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
Comparative Neurological and Behavioral Assessment of Central and Peripheral Stimulation Technologies for Induced Pain and Cognitive Tasks
Biomedicines 2024, 12(6), 1269; https://doi.org/10.3390/biomedicines12061269 - 6 Jun 2024
Abstract
Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation—tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation—TENS over the median nerve) in pain inhibition during a cognitive task
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Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation—tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation—TENS over the median nerve) in pain inhibition during a cognitive task in healthy volunteers and to observe potential neuro-cognitive improvements. Eighty healthy participants underwent a comprehensive experimental protocol, including cognitive assessments, the Cold Pressor Test (CPT) for pain induction, and tDCS/TENS administration. EEG recordings were conducted pre- and post-intervention across all conditions. The protocol for this study was categorized into four groups: G1 (control), G2 (TENS), G3 (anodal-tDCS), and G4 (cathodal-tDCS). Paired t-tests (p < 0.05) were conducted to compare Pre-Stage, Post-Stage, and neuromodulation conditions, with t-values providing insights into effect magnitudes. The result showed a reduction in pain intensity with TENS (p = 0.002, t-value = −5.34) and cathodal-tDCS (p = 0.023, t-value = −5.08) and increased pain tolerance with TENS (p = 0.009, t-value = 4.98) and cathodal-tDCS (p = 0.001, t-value = 5.78). Anodal-tDCS (p = 0.041, t-value = 4.86) improved cognitive performance. The EEG analysis revealed distinct neural oscillatory patterns across the groups. Specifically, G2 and G4 showed delta-power reductions, while G3 observed an increase. Moreover, G2 exhibited increased theta-power in the occipital region during CPT and Post-Stages. In the alpha-band, G2, G3, and G4 had reductions Post-Stage, while G1 and G3 increased. Additionally, beta-power increased in the frontal region for G2 and G3, contrasting with a reduction in G4. Furthermore, gamma-power globally increased during CPT1, with G1, G2, and G3 showing reductions Post-Stage, while G4 displayed a global decrease. The findings confirm the efficacy of TENS and tDCS as possible non-drug therapeutic alternatives for cognition with alleviation from pain.
Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
Open AccessArticle
Impaired Modulation of the Autonomic Nervous System in Adult Patients with Major Depressive Disorder
by
Elise Böttcher, Lisa Sofie Schreiber, David Wozniak, Erik Scheller, Frank M. Schmidt and Johann Otto Pelz
Biomedicines 2024, 12(6), 1268; https://doi.org/10.3390/biomedicines12061268 - 6 Jun 2024
Abstract
Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate
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Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone.
Full article
(This article belongs to the Special Issue Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets)
Open AccessArticle
Feasibility of Predicting Surgical Duration in Endometriosis Using Numerical Multi-Scoring System of Endometriosis (NMS-E)
by
Masao Ichikawa, Tatsunori Shiraishi, Naofumi Okuda, Shigeru Matsuda, Kimihiko Nakao, Hanako Kaseki, Go Ichikawa, Shigeo Akira, Masafumi Toyoshima, Yoshimitu Kuwabara and Shunji Suzuki
Biomedicines 2024, 12(6), 1267; https://doi.org/10.3390/biomedicines12061267 - 6 Jun 2024
Abstract
Background: Endometriosis is a multifaceted gynecological condition that poses diagnostic challenges and affects a significant number of women worldwide, leading to pain, infertility, and a reduction in patient quality of life (QoL). Traditional diagnostic methods, such as the revised American Society for Reproductive
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Background: Endometriosis is a multifaceted gynecological condition that poses diagnostic challenges and affects a significant number of women worldwide, leading to pain, infertility, and a reduction in patient quality of life (QoL). Traditional diagnostic methods, such as the revised American Society for Reproductive Medicine (r-ASRM) classification, have limitations, particularly in preoperative settings. The Numerical Multi-Scoring System of Endometriosis (NMS-E) has been proposed to address these shortcomings by providing a comprehensive preoperative diagnostic tool that integrates findings from pelvic examinations and transvaginal ultrasonography. Methods: This retrospective study aims to validate the effectiveness of the NMS-E in predicting surgical outcomes and correlating with the severity of endometriosis. Data from 111 patients at Nippon Medical School Hospital were analyzed to determine the correlation between NMS-E scores, including E-score—a severity indicator—traditional scoring systems, surgical duration, blood loss, and clinical symptoms. This study also examined the need to refine parameters for deep endometriosis within the NMS-E to enhance its predictive accuracy for disease severity. Results: The mean age of the patient cohort was 35.1 years, with the majority experiencing symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. A statistically significant positive correlation was observed between the NMS-E’s E-score and the severity of endometriosis, particularly in predicting surgical duration (Spearman correlation coefficient: 0.724, p < 0.01) and blood loss (coefficient: 0.400, p < 0.01). The NMS-E E-score also correlated strongly with the r-ASRM scores (coefficient: 0.758, p < 0.01), exhibiting a slightly more excellent predictive value for surgical duration than the r-ASRM scores alone. Refinements in the methodology for scoring endometriotic nodules in uterine conditions improved the predictive accuracy for surgical duration (coefficient: 0.752, p < 0.01). Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease’s severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.
Full article
(This article belongs to the Special Issue Advances in Endometriosis: Exploring Molecular Mechanisms, Diagnosis, and Treatment)
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Open AccessReview
Management of Fibromyalgia: An Update
by
Eric A. Jones, Farrah Asaad, Nishil Patel, Esha Jain and Alaa Abd-Elsayed
Biomedicines 2024, 12(6), 1266; https://doi.org/10.3390/biomedicines12061266 - 6 Jun 2024
Abstract
Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review,
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Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management—namely duloxetine, milnacipran, pregabalin, and amitriptyline—which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.
Full article
(This article belongs to the Collection Neurogenic Neuroinflammation in Fibromyalgia)
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Open AccessArticle
Correlation of Psychological Factors, Obesity, Serum Cortisol, and C-Reactive Protein in Patients with Fibromyalgia Diagnosed with Obstructive Sleep Apnea and Other Comorbidities
by
Edwin Meresh, Kristine Khieu, Jennifer Krupa, McKinney Bull, Miloni Shah, Safiya Aijazi, Drishti Jain and Jade Bae
Biomedicines 2024, 12(6), 1265; https://doi.org/10.3390/biomedicines12061265 - 6 Jun 2024
Abstract
Background: Fibromyalgia (FM) is a chronic pain disorder and is associated with disability, and high levels of pain and suffering. FM is known to co-occur with obesity and obstructive sleep apnea (OSA). Individuals with FM often experience symptoms of pain, depression and anxiety,
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Background: Fibromyalgia (FM) is a chronic pain disorder and is associated with disability, and high levels of pain and suffering. FM is known to co-occur with obesity and obstructive sleep apnea (OSA). Individuals with FM often experience symptoms of pain, depression and anxiety, sleep disturbances, and fatigue. These symptoms may be exacerbated by OSA and contribute to the symptoms’ severity in FM. Obesity is a common comorbidity in OSA patients, and as FM and OSA are related in some patients, obesity also may contribute to FM symptom severity. For healthcare providers to effectively manage FM patients, a better understanding of the co-occurrence between these FM comorbidities and psychological factors is needed. Methods: This study was approved by IRB and conducted using a retrospective EPIC chart review. To identify FM, the following ICD-9 codes were used: (729.1) and ICD-10 (M79.7) codes. To identify patients with OSA, the following ICD-9 codes were used: (327.23) and ICD-10 (G47.33). Body Mass Index (BMI), the total number of medical diagnoses, and psychiatric conditions were documented for each patient. The prevalence of psychiatric conditions including depression and anxiety was compared between patients with and without obesity (BMI > 30), and patients with fewer than 25 medical diagnoses and those with 25 or more diagnoses. A chart review was conducted to identify patients with fibromyalgia with prior serum cortisol testing within the last ten years. Cortisol levels were compared and patients were divided into six groups: 1. FM without identified psychiatric conditions; 2. FM with psychiatric diagnosis of adjustment disorders and insomnia; 3. FM with psychiatric diagnosis of depressive disorders; 4. FM with psychiatric diagnosis of bipolar disorders; 5. FM with psychiatric diagnosis of mixed anxiety and depression; 6. FM with psychiatric diagnosis of anxiety disorders. Available C-reactive protein (CRP) values were gathered. Results: The total FM and OSA population was N = 331. The mean age of the patient population was 63.49 years old, with 297 being female. The diagnoses mean was 31.79 ± 17.25 and the mean total psychiatric diagnoses was 2.80 ± 1.66. The mean BMI was 36.69 ± 8.86, with obesity present in 77.95% of the patients. A total of 66.99% of patients had comorbid anxiety and depression with 25 or more medical problems vs. 33.01% of patients who had fewer than 25 medical problems (odds ratio = 1.50). Patients with a BMI < 30 (N = 71) had rates of anxiety and depression at 64.79% and a mean total of 2.79 ± 1.66 psychiatric diagnoses, whereas patients with a BMI > 30 (N = 258) had rates of anxiety and depression at 61.63% (odds ratio = 1.28) and a mean total of 2.80 ± 1.66 psychiatric diagnoses. The most common other psychiatric conditions among FM/OSA patients included hypersomnia and substance use disorders. Cortisol data: Available cortisol results: FM n = 64, female: 59, male: 5, mean age: 63, average BMI: 38.8. The averages for serum cortisol alone for groups 1–6, respectively, are 9.06, 5.49, 13.00, 14.17, 12.25, and 16.03 μg/dL. These results indicate a relatively upward cortisol serum value by the addition of several psychiatric conditions, with the most notable being anxiety for patients with FM. CRP values were available for 53 patients with an average CRP of 4.14. Discussion: Higher rates of anxiety and depression were present in FM patients with 25 or more diagnoses. The odds ratios indicate that a patient with 25 or more medical problems was 1.5 times more likely to have anxiety and depression than those with fewer diagnoses. Additionally, those with a BMI > 30 were 1.3 times more likely to have anxiety and depression than those with a normal BMI. Conclusion: addressing psychological factors in FM and OSA is important as high healthcare utilization is common in patients with FM and OSA.
Full article
(This article belongs to the Special Issue Advanced Research on Fibromyalgia (2nd Edition))
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Navigating Complex Challenges: Preoperative Assessment and Surgical Strategies for Liver Resection in Patients with Fibrosis or Cirrhosis
by
Jennifer A. Kalil, Marc Deschenes, Hugo Perrier, Oran Zlotnik and Peter Metrakos
Biomedicines 2024, 12(6), 1264; https://doi.org/10.3390/biomedicines12061264 - 6 Jun 2024
Abstract
This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative
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This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes.
Full article
(This article belongs to the Special Issue New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma)
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Open AccessReview
TAARs as Novel Therapeutic Targets for the Treatment of Depression: A Narrative Review of the Interconnection with Monoamines and Adult Neurogenesis
by
Taisiia S. Shemiakova, Evgeniya V. Efimova and Raul R. Gainetdinov
Biomedicines 2024, 12(6), 1263; https://doi.org/10.3390/biomedicines12061263 - 6 Jun 2024
Abstract
Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent
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Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent task. In this review, we discuss the current available evidence indicating that G protein-coupled trace amine-associated receptors (TAARs) might represent new targets for depression treatment. The most frequently studied receptor TAAR1 has already been investigated in the treatment of schizophrenia, demonstrating antidepressant and anxiolytic properties. In fact, the TAAR1 agonist Ulotaront is currently undergoing phase 2/3 clinical trials testing its safety and efficacy in the treatment of major depressive disorder and generalized anxiety disorder. Other members of the TAAR family (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) are not only involved in the innate olfaction of volatile amines, but are also expressed in the limbic brain areas. Furthermore, animal studies have shown that TAAR2 and TAAR5 regulate emotional behaviors and thus may hold promise as potential antidepressant targets. Of particular interest is their connection with the dopamine and serotonin systems of the brain and their involvement in the regulation of adult neurogenesis, known to be affected by the antidepressant drugs currently in use. Further non-clinical and clinical studies are necessary to validate TAAR1 (and potentially other TAARs) as novel therapeutic targets for the treatment of depression.
Full article
(This article belongs to the Special Issue Dualistic Equilibrium in Neurotransmission and Beyond: Unraveling the Pathophysiology and Unlocking Novel Therapeutic Targets in Neuropsychiatric Disorders)
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Open AccessReview
Obesity, Metabolic Syndrome, and Osteoarthritis Require Integrative Understanding and Management
by
Veronica Mocanu, Daniel Vasile Timofte, Camelia-Mihaela Zară-Dănceanu and Luminita Labusca
Biomedicines 2024, 12(6), 1262; https://doi.org/10.3390/biomedicines12061262 - 6 Jun 2024
Abstract
Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and
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Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and immune dysregulation in OA pathogenesis, emphasizing the roles of obesity, dyslipidemia, and insulin resistance in altering joint homeostasis. Recent studies have increasingly focused on the complex role of white adipose tissue (WAT) in OA. WAT not only serves metabolic functions but also plays a critical role in systemic inflammation through the release of various adipokines. These adipokines, including leptin and adiponectin, have been implicated in exacerbating cartilage erosion and promoting inflammatory pathways within joint tissues. The overlapping global crises of obesity and metabolic syndrome have significantly impacted joint health. Obesity, now understood to contribute to mechanical joint overload and metabolic dysregulation, heightens the risk of developing OA, particularly in the knee. Metabolic syndrome compounds these risks by inducing chronic inflammation and altering macrophage activity within the joints. The multifaceted effects of obesity and metabolic syndrome extend beyond simple joint loading. These conditions disrupt normal joint function by modifying tissue composition, promoting inflammatory macrophage polarization, and impairing chondrocyte metabolism. These changes contribute to OA progression, highlighting the need for targeted therapeutic strategies that address both the mechanical and biochemical aspects of the disease. Recent advances in understanding the molecular pathways involved in OA suggest potential therapeutic targets. Interventions that modulate macrophage polarization, improve chondrocyte function, or normalize adipokine levels could serve as preventative or disease-modifying therapies. Exploring the role of diet, exercise, and pharmacological interventions in modulating these pathways offers promising avenues for reducing the burden of OA. Furthermore, such methods could prove cost-effective, avoiding the increase in access to healthcare.
Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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DNA Methylation Demonstrates Bronchoalveolar Cell Senescence in People Living with HIV: An Observational Cohort Study
by
Ana I. Hernandez Cordero, Xuan Li, Julia Yang, Chen Xi Yang, Tawimas Shaipanich, Julie L. MacIsaac, Kristy Dever, Michael S. Kobor, Julio Montaner, Marianne Harris, Silvia Guillemi, Shu Fan Paul Man, Don D. Sin and Janice M. Leung
Biomedicines 2024, 12(6), 1261; https://doi.org/10.3390/biomedicines12061261 - 6 Jun 2024
Abstract
Background: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging. Methods: BAL cell DNA methylation from
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Background: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging. Methods: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10). Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV. Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Evaluation of PAGE-B Score for Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients: Reliability, Validity, and Responsiveness
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Evanthia Tourkochristou, Maria Kalafateli, Christos Triantos and Ioanna Aggeletopoulou
Biomedicines 2024, 12(6), 1260; https://doi.org/10.3390/biomedicines12061260 - 5 Jun 2024
Abstract
Abstract: Chronic hepatitis B (CHB) constitutes a major global public health issue, affecting millions of individuals. Despite the implementation of robust vaccination programs, the hepatitis B virus (HBV) significantly influences morbidity and mortality rates. CHB emerges as one of the leading causes of
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Abstract: Chronic hepatitis B (CHB) constitutes a major global public health issue, affecting millions of individuals. Despite the implementation of robust vaccination programs, the hepatitis B virus (HBV) significantly influences morbidity and mortality rates. CHB emerges as one of the leading causes of hepatocellular carcinoma (HCC), introducing a major challenge in the effective management of CHB patients. Therefore, it is of utmost clinical importance to diligently monitor individuals with CHB who are at high risk of HCC development. While various prognostic scores have been developed for surveillance and screening purposes, their accuracy in predicting HCC risk may be limited, particularly in patients under treatment with nucleos(t)ide analogues. The PAGE-B model, incorporating age, gender, and platelet count, has exhibited remarkable accuracy, validity, and reliability in predicting HCC occurrence among CHB patients receiving HBV treatment. Its predictive performance stands out, whether considered independently or in comparison to alternative HCC risk scoring systems. Furthermore, the introduction of targeted adjustments to the calculation of the PAGE-B score might have the potential to further improve its predictive accuracy. This review aims to evaluate the efficacy of the PAGE-B score as a dependable tool for accurate prediction of the development of HCC in CHB patients. The evidence discussed aims to provide valuable insights for guiding recommendations on HCC surveillance within this specific population.
Full article
(This article belongs to the Special Issue Pathological Biomarkers in Precision Medicine)
Open AccessArticle
Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) for Patients—3-Year Follow-Up of Patients with Chronic Kidney Disease
by
Rumen Filev, Mila Lyubomirova, Boris Bogov, Krassimir Kalinov, Julieta Hristova, Dobrin Svinarov, Alexander Garev and Lionel Rostaing
Biomedicines 2024, 12(6), 1259; https://doi.org/10.3390/biomedicines12061259 - 5 Jun 2024
Abstract
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection.
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Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. Data were collected from both CKD and non-CKD patients who survived SARS-CoV-2 infection and were followed for three years as part of a research study on the impact, prognosis, and consequences of COVID-19 infection in CKD patients. In this prospective cohort study, we analyzed clinical records, laboratory findings, and patient-reported outcomes assessed at intervals during follow-up. The results indicated no permanent changes in renal function in any of the groups analyzed, although patients without CKD exhibited faster recovery over time. Furthermore, we examined the effect of RAAS-blocker therapy over time, finding no influence on PASC symptoms or renal function recovery. Regarding PASC symptoms, most patients recovered within a short period, but some required prolonged follow-up and specialized post-recovery management. Following up with patients in the post-COVID-19 period is crucial, as there is still insufficient information and evidence regarding the long-term effects, particularly in relation to CKD.
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(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
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Induction Therapies Determine the Distribution of Perforin and Granzyme B Transcripts in Kidney Transplant Recipients
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Dino Pipic, Marianne Rasmussen, Qais W. Saleh and Martin Tepel
Biomedicines 2024, 12(6), 1258; https://doi.org/10.3390/biomedicines12061258 - 5 Jun 2024
Abstract
Peripheral blood mononuclear cells contain secretory granules with Perforin and Granzyme B for defense against pathogens. The objective of the present study was to compare the effects of immunosuppressive induction therapies on Perforin and Granzyme B transcripts in kidney transplant recipients. Transcripts were
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Peripheral blood mononuclear cells contain secretory granules with Perforin and Granzyme B for defense against pathogens. The objective of the present study was to compare the effects of immunosuppressive induction therapies on Perforin and Granzyme B transcripts in kidney transplant recipients. Transcripts were determined in 408 incident kidney transplant recipients eight days posttransplant using quantitative real-time PCR. Compared to 90 healthy subjects, the median Perforin transcripts were lower in kidney transplant recipients with blood-group ABO-incompatible donors (N = 52), compatible living donors (N = 130), and deceased donors (N = 226) (25.7%; IQR, 6.5% to 46.0%; 31.5%; IQR, 10.9% to 57.7%; and 35.6%; IQR, 20.6% to 60.2%; respectively; p = 0.015 by the Kruskal–Wallis test). Kidney transplant recipients who were treated with thymoglobulin (N = 64) had significantly lower Perforin as well as Granzyme B compared to all other induction therapies (N = 344) (each p < 0.001). Receiver operator characteristics analysis showed that both Perforin (area under curve, 0.919) and Granzyme B (area under curve, 0.915) indicated thyroglobulin-containing induction therapies. Regression analysis showed that both reduction in plasma creatinine and human leukocyte antigen mismatches were positively associated with elevated Perforin/Granzyme B transcript ratio posttransplant. We conclude clinical parameters and therapies affect Perforin and Granzyme B transcripts posttransplant.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessArticle
Zinc Iodide Dimethyl Sulfoxide Reduces Collagen Deposition by Increased Matrix Metalloproteinase-2 Expression and Activity in Lung Fibroblasts
by
Michael Roth, Bo Han, Chong Teck S’ng, Ba Xuan Hoang and Christopher Lambers
Biomedicines 2024, 12(6), 1257; https://doi.org/10.3390/biomedicines12061257 - 5 Jun 2024
Abstract
Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed
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Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor β1 (TGF-β1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-β1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-β1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.
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(This article belongs to the Section Drug Discovery, Development and Delivery)
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Inflammation in the Peripheral Nervous System after Injury
by
Dandan Gu, Yiming Xia, Zihan Ding, Jiaxi Qian, Xi Gu, Huiyuan Bai, Maorong Jiang and Dengbing Yao
Biomedicines 2024, 12(6), 1256; https://doi.org/10.3390/biomedicines12061256 - 5 Jun 2024
Abstract
Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the
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Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways. Previously, inflammation was thought to be detrimental to the body, but further research has shown that appropriate inflammation promotes nerve regeneration, axon regeneration, and myelin formation. On the contrary, excessive inflammation can cause nerve tissue damage and pathological changes, and even lead to neurological diseases. Therefore, after nerve injury, various cells in the body interact with cytokines and chemokines to promote peripheral nerve repair and regeneration by inhibiting the negative effects of inflammation and harnessing the positive effects of inflammation in specific ways and at specific times. Understanding the interaction between neuroinflammation and nerve regeneration provides several therapeutic ideas to improve the inflammatory microenvironment and promote nerve regeneration.
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(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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Association of Vitamin D with Perfluorinated Alkyl Acids in Women with and without Non-Obese Polycystic Ovary Syndrome
by
Alexandra E. Butler, Thozhukat Sathyapalan, Priya Das, Edwina Brennan and Stephen L. Atkin
Biomedicines 2024, 12(6), 1255; https://doi.org/10.3390/biomedicines12061255 - 5 Jun 2024
Abstract
Background. Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency. Methods. Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women (n =
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Background. Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency. Methods. Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women (n = 30) were recruited. Paired serum samples were analyzed for PFAAs (n = 13) using high-performance liquid chromatography–tandem mass spectrometry. Tandem mass spectrometry determined levels of 25(OH)D3 and the active 1,25(OH)2D3. Results. Women with and without PCOS did not differ in age, weight, insulin resistance, or systemic inflammation (C-reactive protein did not differ), but the free androgen index was increased. Four PFAAs were detected in all serum samples: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Serum PFOS was higher in PCOS versus controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05). Linear regression modeling showed that elevated PFHxS had higher odds of a lower 25(OH)D3 (OR: 2.919, 95% CI 0.82–5.75, p = 0.04). Vitamin D did not differ between cohorts and did not correlate with any PFAAs, either alone or when the groups were combined. When vitamin D was stratified into sufficiency (>20 ng/mL) and deficiency (<20 ng/mL), no correlation with any PFAAs was seen. Conclusions. While the analyses and findings here are exploratory in light of relatively small recruitment numbers, when age, BMI, and insulin resistance are accounted for, the PFAAs do not appear to be related to 25(OH)D3 or the active 1,25(OH)2D3 in this Caucasian population, nor do they appear to be associated with vitamin D deficiency, suggesting that future studies must account for these factors in the analysis.
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(This article belongs to the Special Issue Vitamin D in Health and Disease (3rd Edition))
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Recent Advances in the Discovery of Novel Drugs on Natural Molecules
by
Laura Quintieri, Leonardo Caputo and Orazio Nicolotti
Biomedicines 2024, 12(6), 1254; https://doi.org/10.3390/biomedicines12061254 - 5 Jun 2024
Abstract
Natural products (NPs) are always a promising source of novel drugs for tackling unsolved diseases [...]
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(This article belongs to the Special Issue Recent Advances in the Discovery of Novel Drugs on Natural Molecules)
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SIMOA Diagnostics on Alzheimer’s Disease and Frontotemporal Dementia
by
Athanasia Chatziefstathiou, Sezgi Canaslan, Eirini Kanata, Kostas Vekrellis, Vasilios C. Constantinides, George P. Paraskevas, Elisabeth Kapaki, Matthias Schmitz, Inga Zerr, Konstantinos Xanthopoulos, Theodoros Sklaviadis and Dimitra Dafou
Biomedicines 2024, 12(6), 1253; https://doi.org/10.3390/biomedicines12061253 - 4 Jun 2024
Abstract
Background: Accurate diagnosis of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60
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Background: Accurate diagnosis of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic–clinical characteristics. Methods: 136 subjects (AD: n = 43, FTD: n = 33, Controls: n = 60) participated. Single-molecule array (SIMOA), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), TAU, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in CSF were analyzed with a multiplex neuro 4plex kit. Receiver operating characteristic (ROC) curve analysis compared area under the curve (AUC), while the principal of the sparse partial least squares discriminant analysis (sPLS-DA) was used with the intent to strengthen the identification of confident disease clusters. Results: CSF exhibited increased levels of all SIMOA biomarkers in AD compared to Controls (AUCs: 0.71, 0.86, 0.92, and 0.94, respectively). Similar patterns were observed in FTD with NfL, TAU, and UCH-L1 (AUCs: 0.85, 0.72, and 0.91). sPLS-DA revealed two components explaining 19% and 9% of dataset variation. Conclusions: CSF data provide high diagnostic accuracy among AD, FTD, and Control discrimination. Subgroups of demographic–clinical characteristics and biomarker concentration highlighted the potential of combining different kinds of data for successful and more efficient cohort clustering.
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(This article belongs to the Special Issue Advanced Research in Proteinopathies)
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Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders
by
Sadik Bay, Chander S. Digwal, Ananda M. Rodilla Martín, Sahil Sharma, Aleksandra Stanisavljevic, Anna Rodina, Anoosha Attaran, Tanaya Roychowdhury, Kamya Parikh, Eugene Toth, Palak Panchal, Eric Rosiek, Chiranjeevi Pasala, Ottavio Arancio, Paul E. Fraser, Melissa J. Alldred, Marco A. M. Prado, Stephen D. Ginsberg and Gabriela Chiosis
Biomedicines 2024, 12(6), 1252; https://doi.org/10.3390/biomedicines12061252 - 4 Jun 2024
Abstract
Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce
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Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology.
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(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases)
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Formation of Multinucleated Giant Cells after Experimental Intracerebral Hemorrhage: Characteristics and Role of Complement C3
by
Xiongjie Fu, Ming Wang, Yingfeng Wan, Ya Hua, Richard F. Keep and Guohua Xi
Biomedicines 2024, 12(6), 1251; https://doi.org/10.3390/biomedicines12061251 - 4 Jun 2024
Abstract
Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear.
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Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 μL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution.
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(This article belongs to the Special Issue Cerebral Hemorrhages: From Pathophysiologic Mechanisms to Therapeutic Strategies)
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Does Metabolic Syndrome and Its Components Have Prognostic Significance for Renal and Cardiovascular Outcomes in IgA Nephropathy?
by
Balázs Sági, Tibor Vas, Botond Csiky, Judit Nagy and Tibor József Kovács
Biomedicines 2024, 12(6), 1250; https://doi.org/10.3390/biomedicines12061250 - 4 Jun 2024
Abstract
Background: Patients with IgA nephropathy (IgAN), a chronic kidney disease (CKD), are significantly more likely to have cardiovascular (CV) mortality and morbidity than the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease
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Background: Patients with IgA nephropathy (IgAN), a chronic kidney disease (CKD), are significantly more likely to have cardiovascular (CV) mortality and morbidity than the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The purpose of this study was to determine how metabolic characteristics in a homogeneous population of CKD patients relate to prognosis. Methods: A total of 145 patients with CKD stages 1–4 diagnosed with IgA nephropathy (92 men and 53 women, aged 54.7 ± 13 years) were examined and monitored for a median of 190 months. All-cause mortality and any CV event, such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal), have been included in the composite endpoints (CV and renal). Results: Patients with MetS had significantly more primary endpoint events (23/65 patients vs. 15/60 patients, p < 0.001) compared to the non-MetS group. The MetS group had a statistically significant increase in both primary renal and CV endpoints (18/65 vs. 10/60, p = 0.001), and in CV endpoint events (7/65 vs. 6/60, p = 0.029) among the secondary endpoints (CV and renal separately). Based on Cox regression analysis, the main endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus. Independent predictors of secondary renal endpoints were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. When Kaplan–Meier curves were analyzed at the combined endpoints (CV and renal) or each endpoint independently, significant differences were seen between MetS and non-MetS. With more MetS components, the primary endpoint rate increased significantly (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusions: Our results show that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.
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(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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