issue Melanoma: Epigenetic Modification, Molecular Changes, and Precision Targeting)
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Open AccessReview
Subepithelial Stromal Cells: Their Roles and Interactions with Intestinal Epithelial Cells during Gut Mucosal Homeostasis and Regeneration
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Hammed Ayansola, Edith J. Mayorga and Younggeon Jin
Biomedicines 2024, 12(3), 668; https://doi.org/10.3390/biomedicines12030668 - 17 Mar 2024
Abstract
Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging. This difficulty is due to the lack of specific markers
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Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging. This difficulty is due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Consequently, it is imperative to understand the cellular pathways that regulate their activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration after mucosal injury. This review provides insights into the spatial distribution and functions of identified iMSC subtypes. It focuses on their involvement in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries.
Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells and Their Cellular Interactions)
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Open AccessArticle
The Cytological Energy Detection of Purulent Inflammation in Synovial Fluid Is Not All Black and White
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Petr Kelbich, Eliska Vanaskova, Karel Hrach, Jan Krejsek, Frantisek Smisko, Pavla Hruskova, Eva Hanuljakova and Tomas Novotny
Biomedicines 2024, 12(3), 667; https://doi.org/10.3390/biomedicines12030667 - 16 Mar 2024
Abstract
Neutrophils are frequently found in the cytological picture of synovial fluid in several joint pathologies, and a higher proportion of them can even wrongly indicate these cases as purulent inflammation. For reliable differentiation between purulent and non-purulent cases, we use the cytological energy
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Neutrophils are frequently found in the cytological picture of synovial fluid in several joint pathologies, and a higher proportion of them can even wrongly indicate these cases as purulent inflammation. For reliable differentiation between purulent and non-purulent cases, we use the cytological energy analysis of the synovial fluid. Using this method, we examined 350 knee joint synovial fluid samples. Overall, we found that the percentage of neutrophils ranged between 20.0% and 50.0% in 44 (12.6%) cases and was above 50.0% in 231 (66.0%) cases. In the same group, only 85 (24.3%) highly anaerobic synovial fluid samples were evaluated as purulent inflammation, and another 17 (4.9%) cases were evaluated as very likely purulent inflammation. Further, we quantified the immediate risk of purulent inflammation using the “purulent score” (PS). Of the total of 350 samples, 103 (29.4%) cases were classified as having a very high risk of purulent inflammation (PS = 4), 53 (15.1%) cases were classified as having a significant risk of purulent inflammation (PS = 3), 17 (4.9%) cases were classified as having a moderate risk of purulent inflammation (PS = 2), and 75 (21.4%) cases were classified as having no immediate risk of purulent inflammation (PS = 1). Based on our results and analyses, the cytological energy analysis of synovial fluid is an effective method that can be used to detect and specify joint inflammation and the risk of septic arthritis development.
Full article
(This article belongs to the Special Issue Neutrophils in Immunity and Diseases)
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Open AccessArticle
Performance of Radiological and Biochemical Biomarkers in Predicting Radio-Symptomatic Knee Osteoarthritis Progression
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Ahmad Almhdie-Imjabbar, Hechmi Toumi and Eric Lespessailles
Biomedicines 2024, 12(3), 666; https://doi.org/10.3390/biomedicines12030666 - 16 Mar 2024
Abstract
Imaging biomarkers permit improved approaches to identify the most at-risk patients encountering knee osteoarthritis (KOA) progression. This study aimed to investigate the utility of trabecular bone texture (TBT) extracted from plain radiographs, associated with a set of clinical, biochemical, and radiographic data, as
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Imaging biomarkers permit improved approaches to identify the most at-risk patients encountering knee osteoarthritis (KOA) progression. This study aimed to investigate the utility of trabecular bone texture (TBT) extracted from plain radiographs, associated with a set of clinical, biochemical, and radiographic data, as a predictor of long-term radiographic KOA progression. We used data from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium dataset. The reference model made use of baseline TBT parameters adjusted for clinical covariates and radiological scores. Several models based on a combination of baseline and 24-month TBT variations (TBT∆TBT) were developed using logistic regression and compared to those based on baseline-only TBT parameters. All models were adjusted for baseline clinical covariates, radiological scores, and biochemical descriptors. The best overall performances for the prediction of radio-symptomatic, radiographic, and symptomatic progression were achieved using TBT∆TBT parameters solely, with area under the ROC curve values of 0.658 (95% CI: 0.612–0.705), 0.752 (95% CI: 0.700–0.804), and 0.698 (95% CI: 0.641–0.756), respectively. Adding biochemical markers did not significantly improve the performance of the TBT∆TBT-based model. Additionally, when TBT values were taken from the entire subchondral bone rather than just the medial, lateral, or central compartments, better results were obtained.
Full article
(This article belongs to the Special Issue Osteoarthritis and Associated Pain: Molecular Research and Novel Therapeutic Approaches)
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Open AccessReview
High Hopes for the Biofabrication of Articular Cartilage—What Lies beyond the Horizon of Tissue Engineering and 3D Bioprinting?
by
Yordan Sbirkov, Murad Redzheb, Nico Forraz, Colin McGuckin and Victoria Sarafian
Biomedicines 2024, 12(3), 665; https://doi.org/10.3390/biomedicines12030665 - 15 Mar 2024
Abstract
Technologies and biomaterials for 3D bioprinting have been developing extremely quickly in the past decade as they hold great potential in tissue engineering. This, together with the possibility to differentiate stem cells of different origin into any cell type, raises the hopes in
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Technologies and biomaterials for 3D bioprinting have been developing extremely quickly in the past decade as they hold great potential in tissue engineering. This, together with the possibility to differentiate stem cells of different origin into any cell type, raises the hopes in regenerative medicine once again after the initial breakthrough with stem cells in the 1980s. Nevertheless, three decades of 3D bioprinting experiments have shown that the production of functional tissues would take a longer time than anticipated. Cartilage, one of the simplest tissues in the body, consists of only one cell type. It is not vascularised and innervated and does not have lymphatic vessels either, which makes it a perfect target tissue for successful implantation. The tremendous amount of work since the beginning of this century, combining the efforts of bioengineers, material scientists, biologists, and physicians, has culminated in multiple proof-of-concept constructs that have been implanted in animals. However, there is no single reproducible, standardised, widely accessible and accepted strategy that can be readily applied in the clinic. In this review, we focus on the current progress in the field of the 3D biofabrication of articular cartilage and critically assess failures and future challenges.
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(This article belongs to the Special Issue Tissue Engineering and Cell Therapy for Cartilage Repair)
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Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies
by
Wenkai Shao, Ping Wang, Xiao Lv, Bo Wang, Song Gong and Yong Feng
Biomedicines 2024, 12(3), 664; https://doi.org/10.3390/biomedicines12030664 - 15 Mar 2024
Abstract
Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most
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Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.
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(This article belongs to the Special Issue Endothelial Dysfunction: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory–Motor Cortical Stroke
by
Jessica M. Livingston, Tina T. Lee, Tom Enbar, Emerson Daniele, Clara M. Phillips, Alexandra Krassikova, K. W. Annie Bang, Ines Kortebi, Brennan W. Donville, Omadyor S. Ibragimov, Nadia Sachewsky, Daniela Lozano Casasbuenas, Arman Olfat and Cindi M. Morshead
Biomedicines 2024, 12(3), 663; https://doi.org/10.3390/biomedicines12030663 - 15 Mar 2024
Abstract
Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate
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Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory–motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.
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(This article belongs to the Special Issue Novel Approaches to the Regeneration and Repair of the Nervous System: Neuronal Reprogramming)
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Ceruloplasmin, Catalase and Creatinine Concentrations Are Independently Associated with All-Cause Mortality in Patients with Advanced Heart Failure
by
Wiktoria Smyła-Gruca, Wioletta Szczurek-Wasilewicz, Michał Skrzypek, Andrzej Karmański, Ewa Romuk, Michał Jurkiewicz, Mariusz Gąsior and Bożena Szyguła-Jurkiewicz
Biomedicines 2024, 12(3), 662; https://doi.org/10.3390/biomedicines12030662 - 15 Mar 2024
Abstract
The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed
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The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed 85 heart transplant candidates who were hospitalized at our institution for right heart catheterization. Ten milliliters of coronary sinus blood was collected to measure oxidative/antioxidative markers. The median age was 58 (50–62) years, and 90.6% of them were male. The one-year mortality rate was 40%. Multivariable logistic regression analysis revealed that ceruloplasmin (OR = 1.342 [1.019–1.770], p = 0.0363; per unit decrease), catalase (OR = 1.053 [1.014–1.093], p = 0.0076; per unit decrease), and creatinine (OR = 1.071 [1.002–1.144], p = 0.0422; per unit increase) were independently associated with one-year mortality. Ceruloplasmin, catalase, and creatinine had areas under the curve of 0.9296 [0.8738–0.9855], 0.9666 [0.9360–0.9971], and 0.7682 [0.6607–0.8756], respectively. Lower ceruloplasmin and catalase in the coronary sinus, as well as higher creatinine in peripheral blood, are independently associated with one-year mortality in patients with advanced HF. Catalase and ceruloplasmin have excellent prognostic power, and creatinine has acceptable prognostic power, allowing the distinction of one-year survivors from nonsurvivors.
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(This article belongs to the Section Molecular and Translational Medicine)
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YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration
by
Youzhi Wang, Ning Wu, Junbo Li, Diansheng Zhou, Jiaming Liang, Qian Cao, Zhaokai Guan, Yangyang Xu and Ning Jiang
Biomedicines 2024, 12(3), 661; https://doi.org/10.3390/biomedicines12030661 - 15 Mar 2024
Abstract
The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions
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The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).
Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines in Cancer Progression 2.0)
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