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
Mesenchymal Stem Cells Reduce the Extracellular Mitochondrial DNA-Mediated TLR9 Activation in Neonatal Hyperoxia-Induced Lung Injury
Biomedicines 2024, 12(3), 686; https://doi.org/10.3390/biomedicines12030686 (registering DOI) - 19 Mar 2024
Abstract
Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that
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Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that the level of extracellular mtDNA would be increased after hyperoxia-induced lung injury but reduced after lung injury attenuation by MSC therapy in our newborn rat model. In an in vitro study using a rat lung epithelial L2 cell line, we found that the level of extracellular mtDNA was significantly increased with H2O2-induced cell death but reduced after MSC co-incubation. In an in vivo study, we confirmed that the levels of cell death, extracellular mtDNA, and inflammatory cytokines were significantly increased in hyperoxic newborn rat lungs but reduced after MSC transplantation. The levels of extracellular mtDNA were significantly and positively correlated with the levels of the inflammatory cytokines. The TLR9/MyD88/NF-κB pathway, which is activated by binding to mtDNA, was also significantly upregulated but downregulated after MSC transplantation. We found a significant positive correlation between inflammatory cytokines and extracellular mtDNA in intubated neonates. The levels of inflammatory cytokines and extracellular mtDNA changed over time in a similar pattern in transtracheal aspirate samples from intubated neonates. In conclusion, increased levels of extracellular mtDNA are associated with increased inflammation in hyperoxia-induced lung injury, and attenuation of lung inflammation by MSC therapy is associated with reduced levels of extracellular mtDNA.
Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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Linking Periodontitis with Inflammatory Bowel Disease through the Oral–Gut Axis: The Potential Role of Porphyromonas gingivalis
by
Xinyi Huang, Yilin Li, Jun Zhang and Qiang Feng
Biomedicines 2024, 12(3), 685; https://doi.org/10.3390/biomedicines12030685 (registering DOI) - 19 Mar 2024
Abstract
Periodontitis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases that are characterized by abnormal host immune responses and microbiota dysbiosis. Emerging evidence implies potential associations between periodontitis and IBD. Porphyromonas gingivalis (P. gingivalis), a primary cause of periodontitis, is
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Periodontitis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases that are characterized by abnormal host immune responses and microbiota dysbiosis. Emerging evidence implies potential associations between periodontitis and IBD. Porphyromonas gingivalis (P. gingivalis), a primary cause of periodontitis, is thought to play a role in the development of IBD through the oral–gut disease axis. However, the precise mechanisms of its involvement remain enigmatic. In this narrative review, we begin with a discussion of the bidirectional relationship between periodontitis and IBD and the involvement of P. gingivalis in each of the two diseases. Further, we summarize the possible routes by which P. gingivalis links periodontitis and IBD through the oral–gut axis, as well as the underlying mechanisms of its involvement in the pathogenesis of IBD. Collectively, P. gingivalis participates in the progression of IBD through gut dysbiosis, impairment of the intestinal barrier, release of inflammatory mediators, and disturbance of the immune response. The above findings may provide new insights for exploring novel biomarkers and potential therapeutic approaches for IBD.
Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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Open AccessArticle
Melatonin Decreases Alveolar Bone Loss in Rats with Experimental Periodontitis and Osteoporosis: A Morphometric and Histopathologic Study
by
Suat Serhan Altıntepe Doğan, Hülya Toker and Ömer Fahrettin Göze
Biomedicines 2024, 12(3), 684; https://doi.org/10.3390/biomedicines12030684 - 19 Mar 2024
Abstract
Background: Periodontitis and post-menopausal osteoporosis include common chronic bone disorders worldwide, with similar etiopathogenetic events. This study evaluated the effect of systemic melatonin administration on the alveolar bone destruction of periodontitis progression in an experimental periodontitis model in osteoporotic rats. Methods: Forty-four Wistar
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Background: Periodontitis and post-menopausal osteoporosis include common chronic bone disorders worldwide, with similar etiopathogenetic events. This study evaluated the effect of systemic melatonin administration on the alveolar bone destruction of periodontitis progression in an experimental periodontitis model in osteoporotic rats. Methods: Forty-four Wistar rats were randomly divided into six experimental groups: control (C; n = 6); osteoporosis (O; n = 6); ligated periodontitis (LP; n = 8); osteoporosis- and periodontitis-induced (O+LP; n = 8); osteoporosis- and periodontitis-induced through 30 mg/kg/day melatonin administration (ML30; n = 8); and osteoporosis- and periodontitis-induced through 50 mg/kg/day melatonin administration (ML50; n = 8). The rats underwent bilateraloophorectomy and were maintained for 4 months to induce osteoporosis. After 4 months, 4-0 silk ligatures were placed submarginally around the mandibular first molar of each rat to induce experimental periodontitis, and melatonin was administered in the ML30 and ML50 groups for 30 days. Changes in alveolar bone levels were clinically measured, and tissues were histopathologically examined. Results: Osteoclastic activity in the LP and O+LP groups was significantly higher than in the other groups (p < 0.05), but was similar in the C, O, and ML30 groups (p > 0.05). RANKL activity was the highest in the O+LP group, while melatonin decreased RANKL activity in the melatonin-administered groups (p < 0.05). Systemically administered melatonin significantly decreased alveolar bone loss in the ML30 and ML50 groups compared with that in the periodontitis groups (p < 0.05). Conclusions: Melatonin inhibited alveolar bone destruction by decreasing the RANKL expression and inflammatory cell infiltration and increased osteoblastic activity in a rat model with osteoporosis and periodontitis.
Full article
(This article belongs to the Topic Animal Model in Biomedical Research, 2nd Volume)
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Open AccessReview
Advancements in Spinal Cord Injury Repair: Insights from Dental-Derived Stem Cells
by
Xueying Wen, Wenkai Jiang, Xiaolin Li, Qian Liu, Yuanyuan Kang and Bing Song
Biomedicines 2024, 12(3), 683; https://doi.org/10.3390/biomedicines12030683 - 19 Mar 2024
Abstract
Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells
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Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSCs), are of interest due to their accessibility, minimally invasive extraction, and robust differentiating capabilities. Research indicates their potential to differentiate into neural cells and promote SCI repair in animal models at both tissue and functional levels. This review explores the potential applications of dental-derived stem cells in SCI neural repair, covering stem cell transplantation, conditioned culture medium injection, bioengineered delivery systems, exosomes, extracellular vesicle treatments, and combined therapies. Assessing the clinical effectiveness of dental-derived stem cells in the treatment of SCI, further research is necessary. This includes investigating potential biological mechanisms and conducting Large-animal studies and clinical trials. It is also important to undertake more comprehensive comparisons, optimize the selection of dental-derived stem cell types, and implement a functionalized delivery system. These efforts will enhance the therapeutic potential of dental-derived stem cells for repairing SCI.
Full article
(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)
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Open AccessReview
Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future
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Mohammed Tiseer Abbas, Nima Baba Ali, Juan M. Farina, Ahmed K. Mahmoud, Milagros Pereyra, Isabel G. Scalia, Moaz A. Kamel, Timothy Barry, Steven J. Lester, Charles R. Cannan, Rohit Mital, Susan Wilansky, William K. Freeman, Chieh-Ju Chao, Said Alsidawi, Chadi Ayoub and Reza Arsanjani
Biomedicines 2024, 12(3), 682; https://doi.org/10.3390/biomedicines12030682 - 19 Mar 2024
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core
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Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.
Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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Open AccessReview
Macroscopic and Microscopic Cerebral Findings in Drug and Alcohol Abusers: The Point of View of the Forensic Pathologist
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Angelo Montana, Letizia Alfieri, Margherita Neri, Denise Piano, Eva Renier, Matteo Marti, Marco Palpacelli, Giovanni Tossetta and Francesco Paolo Busardò
Biomedicines 2024, 12(3), 681; https://doi.org/10.3390/biomedicines12030681 - 19 Mar 2024
Abstract
Drug abuse still represents a significant challenge for forensic pathologists; it must always be considered during the autopsy examination when the brain morphological alterations observed are not characteristic of any known disease of the central nervous system (CNS). Nonetheless, no specific brain lesions
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Drug abuse still represents a significant challenge for forensic pathologists; it must always be considered during the autopsy examination when the brain morphological alterations observed are not characteristic of any known disease of the central nervous system (CNS). Nonetheless, no specific brain lesions had been found to characterize the precise drug that caused the poisoning. In fact, a broad spectrum of changes affecting the CNS are seen in drug abusers. Thus, forensic pathology plays a key role in identifying the encephalic morphological alterations underlying the death. The aim of this review is to present an updated overview of the literature regarding the correlation between the main substances of abuse and the morphological alterations of the CNS to help the forensic pathologist to discriminate drug-induced alterations of the brain. The authors used the PRISMA criteriology to perform the bibliographic search for the present review. Among the articles identified according to the selected search criteria, 116 articles were chosen which allow us to define a picture of the main macroscopic and microscopic alterations of the brain in drug abuse.
Full article
(This article belongs to the Special Issue Molecular Research in Substance Abuse: Toxicity, Neurotoxicity and Neuropathological Findings)
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Open AccessArticle
Comparison of Intact Fish Skin Graft and Allograft as Temporary Coverage for Full-Thickness Burns: A Non-Inferiority Study
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Randolph Stone II, Emily C. Saathoff, David A. Larson, John T. Wall, Nathan A. Wienandt, Skuli Magnusson, Hilmar Kjartansson, Robert J. Christy and Shanmugasundaram Natesan
Biomedicines 2024, 12(3), 680; https://doi.org/10.3390/biomedicines12030680 - 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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THZ2 Ameliorates Mouse Colitis and Colitis-Associated Colorectal Cancer
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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 - 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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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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Open AccessReview
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.
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(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.
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(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
by
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.
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(This article belongs to the Collection Neurogenic Neuroinflammation in Fibromyalgia)
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Can Repetitive Transcranial Magnetic Stimulation (rTMS) Promote Neurogenesis and Axonogenesis in Subacute Human Ischemic Stroke?
by
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.
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(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
by
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.
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(This article belongs to the Special Issue Melanoma: Epigenetic Modification, Molecular Changes, and Precision Targeting)
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Subepithelial Stromal Cells: Their Roles and Interactions with Intestinal Epithelial Cells during Gut Mucosal Homeostasis and Regeneration
by
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.
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(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells and Their Cellular Interactions)
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The Cytological Energy Detection of Purulent Inflammation in Synovial Fluid Is Not All Black and White
by
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.
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(This article belongs to the Special Issue Neutrophils in Immunity and Diseases)
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