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
Vitamin D Levels in COVID-19 and NonCOVID-19 Pediatric Patients and Its Relationship with Clinical and Laboratory Characteristics
Biomedicines 2024, 12(4), 905; https://doi.org/10.3390/biomedicines12040905 - 18 Apr 2024
Abstract
25-hydroxyvitamin D [25(OH)D] is a marker with an important role in regulating the inflammatory response. Low concentrations of this vitamin are often found among the population, correlated with increased risk of respiratory tract infections. The aim of the study is to evaluate the
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25-hydroxyvitamin D [25(OH)D] is a marker with an important role in regulating the inflammatory response. Low concentrations of this vitamin are often found among the population, correlated with increased risk of respiratory tract infections. The aim of the study is to evaluate the relationship between vitamin D levels and clinical and laboratory markers in children and adolescents hospitalized with and without COVID-19. A retrospective study, including all patients tested for SARS-CoV-2 and having vitamin D measured, was performed. All included hospitalized cases, 78 COVID-19 patients and 162 NonCOVID-19 patients, were divided into subgroups according to their 25(OH)D serum levels (<20 ng/mL—deficiency, 20–30 ng/mL—insufficiency, ≥30 ng/mL—normal or <30 ng/mL, ≥30 ng/mL) and age (≤2 years, >2 years). Vitamin D deficiency and insufficiency increased with age, in both COVID-19 and NonCOVID-19 groups. All symptoms were encountered more frequently in cases of pediatric patients with COVID-19 in comparison with NonCOVID-19 cases. The most frequently encountered symptoms in the COVID-19 group were fever, loss of appetite, and nasal congestion. In the NonCOVID-19 group, serum 25(OH)D concentrations were positively correlated with leukocytes, lymphocytes, and LMR and negatively correlated with neutrophils, NLR, and PLR while no significant correlation was observed in the case of COVID-19 group. Differences between vitamin D status and clinical and laboratory parameters were observed, but their clinical significance should be interpreted with caution. The results of this study may offer further support for future studies exploring the mechanisms of the relationship between vitamin D and clinical and laboratory markers as well as for studies investigating the implications of vitamin D deficiency/supplementation on overall health/clinical outcomes of patients with/without COVID-19.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
Open AccessArticle
Verapamil Attenuates the Severity of Tendinopathy by Mitigating Mitochondrial Dysfunction through the Activation of the Nrf2/HO-1 Pathway
by
Zengguang Wang, Zhenglin Dong, Yiming Li, Xin Jiao, Yihao Liu, Hanwen Chang and Yaokai Gan
Biomedicines 2024, 12(4), 904; https://doi.org/10.3390/biomedicines12040904 - 18 Apr 2024
Abstract
Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This
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Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL−1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL−1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.
Full article
(This article belongs to the Section Gene and Cell Therapy)
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Open AccessArticle
The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer
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Se Jun Park, Ju Yeon Park, Kabsoo Shin, Tae Ho Hong, Younghoon Kim, In-Ho Kim and MyungAh Lee
Biomedicines 2024, 12(4), 903; https://doi.org/10.3390/biomedicines12040903 - 18 Apr 2024
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77
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Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6’s role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.
Full article
(This article belongs to the Special Issue Past, Present and Further Looking for Therapeutic Management of Pancreatic Ductal Adenocarcinoma)
Open AccessArticle
N-Acetylcysteine Attenuates Sepsis-Induced Muscle Atrophy by Downregulating Endoplasmic Reticulum Stress
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Renyu Chen, Yingfang Zheng, Chenchen Zhou, Hongkai Dai, Yurou Wang, Yun Chu and Jinlong Luo
Biomedicines 2024, 12(4), 902; https://doi.org/10.3390/biomedicines12040902 - 18 Apr 2024
Abstract
(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused
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(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused by several diseases, whereas its effect on sepsis-induced muscle atrophy has not been reported. The present study investigated the effect of NAC on sepsis-induced muscle atrophy and its possible mechanisms. (2) Methods: The effect of NAC on sepsis-induced muscle atrophy was assessed in vivo and in vitro using cecal ligation and puncture-operated (CLP) C57BL/6 mice and LPS-treated C2C12 myotubes. We used immunofluorescence staining to analyze changes in the cross-sectional area (CSA) of myofibers in mice and the myotube diameter of C2C12. Protein expressions were analyzed by Western blotting. (3) Results: In the septic mice, the atrophic response manifested as a reduction in skeletal muscle weight and myofiber cross-sectional area, which is mediated by muscle-specific ubiquitin ligases—muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle ring finger 1 (MuRF1). NAC alleviated sepsis-induced skeletal muscle wasting and LPS-induced C2C12 myotube atrophy. Meanwhile, NAC inhibited the sepsis-induced activation of the endoplasmic reticulum (ER) stress signaling pathway. Furthermore, using 4-Phenylbutyric acid (4-PBA) to inhibit ER stress in LPS-treated C2C12 myotubes could partly abrogate the anti-muscle-atrophy effect of NAC. Finally, NAC alleviated myotube atrophy induced by the ER stress agonist Thapsigargin (Thap). (4) Conclusions: NAC can attenuate sepsis-induced muscle atrophy, which may be related to downregulating ER stress.
Full article
(This article belongs to the Section Immunology and Immunotherapy)
Open AccessArticle
Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes
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Meetakshi Gupta, Mustafa Anjari, Sebastian Brandner, Naomi Fersht, Elena Wilson, Steffi C Thust and Michael Kosmin
Biomedicines 2024, 12(4), 901; https://doi.org/10.3390/biomedicines12040901 - 18 Apr 2024
Abstract
Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3
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Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.
Full article
(This article belongs to the Special Issue Glioblastoma: Current Status and Future Prospects)
Open AccessReview
What Is the Role of Basal Weekly Insulin in Clinical Practice? The State of the Art
by
Christiano Argano, Laura Priola, Francesco Manno and Salvatore Corrao
Biomedicines 2024, 12(4), 900; https://doi.org/10.3390/biomedicines12040900 - 18 Apr 2024
Abstract
Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in
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Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in type 2 diabetes mellitus (T2DM), as the only replacement therapy in type 1 diabetes mellitus (T1DM) and also in gestational diabetes. In this context, the study of molecules such as weekly basal insulins, both for their technological and pharmacodynamic innovation and their manageability and undoubted benefits in compliance with drug therapy, can only be a turning point in diabetes and for all its phenotypes. This review aims to provide insight into the knowledge of basal weekly insulins and their use in type 1 and 2 diabetes mellitus by examining their safety, efficacy, manageability and increased therapeutic compliance.
Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
Open AccessArticle
Optimal Volume Assessment for Serous Fluid Cytology
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Konstantinos Christofidis, Maria Theochari, Stylianos Mavropoulos Papoudas, Lamprini Kiohou, Stylianos Sousouris, Areti Dimitriadou, Nikolaos Volakakis, Nicoletta Maounis and Panagiota Mikou
Biomedicines 2024, 12(4), 899; https://doi.org/10.3390/biomedicines12040899 - 18 Apr 2024
Abstract
Objective: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories
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Objective: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. Methods: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. Results: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. Conclusions: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.
Full article
(This article belongs to the Special Issue Next Generation Cytopathology: Current Status and Future Prospects)
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Open AccessSystematic Review
The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: A Systematic Review
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João Estarreja, Gonçalo Caldeira, Inês Silva, Priscila Mendes and Vanessa Mateus
Biomedicines 2024, 12(4), 898; https://doi.org/10.3390/biomedicines12040898 - 18 Apr 2024
Abstract
Background: Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin
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Background: Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin through its use in animal models of disease. Nevertheless, there is no consensus about the underlying mechanism(s) and the most optimal therapeutic regimens. Therefore, this review aims to summarize, analyze, and discuss the current preclinical evidence concerning the pharmacological effect of hemin. Methods: Following the application of the search expression and the retrieval of the articles, only nonclinical studies in vivo written in English were considered, where the potential anti-inflammatory effect of hemin was evaluated. Results: Forty-nine articles were included according to the eligibility criteria established. The results obtained show the preference of using 30 to 50 mg/kg of hemin, administered intraperitoneally, in both acute and chronic contexts. This drug demonstrates significant anti-inflammatory and antioxidant activities considering its capacity for reducing the expression of proinflammatory and oxidative markers. Conclusions: This review highlighted the significant anti-inflammatory and antioxidant effects of hemin, providing a clearer vision for the medical community about the use of this drug in several human diseases.
Full article
(This article belongs to the Special Issue Molecular Mechanism in Inflammation and Immunity)
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Open AccessArticle
No Impact of Enteral Nutrition on Fecal Short-Chain Fatty Acids in Children with Cerebral Palsy
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Dorota Mickiewicz-Góra, Katarzyna Sznurkowska, Arleta Drozd, Anna Borkowska, Maciej Zagierski, Joanna Troch, Karolina Skonieczna-Żydecka and Agnieszka Szlagatys-Sidorkiewicz
Biomedicines 2024, 12(4), 897; https://doi.org/10.3390/biomedicines12040897 - 18 Apr 2024
Abstract
Bacteria can impact the host organism through their metabolites, with short-chain fatty acids (SCFAs) being the most important, including acetate (C2), propionate (C3), butyrate (C4), valerate (C5n), and isovalerate (C5i). This study aimed to identify the impact of enteral nutrition on SCFAs in
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Bacteria can impact the host organism through their metabolites, with short-chain fatty acids (SCFAs) being the most important, including acetate (C2), propionate (C3), butyrate (C4), valerate (C5n), and isovalerate (C5i). This study aimed to identify the impact of enteral nutrition on SCFAs in children with cerebral palsy and to test the hypothesis that the type of nutrition in cerebral palsy affects gut SCFA levels. Cerebral palsy is a heterogeneous syndrome resulting from non-progressive damage to the central nervous system. The study group included 30 children diagnosed with cerebral palsy, receiving enteral nutrition (Cerebral Palsy Enteral Nutrition (CPEN)) via gastrostomy. The first reference group (Cerebral Palsy Controls (CPCs)) consisted of 24 children diagnosed with cerebral palsy and fed orally on a regular diet. The second reference group (Healthy Controls (HCs)) consisted of 24 healthy children with no chronic disease and fed on a regular diet. Isolation and measurement of SCFAs were conducted using gas chromatography. Differences were observed in the median contents of isobutyric acid, valeric acid, and isovaleric acid between the CPC group, which had significantly higher levels of those acids than the HC group. No differences were found between the CPEN and CPC groups nor between the CPEN and HC groups. We conclude that enteral nutrition in cerebral palsy has no influence on the levels of SCFAs.
Full article
(This article belongs to the Special Issue Advances in Fatty Acid Metabolism as the Markers of Civilization Diseases 2.0)
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Open AccessArticle
Integrating Demographics and Imaging Features for Various Stages of Dementia Classification: Feed Forward Neural Network Multi-Class Approach
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Eva Y. W. Cheung, Ricky W. K. Wu, Ellie S. M. Chu and Henry K. F. Mak
Biomedicines 2024, 12(4), 896; https://doi.org/10.3390/biomedicines12040896 - 18 Apr 2024
Abstract
Background: MRI magnetization-prepared rapid acquisition (MPRAGE) is an easily available imaging modality for dementia diagnosis. Previous studies suggested that volumetric analysis plays a crucial role in various stages of dementia classification. In this study, volumetry, radiomics and demographics were integrated as inputs to
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Background: MRI magnetization-prepared rapid acquisition (MPRAGE) is an easily available imaging modality for dementia diagnosis. Previous studies suggested that volumetric analysis plays a crucial role in various stages of dementia classification. In this study, volumetry, radiomics and demographics were integrated as inputs to develop an artificial intelligence model for various stages, including Alzheimer’s disease (AD), mild cognitive decline (MCI) and cognitive normal (CN) dementia classifications. Method: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset was separated into training and testing groups, and the Open Access Series of Imaging Studies (OASIS) dataset was used as the second testing group. The MRI MPRAGE image was reoriented via statistical parametric mapping (SPM12). Freesurfer was employed for brain segmentation, and 45 regional brain volumes were retrieved. The 3D Slicer software was employed for 107 radiomics feature extractions from within the whole brain. Data on patient demographics were collected from the datasets. The feed-forward neural network (FFNN) and the other most common artificial intelligence algorithms, including support vector machine (SVM), ensemble classifier (EC) and decision tree (DT), were used to build the models using various features. Results: The integration of brain regional volumes, radiomics and patient demographics attained the highest overall accuracy at 76.57% and 73.14% in ADNI and OASIS testing, respectively. The subclass accuracies in MCI, AD and CN were 78.29%, 89.71% and 85.14%, respectively, in ADNI testing, as well as 74.86%, 88% and 83.43% in OASIS testing. Balanced sensitivity and specificity were obtained for all subclass classifications in MCI, AD and CN. Conclusion: The FFNN yielded good overall accuracy for MCI, AD and CN categorization, with balanced subclass accuracy, sensitivity and specificity. The proposed FFNN model is simple, and it may support the triage of patients for further confirmation of the diagnosis.
Full article
(This article belongs to the Special Issue State of the Art: Prerequisites, Prevention and Treatment of Neurodegenerative Diseases)
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Open AccessReview
Current Immunotherapy Treatments of Primary Breast Cancer Subtypes
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Savannah R. Brown and Emilie E. Vomhof-DeKrey
Biomedicines 2024, 12(4), 895; https://doi.org/10.3390/biomedicines12040895 - 18 Apr 2024
Abstract
Breast cancer receives the most funding when compared to any other cancer type, according to a global study conducted by The Lancet. Nevertheless, this malignancy remains the most diagnosed cancer among women and relies heavily on a neoadjuvant treatment regimen of chemotherapy
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Breast cancer receives the most funding when compared to any other cancer type, according to a global study conducted by The Lancet. Nevertheless, this malignancy remains the most diagnosed cancer among women and relies heavily on a neoadjuvant treatment regimen of chemotherapy and targeted therapy. After standard treatment, 25–30% of breast cancer patients still develop disease recurrence and must undergo cytoreductive debulking surgery followed by intensive chemotherapy. An array of targeted therapies are currently being utilized and developed to alleviate negative side effects, eradicate cancer growth, and diminish disease recurrence. Immunotherapy is a promising cancer therapy that upregulates one’s immune system to stimulate a therapeutic effect and is utilized for cancer management among other ailments such as immunodeficiencies, hypersensitivity reactions, autoimmune diseases, inflammatory disorders, tissue and organ transplantation, and infectious diseases. This review highlights the five primary subtypes of breast cancer, provides a brief history of immunotherapy, evaluates the current landscape of treating breast cancer with immunotherapy, analyzes selected ongoing or recently completed immunotherapy clinical trials for hormone receptor-positive, HER2-enriched, and triple-negative breast cancer, and examines future trends for the treatment of breast cancer with immunotherapeutic techniques. This review provides a formal summary categorized by breast cancer subtype rather than types of immunotherapeutic treatment.
Full article
(This article belongs to the Special Issue Advanced Research of Oncogene and Therapy Targets in Human Cancers)
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Open AccessReview
The Role of Gut Microbiota and Its Metabolites in Patients with Heart Failure
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Krzysztof Cienkowski, Alicja Cienkowska, Karolina Kupczynska and Agata Bielecka-Dabrowa
Biomedicines 2024, 12(4), 894; https://doi.org/10.3390/biomedicines12040894 - 18 Apr 2024
Abstract
Heart failure (HF) is a significant health concern; early detection and prevention are crucial. Recent studies suggest that the gut microbiota and its metabolites may influence HF development and risk factors. We explored this relationship by examining changes in gut microbiota composition and
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Heart failure (HF) is a significant health concern; early detection and prevention are crucial. Recent studies suggest that the gut microbiota and its metabolites may influence HF development and risk factors. We explored this relationship by examining changes in gut microbiota composition and metabolite levels in HF patients. HF patients often exhibit decreased alpha and beta diversity compared to controls, suggesting lower bacterial richness and community variation. Changes in specific bacterial phyla were observed, with decreases in Firmicutes (e.g., Ruminococcus) and Bacteroidetes (e.g., Prevotella) and increases in Proteobacteria (e.g., Escherichia, Shigella, and Klebsiella) and Actinobacteria. Gut-microbiota-related metabolites have been identified, potentially affecting various body systems, including the cardiovascular system. Among these are short-chain fatty acids (SCFAs), betaine, trimethylamine N-oxide (TMAO), phenylalanine, tryptophan–kynurenine, and phenylacetylgutamine (PAGIn). Although SCFAs positively affect our organisms, patients with HF have been observed to experience a decline in bacteria responsible for producing these chemical compounds. There have been indications of possible links between betaine, TMAO, phenylalanine, tryptophan–kynurenine, PAGIn, and heart failure. TMAO and phenylalanine, in particular, show promise as potential prognostic factors. However, their clinical significance has not yet been thoroughly evaluated and requires further investigation.
Full article
(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)
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Open AccessReview
Trace Amine-Associated Receptors’ Role in Immune System Functions
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Vyacheslav I. Moiseenko, Vera A. Apryatina, Raul R. Gainetdinov and Sergey A. Apryatin
Biomedicines 2024, 12(4), 893; https://doi.org/10.3390/biomedicines12040893 - 18 Apr 2024
Abstract
Trace amines are a separate, independent group of biogenic amines, close in structure to classical monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine that include many products of the endogenous or bacteria-mediated decarboxylation of amino acids. A family of G protein-coupled trace amine-associated
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Trace amines are a separate, independent group of biogenic amines, close in structure to classical monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine that include many products of the endogenous or bacteria-mediated decarboxylation of amino acids. A family of G protein-coupled trace amine-associated receptors (in humans, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) that senses trace amines was discovered relatively recently. They are mostly investigated for their involvement in the olfaction of volatile amines encoding innate behaviors and their potential contribution to the pathogenesis of neuropsychiatric disorders, but the expression of the TAAR family of receptors is also observed in various populations of cells in the immune system. This review is focused on the basic information of the interaction of trace amines and their receptors with cells of the general immune systems of humans and other mammals. We also overview the available data on TAARs’ role in the function of individual populations of myeloid and lymphoid cells. With further research on the regulatory role of the trace amine system in immune functions and on uncovering the contribution of these processes to the pathogenesis of the immune response, a significant advance in the field could be expected. Furthermore, the determination of the molecular mechanisms of TAARs’ involvement in immune system regulation and the further investigation of their potential chemotactic role could bring about the development of new approaches for the treatment of disorders related to immune system dysfunctions.
Full article
(This article belongs to the Section Immunology and Immunotherapy)
Open AccessArticle
Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition
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Amanda Aparecida Ribeiro Andrade, Fernanda Pauli, Carolina Girotto Pressete, Bruno Zavan, João Adolfo Costa Hanemann, Marta Miyazawa, Rafael Fonseca, Ester Siqueira Caixeta, Julia Louise Moreira Nacif, Alexandre Ferro Aissa, Eliezer J. Barreiro and Marisa Ionta
Biomedicines 2024, 12(4), 892; https://doi.org/10.3390/biomedicines12040892 - 18 Apr 2024
Abstract
Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed
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Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.
Full article
(This article belongs to the Special Issue Signaling Pathways That Regulate Cell Proliferation and Apoptosis)
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Open AccessReview
Fibrinaloid Microclots and Atrial Fibrillation
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Douglas B. Kell, Gregory Y. H. Lip and Etheresia Pretorius
Biomedicines 2024, 12(4), 891; https://doi.org/10.3390/biomedicines12040891 - 17 Apr 2024
Abstract
Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We
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Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.
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(This article belongs to the Special Issue Molecular Researches in Pro-thrombotic Disorders)
Open AccessArticle
Associations between Skin Autofluorescence Levels with Cardiovascular Risk and Diabetes Complications in Patients with Type 2 Diabetes
by
Delia Reurean-Pintilei, Anca Pantea Stoian, Teodor Salmen, Roxana-Adriana Stoica, Liliana Mititelu-Tartau, Sandra Lazăr and Bogdan Timar
Biomedicines 2024, 12(4), 890; https://doi.org/10.3390/biomedicines12040890 - 17 Apr 2024
Abstract
Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and
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Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and diabetic complications in T2DM patients. We conducted a single-center, cross-sectional study at Consultmed Hospital in Iasi, Romania, including 885 T2DM patients. The assessment of SAF levels was performed with the AGE Reader™, (Diagnoptics, Groningen, The Netherlands). CVD prevalence was 13.9%, and according to CV risk category distribution, 6.1% fell into the moderate-risk, 1.13% into the high-risk, and 92.77% into the very-high-risk category. The duration of DM averaged 9.0 ± 4.4 years and the mean HbA1c was 7.1% ± 1.3. After adjusting for age and eGFR, HbA1c values showed a correlation with SAF levels in the multivariate regression model, where a 1 SD increase in HbA1c was associated with a 0.105 SD increase in SAF levels (Nagelkerke R2 = 0.110; p < 0.001). For predicting very high risk with an SAF cut-off of 2.35, sensitivity was 67.7% and specificity was 56.2%, with an AUC of 0.634 (95% CI 0.560–0.709, p = 0.001). In T2DM, elevated SAF levels were associated with higher CV risk and HbA1c values, with 2.35 identified as the optimal SAF cut-off for very high CV risk.
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(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications)
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Open AccessArticle
NCI 159456 PERK Inhibitor as a Targeted Therapy for Lung Cancer: An In Vitro Study
by
Wioletta Rozpędek-Kamińska, Grzegorz Galita, Natalia Siwecka, Zuzanna Granek, Julia Barczuk, Kamil Saramowicz and Ireneusz Majsterek
Biomedicines 2024, 12(4), 889; https://doi.org/10.3390/biomedicines12040889 - 17 Apr 2024
Abstract
Non-small cell lung cancer (NSCLC) represents the most common histological type of lung cancer, characterized by a five-year survival rate of 15% and poor prognosis. Accumulating evidence indicates a prominent role of endoplasmic reticulum (ER) stress and the protein kinase RNA-like ER kinase
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Non-small cell lung cancer (NSCLC) represents the most common histological type of lung cancer, characterized by a five-year survival rate of 15% and poor prognosis. Accumulating evidence indicates a prominent role of endoplasmic reticulum (ER) stress and the protein kinase RNA-like ER kinase (PERK)-dependent pathway of the unfolded protein response (UPR) in the pathogenesis of NSCLC. Increased expression of downstream targets of PERK was observed in various subtypes of NSCLC, and it was associated with a more aggressive phenotype, high risk of recurrence, and poor prognosis. Therefore, the present study aimed to investigate the biological effect of the selective PERK inhibitor NCI 159456 on A549 NSCLC cells and Human Pulmonary Fibroblasts (HPF) in vitro. Treatment of both normal and ER-stressed A549 cells with NCI 159456 resulted in a significant increase in the mRNA expression level of pro-apoptotic genes like activating transcription factor 4 (ATF4), DNA damage inducible transcript 3 (DDIT3), and BCL2 Associated X, Apoptosis Regulator (BAX) as well as a decreased level of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2). Cytotoxicity and genotoxicity analyses revealed that NCI 159456 significantly decreased viability and increased DNA damage in A549 cells under normal and ER stress conditions. Caspase-3 and reactive oxygen species (ROS) detection assays demonstrated that NCI 159456 significantly induced apoptosis and increased the ROS level in normal and ER-stressed A549 cells. Importantly, treatment with the inhibitor did not affect substantially normal HPF cells at any used concentration. The results indicate that PERK inhibitors could potentially be applied as a targeted therapy for NSCLC.
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(This article belongs to the Section Cancer Biology and Oncology)
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Open AccessSystematic Review
Circulating microRNAs as Non-Invasive Biomarkers in Endometriosis Diagnosis—A Systematic Review
by
Arne Vanhie, Ellen Caron, Eveline Vermeersch, Dorien O, Carla Tomassetti, Christel Meuleman, Pieter Mestdagh and Thomas M. D’Hooghe
Biomedicines 2024, 12(4), 888; https://doi.org/10.3390/biomedicines12040888 - 17 Apr 2024
Abstract
The aim of this systematic review is to assess the power of circulating miRNAs as biomarkers as a diagnostic tool in endometriosis. In endometriosis-suspected women with uncertain imaging, the only way to confirm or exclude endometriosis with certainty is currently laparoscopy. This creates
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The aim of this systematic review is to assess the power of circulating miRNAs as biomarkers as a diagnostic tool in endometriosis. In endometriosis-suspected women with uncertain imaging, the only way to confirm or exclude endometriosis with certainty is currently laparoscopy. This creates a need for non-invasive diagnostics. We searched the literature through the PubMed database using the Mesh terms ‘endometriosis’ and ‘miRNAs’. Some, but limited, overlap was found between the 32 articles included, with a total of 20 miRNAs reported as dysregulated in endometriosis in two or more studies. MiR-17-5p was reported as dysregulated in six studies, followed by miR-451a and let-7b-5p in four studies and miR-20a-5p, miR-143-3p, miR-199a-5p and miR-3613-5p in three studies. Furthermore, a possible impact of the menstrual phase on miRNA expression was noted in five studies, while no influence of hormonal intake was observed in any included study. The modest reproducibility between studies may be attributable to biological variability as well as to the lack of universal protocols, resulting in pre- and analytical variability. Despite the identification of several suitable candidate biomarkers among the miRNAs, the need for high-quality studies with larger and well-defined population cohorts and the use of standardized protocols lingers.
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(This article belongs to the Special Issue Biomarkers of Endometriosis)
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Validating Brain Tumor Reporting and Data System (BT-RADS) as a Diagnostic Tool for Glioma Follow-Up after Surgery
by
Yassir Edrees Almalki, Mohammad Abd Alkhalik Basha, Maha Ibrahim Metwally, Nesma Adel Zeed, Mohamad Gamal Nada, Sharifa Khalid Alduraibi, Ahmed A. Morsy, Rawda Balata, Ahmed Z. Al Attar, Mona M. Amer, Mohamed Abd El-Aziz Mohamed Farag, Sameh Abdelaziz Aly, Ahmed M. Abdelkhalik Basha and Enas Mahmoud Hamed
Biomedicines 2024, 12(4), 887; https://doi.org/10.3390/biomedicines12040887 - 17 Apr 2024
Abstract
Gliomas are a type of brain tumor that requires accurate monitoring for progression following surgery. The Brain Tumor Reporting and Data System (BT-RADS) has emerged as a potential tool for improving diagnostic accuracy and reducing the need for repeated operations. This prospective multicenter
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Gliomas are a type of brain tumor that requires accurate monitoring for progression following surgery. The Brain Tumor Reporting and Data System (BT-RADS) has emerged as a potential tool for improving diagnostic accuracy and reducing the need for repeated operations. This prospective multicenter study aimed to evaluate the diagnostic accuracy and reliability of BT-RADS in predicting tumor progression (TP) in postoperative glioma patients and evaluate its acceptance in clinical practice. The study enrolled patients with a history of partial or complete resection of high-grade glioma. All patients underwent two consecutive follow-up brain MRI examinations. Five neuroradiologists independently evaluated the MRI examinations using the BT-RADS. The diagnostic accuracy of the BT-RADS for predicting TP was calculated using histopathology after reoperation and clinical and imaging follow-up as reference standards. Reliability based on inter-reader agreement (IRA) was assessed using kappa statistics. Reader acceptance was evaluated using a short survey. The final analysis included 73 patients (male, 67.1%; female, 32.9%; mean age, 43.2 ± 12.9 years; age range, 31–67 years); 47.9% showed TP, and 52.1% showed no TP. According to readers, TP was observed in 25–41.7% of BT-3a, 61.5–88.9% of BT-3b, 75–90.9% of BT-3c, and 91.7–100% of BT-RADS-4. Considering >BT-RADS-3a as a cutoff value for TP, the sensitivity, specificity, and accuracy of the BT-RADS were 68.6–85.7%, 84.2–92.1%, and 78.1–86.3%, respectively, according to the reader. The overall IRA was good (κ = 0.75) for the final BT-RADS classification and very good for detecting new lesions (κ = 0.89). The readers completely agreed with the statement “the application of the BT-RADS should be encouraged” (score = 25). The BT-RADS has good diagnostic accuracy and reliability for predicting TP in postoperative glioma patients. However, BT-RADS 3 needs further improvements to increase its diagnostic accuracy.
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(This article belongs to the Special Issue Establishment of State-of-the-Art Methods/Techniques and Identification of Novel Biomarkers in Brain Tumor Diagnosis)
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Open AccessReview
Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis
by
Emma Bassette and Jennifer A. Ducie
Biomedicines 2024, 12(4), 886; https://doi.org/10.3390/biomedicines12040886 - 17 Apr 2024
Abstract
Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. Type I EC is more common than Type II EC (80% vs. 20%) and is associated with a hyperestrogenic state. Estrogen unopposed by progesterone
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Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. Type I EC is more common than Type II EC (80% vs. 20%) and is associated with a hyperestrogenic state. Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. Studies show that BMI > 30 kg/m2, prolonged duration of menses, nulliparity, presence of polycystic ovarian syndrome, and Lynch syndrome are the most common causes of EC in premenopausal women. Currently, there are no guidelines established to indicate premenopausal patients who should be screened. This review aims to synthesize current data on the etiology, risk factors, presentation, evaluation, and prognosis of endometrial cancer in this population.
Full article
(This article belongs to the Special Issue Endometrial Cancer: From Pathobiology to Treatment)
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