-
‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA
-
Optimizing TMS Coil Placement Approaches for Targeting the Dorsolateral Prefrontal Cortex in Depressed Adolescents: An Electric Field Modeling Study
-
Current Advances in Mitochondrial Targeted Interventions in Alzheimer’s Disease
-
Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Cyp2c70−/− Mice with a Human-like Bile Acid Composition
-
Optimization of Nutrition after Brain Injury: Mechanistic and Therapeutic Considerations
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 14.7 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first 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
Bridging Retinal and Cerebral Neurodegeneration: A Focus on Crosslinks between Alzheimer–Perusini’s Disease and Retinal Dystrophies
Biomedicines 2023, 11(12), 3258; https://doi.org/10.3390/biomedicines11123258 (registering DOI) - 08 Dec 2023
Abstract
In the early stages of Alzheimer–Perusini’s disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast sensitivity, and visual acuity problems. As the disease progresses, there is a connection with glaucoma and age-related macular degeneration (AMD) leading to retinal
[...] Read more.
In the early stages of Alzheimer–Perusini’s disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast sensitivity, and visual acuity problems. As the disease progresses, there is a connection with glaucoma and age-related macular degeneration (AMD) leading to retinal cell death. The retina’s involvement suggests a link with the hippocampus, where most AD forms start. A thinning of the retinal nerve fiber layer (RNFL) due to the loss of retinal ganglion cells (RGCs) is seen as a potential AD diagnostic marker using electroretinography (ERG) and optical coherence tomography (OCT). Amyloid beta fragments (Aβ), found in the eye’s vitreous and aqueous humor, are also present in the cerebrospinal fluid (CSF) and accumulate in the retina. Aβ is known to cause tau hyperphosphorylation, leading to its buildup in various retinal layers. However, diseases like AD are now seen as mixed proteinopathies, with deposits of the prion protein (PrP) and α-synuclein found in affected brains and retinas. Glial cells, especially microglial cells, play a crucial role in these diseases, maintaining immunoproteostasis. Studies have shown similarities between retinal and brain microglia in terms of transcription factor expression and morphotypes. All these findings constitute a good start to achieving better comprehension of neurodegeneration in both the eye and the brain. New insights will be able to bring the scientific community closer to specific disease-modifying therapies.
Full article
(This article belongs to the Special Issue State of the Art: Prerequisites, Prevention and Treatment of Neurodegenerative Diseases)
Open AccessArticle
Role of Telomere Length in Survival of Patients with Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases
by
, , , , , , , , , , and
Biomedicines 2023, 11(12), 3257; https://doi.org/10.3390/biomedicines11123257 (registering DOI) - 08 Dec 2023
Abstract
Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, with idiopathic pulmonary fibrosis (IPF) being one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as
[...] Read more.
Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, with idiopathic pulmonary fibrosis (IPF) being one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as a prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan–Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatic disease (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients. Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.
Full article
(This article belongs to the Special Issue The Role of Telomere and Telomerase in Human Disease)
Open AccessReview
The Impact of Obesity on Inflammatory Bowel Disease
Biomedicines 2023, 11(12), 3256; https://doi.org/10.3390/biomedicines11123256 (registering DOI) - 08 Dec 2023
Abstract
Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available
[...] Read more.
Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available studies are conflicting. It does, however, appear to negatively influence disease course whilst impacting on our medical and surgical therapies. The pro-inflammatory profile of the visceral adipose tissue might play a role in the pathogenesis and course of Crohn’s Disease (CD). Interestingly, isolating the mesentery from the surgical anastomosis using a KONO-S technique significantly decreases anastomotic recurrence rate. Anti-obesity therapy is not widely used in IBD but was suggested as an adjunctive therapy in those patients. In this review, we aimed to highlight the epidemiology of obesity in IBD and to describe its influence on disease course and outcomes.
Full article
(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches)
►▼
Show Figures

Figure 1
Open AccessArticle
Vagal Stimulation Ameliorates Non-Alcoholic Fatty Liver Disease in Rats
by
, , , , , , , and
Biomedicines 2023, 11(12), 3255; https://doi.org/10.3390/biomedicines11123255 (registering DOI) - 08 Dec 2023
Abstract
Background: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation
[...] Read more.
Background: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS). Aim of the study: To investigate the possible preventive impacts of VNS against adult rats’ NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms. Methods: A total of thirty-two adult male rats were split into two groups: the HFD-induced NAFLD group (n = 24) and the control normal group (n = 8). The obesogenic diet was maintained for 12 weeks to induce hepatic steatosis. The HFD-induced NAFLD group (n = 24) was separated into three groups: the group without treatment (n = 8), the group with sham stimulation (n = 8), and the group with VNS treatment (n = 8). VNS was delivered for 30 min per day for 6 weeks after the establishment of NAFLD using a digital TENS device. The subsequent assessments included hepatic triglyceride, cholesterol content, serum lipid profile, and liver function testing. In this context, inflammatory biomarkers (TNF-α, IL-6) and hepatic oxidative stress (MDA, SOD, and GPx) were also assessed. To clarify the possible mechanisms behind the protective benefits of VNS, additional histological inspection and immunohistochemistry analysis of TNF-α and Caspase-3 were performed. Results: In the NAFLD-affected obese rats, VNS markedly decreased the rats’ body mass index (BMI) and abdominal circumference (AC). Liver function markers (albumin, ALT, and AST) and the serum lipid profile—which included a notable decrease in the amounts of hepatic triglycerides and cholesterol—were both markedly improved. Additionally, oxidative stress and inflammatory indicators showed a considerable decline with VNS. Notably, the liver tissues examined by histopathologists revealed that there is evidence of the protective impact of VNS on the oxidative and inflammatory states linked to HFD-induced NAFLD while maintaining the architectural and functional condition of the liver. Conclusions: Our findings suggest that VNS may represent a promising therapeutic candidate for managing NAFLD induced by obesity. It can be considered to be an effective adjuvant physiological intervention for the obese population with NAFLD to spare the liver against obesity-induced deleterious injury.
Full article
(This article belongs to the Special Issue Signaling Pathways That Regulate Cell Proliferation and Apoptosis)
►▼
Show Figures

Figure 1
Open AccessArticle
The Preserflo MicroShunt Affects Microvascular Flow Density in Optical Coherence Tomography Angiography
by
, , , , , , , and
Biomedicines 2023, 11(12), 3254; https://doi.org/10.3390/biomedicines11123254 - 08 Dec 2023
Abstract
Intraocular pressure (IOP) lowering surgery has been shown to alter microvascular density in glaucoma patients. The aim of this study is to report changes in retinal flow density (FD) over the course of treatment with the Preserflo MicroShunt, using optical coherence tomography angiography
[...] Read more.
Intraocular pressure (IOP) lowering surgery has been shown to alter microvascular density in glaucoma patients. The aim of this study is to report changes in retinal flow density (FD) over the course of treatment with the Preserflo MicroShunt, using optical coherence tomography angiography (OCTA). 34 eyes from 34 patients who underwent Preserflo MicroShunt implantation were prospectively enrolled in this study. OCTA imaging was conducted at the superficial (SCP), deep (DCP) and radial peripapillary plexus (RPC) levels. The progression of FD and IOP was assessed at different time points from baseline to six months postoperatively for the entire patient population, as well as disease severity subgroups. The Preserflo MicroShunt achieved a significant reduction in IOP over the course of six months (median: 8 mmHg; p < 0.01). FD values of the SCP and DCP did not show significant fluctuations, even after adjusting for disease severity. FD of the RPC decreased significantly over the course of six months postoperatively from 42.31 at baseline to 39.59 at six months postoperatively (p < 0.01). The decrease in peripapillary FD was strongest in patients with advanced glaucoma (median: −3.58). These observations hint towards dysfunctional autoregulatory mechanisms in capillaries surrounding the optic nerve head in advanced glaucoma. In comparison, the microvascular structure of the macula appeared more resilient to changes in IOP.
Full article
(This article belongs to the Special Issue Glaucoma: New Diagnostic and Therapeutic Approaches)
►▼
Show Figures

Figure 1
Open AccessArticle
The Intraoperative Administration of Dexmedetomidine Alleviates Postoperative Inflammatory Response in Patients Undergoing Laparoscopy-Assisted Gastrectomy: A Double-Blind Randomized Controlled Trial
by
, , , , , , and
Biomedicines 2023, 11(12), 3253; https://doi.org/10.3390/biomedicines11123253 - 08 Dec 2023
Abstract
Surgical stress can compromise the immune system of patients with cancer, affecting susceptibility to perioperative infections, tumor progression, treatment responses, and postoperative recovery. Perioperatively reducing inflammatory responses could improve outcomes. We determined the impact of intraoperative dexmedetomidine administration on the inflammatory response and
[...] Read more.
Surgical stress can compromise the immune system of patients with cancer, affecting susceptibility to perioperative infections, tumor progression, treatment responses, and postoperative recovery. Perioperatively reducing inflammatory responses could improve outcomes. We determined the impact of intraoperative dexmedetomidine administration on the inflammatory response and postoperative recovery in patients undergoing elective laparoscopy-assisted gastrectomy. These patients were randomly assigned to the dexmedetomidine or control group (n = 42 each). The primary endpoint was the C-reactive protein (CRP) level on postoperative day 1. The secondary endpoints included the perioperative interleukin (IL)-6 levels, postoperative numerical rating scale (NRS) scores, and rescue analgesic doses. There were no significant between-group differences in terms of CRP levels. The IL-6 levels at the end of the surgery, NRS scores in the post-anesthesia care unit, and rescue pethidine requirements within the first hour postoperatively were significantly lower in the dexmedetomidine group than in the control group. The bolus deliveries-to-attempts ratio (via patient-controlled analgesia) at 2 h differed significantly between the two groups. However, IL-6 reduction was confined to a single timepoint, and the postoperative analgesic effects lasted for the first 2 h postoperatively. Low-dose dexmedetomidine infusion (0.4 µg kg−1 h−1) during laparoscopy-assisted gastrectomy exerts minimal anti-inflammatory effects.
Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment)
►▼
Show Figures

Figure 1
Open AccessReview
The Impact of Maternal Obesity on Adipose Progenitor Cells
Biomedicines 2023, 11(12), 3252; https://doi.org/10.3390/biomedicines11123252 - 08 Dec 2023
Abstract
The concept of Developmental Origin of Health and Disease (DOHaD) postulates that adult-onset metabolic disorders may originate from suboptimal conditions during critical embryonic and fetal programming windows. In particular, nutritional disturbance during key developmental stages may program the set point of adiposity and
[...] Read more.
The concept of Developmental Origin of Health and Disease (DOHaD) postulates that adult-onset metabolic disorders may originate from suboptimal conditions during critical embryonic and fetal programming windows. In particular, nutritional disturbance during key developmental stages may program the set point of adiposity and its associated metabolic diseases later in life. Numerous studies in mammals have reported that maternal obesity and the resulting accelerated growth in neonates may affect adipocyte development, resulting in persistent alterations in adipose tissue plasticity (i.e., adipocyte proliferation and storage) and adipocyte function (i.e., insulin resistance, impaired adipokine secretion, reduced thermogenesis, and higher inflammation) in a sex- and depot-specific manner. Over recent years, adipose progenitor cells (APCs) have been shown to play a crucial role in adipose tissue plasticity, essential for its development, maintenance, and expansion. In this review, we aim to provide insights into the developmental timeline of lineage commitment and differentiation of APCs and their role in predisposing individuals to obesity and metabolic diseases. We present data supporting the possible implication of dysregulated APCs and aberrant perinatal adipogenesis through epigenetic mechanisms as a primary mechanism responsible for long-lasting adipose tissue dysfunction in offspring born to obese mothers.
Full article
(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)
►▼
Show Figures

Figure 1
Open AccessArticle
Histone H3 Acetylation Is Involved in Retinoid Acid-Induced Neural Differentiation through Increasing Mitochondrial Function
Biomedicines 2023, 11(12), 3251; https://doi.org/10.3390/biomedicines11123251 - 08 Dec 2023
Abstract
Histone acetylation and mitochondrial function contribute importantly to neural differentiation, which is critically associated with neurodevelopmental disorders such as Down Syndrome (DS). However, whether and how histone acetylation regulates mitochondrial function and further affects neural differentiation has not been well described. In this
[...] Read more.
Histone acetylation and mitochondrial function contribute importantly to neural differentiation, which is critically associated with neurodevelopmental disorders such as Down Syndrome (DS). However, whether and how histone acetylation regulates mitochondrial function and further affects neural differentiation has not been well described. In this study, when treated with retinoid acid (RA), the human neuroblastoma SH-SY5Y cell line was used as a neural differentiation model. We found that the acetylation of histone H3, especially H3 lysine 14 acetylation (H3K14ac), and mitochondrial function, including biogenesis and electron transport chain, were enhanced during neural differentiation. Specific inhibition of histone acetyltransferases (HATs) induced neural differentiation deficits, accompanied by downregulation of mitochondrial function. Furthermore, RA receptors (RARs) interacting with HATs were involved in the increased H3K14ac and the enhanced mitochondrial function during the neural differentiation process. Finally, receptor-interacting protein 140 (RIP140), a co-repressor of RARs, was also involved in regulating histone acetylation. RIP140 overexpression inhibited histone acetylation and mediated negative feedback on target genes which are involved in RA signaling. These findings evidenced that when interacting with RARs which had been negatively regulated by RIP140, RA promoted neural differentiation by promoting H3K14ac and enhanced mitochondrial function. This provides a molecular foundation for further investigations into abnormal neural development.
Full article
(This article belongs to the Section Neurobiology and Neurologic Disease)
►▼
Show Figures

Figure 1
Open AccessArticle
Modification of Peripheral Blood Flow and Angiogenesis by CO2 Water-Bath Therapy in Diabetic Skeletal Muscle with or without Ischemia
Biomedicines 2023, 11(12), 3250; https://doi.org/10.3390/biomedicines11123250 - 08 Dec 2023
Abstract
Previously, it was shown that both blood flow and angiogenesis in the ischemic hind limb of diabetic rats were increased upon CO2 treatment for 4 weeks. In the present study, we have compared the effects of 6 weeks CO2 therapy in
[...] Read more.
Previously, it was shown that both blood flow and angiogenesis in the ischemic hind limb of diabetic rats were increased upon CO2 treatment for 4 weeks. In the present study, we have compared the effects of 6 weeks CO2 therapy in diabetic rats with or without peripheral ischemia. Diabetes was induced in rats by a tail vein injection of streptozotocin (65 mg/kg body weight), whereas peripheral ischemia was produced by occluding the femoral artery at 2 weeks of inducing diabetes. Both diabetic and diabetic-ischemic animals were treated with or without CO2 water-bath at 37 °C for 6 weeks (30 min/day; 5 days/week) starting at 2 weeks, after the induction of ischemia. CO2 treatment did not affect heart rate and R-R interval as well as plasma levels of creatine kinase, glucose, cholesterol, triglycerides and high density lipoproteins. Unlike the levels of plasma Ox-LDL, MDA and TNF-α, the levels of NO in diabetic group were increased by CO2 water-bath treatment. On the other hand, the levels of plasma Ox-LDL and MDA were decreased whereas that of NO was increased without any changes in TNF-α level in diabetic-ischemic animals upon CO2 therapy. Treatment of diabetic animals with CO2 increased peak, mean and minimal blood flow by 20, 49 and 43% whereas these values were increased by 53, 26 and 80% in the diabetic-ischemic group by CO2 therapy, respectively. Blood vessel count in diabetic and diabetic-ischemic skeletal muscles was increased by 73 and 136% by CO2 therapy, respectively. These data indicate that peripheral ischemia augmented the increase in blood flow and development of angiogenesis in diabetic skeletal muscle upon CO2 therapy. It is suggested that greater beneficial effects of CO2 therapy in diabetic-ischemic animals in comparison to diabetic group may be a consequence of difference of changes in the redox-sensitive signal transduction mechanisms.
Full article
(This article belongs to the Special Issue Peripheral Artery Disease and Diabetic Foot Ulcer: From Bench to Clinic)
►▼
Show Figures

Figure 1
Open AccessArticle
Antinociceptive Effect of the Combination of a Novel α4β2* Agonist with Donepezil in a Chronic Pain Model
by
, , , , , , , and
Biomedicines 2023, 11(12), 3249; https://doi.org/10.3390/biomedicines11123249 - 08 Dec 2023
Abstract
Chronic pain presents a major challenge in contemporary medicine, given the limited effectiveness and numerous adverse effects linked to available treatments. Recognizing the potential of the cholinergic pathway as a therapeutic target, the present work evaluates the antinociceptive activity of a combination of
[...] Read more.
Chronic pain presents a major challenge in contemporary medicine, given the limited effectiveness and numerous adverse effects linked to available treatments. Recognizing the potential of the cholinergic pathway as a therapeutic target, the present work evaluates the antinociceptive activity of a combination of Cris-104, a novel α4β2* receptor agonist, and donepezil, a central anticholinesterase agent. Isobolographic analysis revealed that equimolar combination was approximately 10 times more potent than theoretically calculated equipotent additive dose. Administration of Cris-104 and donepezil combination (3 μmol/kg) successfully reversed hyperalgesia and mechanical allodynia observed in rats subjected to spinal nerve ligation (SNL). The combination also modulated neuroinflammation by reducing astrocyte activation, evident in the decreased expression of glial fibrillary acidic protein (GFAP) in the spinal cord. The observed synergism in combining a nicotinic receptor agonist with an anticholinesterase agent underscores its potential for treating chronic pain. This alternative therapeutic distinct advantage, including dose reduction and high selectivity for the receptor, contribute to a more favorable profile with minimized adverse effects.
Full article
(This article belongs to the Special Issue Molecular Mechanisms of Chronic Pain and New Therapeutic Strategies Volume II)
►▼
Show Figures

Figure 1
Open AccessReview
Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells
Biomedicines 2023, 11(12), 3248; https://doi.org/10.3390/biomedicines11123248 - 07 Dec 2023
Abstract
Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3–4 decades, but the
[...] Read more.
Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3–4 decades, but the addition of targeted agents in recent years has led to improved survival in select subsets of patients as well as a better biological understanding of the disease. Currently, one key paradigm of bench-to-bedside practice in the context of adult AML is the focus on leukemia stem cell (LSC)-targeted therapies. Here, we review current and emerging immunotherapies and other targeted agents that are in clinical use for pediatric AML through the lens of what is known (and not known) about their LSC-targeting capability. Based on a growing understanding of pediatric LSC biology, we also briefly discuss potential future agents on the horizon.
Full article
(This article belongs to the Special Issue Pathogenesis and Novel Therapies of Acute Leukemias)
►▼
Show Figures

Figure 1
Open AccessArticle
Butyrylcarnitine Elevation in Newborn Screening: Reducing False Positives and Distinguishing between Two Rare Diseases through the Evaluation of New Ratios
by
, , , , , and
Biomedicines 2023, 11(12), 3247; https://doi.org/10.3390/biomedicines11123247 - 07 Dec 2023
Abstract
One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of
[...] Read more.
One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust biomarkers in evaluations. Another challenge is how to distinguish between diseases which share the same primary marker and for which secondary biomarkers are just as highly desirable. Focusing on pathologies that involve butyrylcarnitine (C4) elevation, such as short-chain acylCoA dehydrogenase deficiency (SCADD) and isobutyrylCoA dehydrogenase deficiency (IBDD), we investigated the acylcarnitine profile of 121 newborns with a C4 increase to discover secondary markers to achieve two goals: reduce the FP rate and discriminate between the two rare diseases. Analyses were carried out using tandem mass spectrometry with whole blood samples spotted on filter paper. Seven new biomarkers (C4/C0, C4/C5, C4/C5DC\C6OH, C4/C6, C4/C8, C4/C14:1, C4/C16:1) were identified using a non-parametric ANOVA analysis. Then, the corresponding cut-off values were found and applied to the screening program. The seven new ratios were shown to be robust (p < 0.001 and p < 0.01, 0.0937 < ε2 < 0.231) in discriminating between FP and IBDD patients, FP and SCADD patients, or SCADD and IBDD patients. Our results suggest that the new ratios are optimal indicators for identifying true positives, distinguishing between two rare diseases that share the same primary biomarker, improving the predictive positive value (PPV) and reducing the false positive rate (FPR).
Full article
(This article belongs to the Topic Biomarker Development and Application)
►▼
Show Figures

Figure 1
Open AccessArticle
A Retrospective Histological Study on Palatal and Gingival Mucosa Changes during a Rapid Palatal Expansion Procedure
by
, , , , , and
Biomedicines 2023, 11(12), 3246; https://doi.org/10.3390/biomedicines11123246 - 07 Dec 2023
Abstract
The most common inflammatory reactions in the oral mucosa are found at the gingival level. The treatment of these inflammations requires, first of all, the removal of the causative factor; often, this maneuver is sufficient. The aim of this retrospective study was to
[...] Read more.
The most common inflammatory reactions in the oral mucosa are found at the gingival level. The treatment of these inflammations requires, first of all, the removal of the causative factor; often, this maneuver is sufficient. The aim of this retrospective study was to evaluate clinical and histopathological changes that occur in terms of gingival and palatal mucosa enlargement during palatal expansion treatment and their evolution during treatment. Twenty-five (n = 25) research participants, aged between thirteen and twenty-six years old, were examined in this retrospective study. At the end of the treatment, fragments of tissue from the affected level were obtained via incisional biopsy and sent to the histopathology laboratory for a specialized examination. The changes identified were specific to mechanical traumatic injuries, thus excluding hyperplasia from other etiologies (infectious, tumoral, or non-mechanical traumatic). The examined fragments showed hyperplasia. The histopathological examination revealed the mechanical character of the lesion, strengthening the causal relationship between the insertion of the expander and the occurrence of hyperplasia of the palatal mucosa. The type of palatal expander influenced the degree of inflammation, with the severity of hyperplasia being more pronounced in the case of mini-implant-anchored rapid palatal expander (MARPE) usage than in the case of tooth-borne rapid palatal expander (RPE) usage. The analysis of the distance between the expander and the palatal mucosa did not provide conclusive results; the incidence and severity of the reaction were variable in patients with the same distance between the expander and the palatal or gingival mucosa.
Full article
(This article belongs to the Special Issue Progress in Biomaterials and Technologies in Dentistry)
►▼
Show Figures

Figure 1
Open AccessArticle
Effect of CYP2C19 Pharmacogenetic Testing on Predicting Citalopram and Escitalopram Tolerability and Efficacy: A Retrospective, Longitudinal Cohort Study
by
, , , , , and
Biomedicines 2023, 11(12), 3245; https://doi.org/10.3390/biomedicines11123245 - 07 Dec 2023
Abstract
Background—Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs’ efficacy and tolerability. Aim—The aim of this study was to evaluate
[...] Read more.
Background—Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs’ efficacy and tolerability. Aim—The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods—In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual’s metabolizing status for CYP2D6/CYP2C19. Results—With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56–0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions—We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.
Full article
(This article belongs to the Section Drug Metabolism)
►▼
Show Figures

Figure 1
Open AccessArticle
Urinary Collectrin as Promising Biomarker for Acute Kidney Injury in Patients Undergoing Cardiac Surgery
by
, , , , , , , , , and
Biomedicines 2023, 11(12), 3244; https://doi.org/10.3390/biomedicines11123244 - 07 Dec 2023
Abstract
Background: Early detection of acute kidney injury (AKI) is crucial for timely intervention and improved patient outcomes after cardiac surgery. This study aimed to evaluate the potential of urinary collectrin as a novel biomarker for AKI in this patient population. Methods: In this
[...] Read more.
Background: Early detection of acute kidney injury (AKI) is crucial for timely intervention and improved patient outcomes after cardiac surgery. This study aimed to evaluate the potential of urinary collectrin as a novel biomarker for AKI in this patient population. Methods: In this prospective, observational cohort study, 63 patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) were studied at the Medical University of Vienna between 2016 and 2018. We collected urine samples prospectively at four perioperative time points, and urinary collectrin was measured using an enzyme-linked immunosorbent assay. Patients were divided into two groups, AKI and non-AKI, defined by Kidney Disease: Improving Global Outcomes Guidelines, and differences between groups were analyzed. Results: Postoperative AKI was found in 19 (30%) patients. Urine sample analysis revealed an inverse correlation between urinary collectrin and creatinine and AKI stages, as well as significant changes in collectrin levels during the perioperative course. Baseline collectrin levels were 5050 ± 3294 pg/mL, decreased after the start of CPB, reached their nadir at the end of surgery, and began to recover slightly on postoperative day (POD) 1. The most effective timepoint for distinguishing between AKI and non-AKI patients based on collectrin levels was POD 1, with collectrin levels of 2190 ± 3728 pg/mL in AKI patients and 3768 ± 3435 pg/mL in non-AKI patients (p = 0.01). Conclusions: Urinary collectrin shows promise as a novel biomarker for the early detection of AKI in patients undergoing cardiac surgery on CPB. Its dynamic changes throughout the perioperative period, especially on POD 1, provide valuable insights for timely diagnosis and intervention. Further research and validation studies are needed to confirm its clinical usefulness and potential impact on patient outcomes
Full article
(This article belongs to the Topic Nephrology and Dialysis: From Bench to Bedside)
►▼
Show Figures

Figure 1
Open AccessArticle
Networking to Optimize Dmd exon 53 Skipping in the Brain of mdx52 Mouse Model
by
, , , , , , , , , , , , , , and
Biomedicines 2023, 11(12), 3243; https://doi.org/10.3390/biomedicines11123243 - 07 Dec 2023
Abstract
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that disrupt the open reading frame and thus prevent production of functional dystrophin proteins. Recent advances in DMD treatment, notably exon skipping and AAV gene therapy, have achieved some success aimed
[...] Read more.
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that disrupt the open reading frame and thus prevent production of functional dystrophin proteins. Recent advances in DMD treatment, notably exon skipping and AAV gene therapy, have achieved some success aimed at alleviating the symptoms related to progressive muscle damage. However, they do not address the brain comorbidities associated with DMD, which remains a critical aspect of the disease. The mdx52 mouse model recapitulates one of the most frequent genetic pathogenic variants associated with brain involvement in DMD. Deletion of exon 52 impedes expression of two brain dystrophins, Dp427 and Dp140, expressed from distinct promoters. Interestingly, this mutation is eligible for exon skipping strategies aimed at excluding exon 51 or 53 from dystrophin mRNA. We previously showed that exon 51 skipping can restore partial expression of internally deleted yet functional Dp427 in the brain following intracerebroventricular (ICV) injection of antisense oligonucleotides (ASO). This was associated with a partial improvement of anxiety traits, unconditioned fear response, and Pavlovian fear learning and memory in the mdx52 mouse model. In the present study, we investigated in the same mouse model the skipping of exon 53 in order to restore expression of both Dp427 and Dp140. However, in contrast to exon 51, we found that exon 53 skipping was particularly difficult in mdx52 mice and a combination of multiple ASOs had to be used simultaneously to reach substantial levels of exon 53 skipping, regardless of their chemistry (tcDNA, PMO, or 2′MOE). Following ICV injection of a combination of ASO sequences, we measured up to 25% of exon 53 skipping in the hippocampus of treated mdx52 mice, but this did not elicit significant protein restoration. These findings indicate that skipping mouse dystrophin exon 53 is challenging. As such, it has not yet been possible to answer the pertinent question whether rescuing both Dp427 and Dp140 in the brain is imperative to more optimal treatment of neurological aspects of dystrophinopathy.
Full article
(This article belongs to the Special Issue Muscular Dystrophies: Pathophysiology and Therapy)
►▼
Show Figures

Figure 1
Open AccessArticle
Prevalence and Factors Associated with Metabolic Syndrome among Non-Diabetic Saudi Adults: A Cross-Sectional Study
by
, , , , , , , , , , and
Biomedicines 2023, 11(12), 3242; https://doi.org/10.3390/biomedicines11123242 - 07 Dec 2023
Abstract
(1) Introduction: given the high prevalence of metabolic syndrome (MetS) in Saudi Arabia, especially in Jeddah, this study aims to understand the dietary and lifestyle-related risk factors among Jeddah’s non-diabetic adults. (2) Material and Methods: Employing a cross-sectional design, non-diabetic adults were sourced
[...] Read more.
(1) Introduction: given the high prevalence of metabolic syndrome (MetS) in Saudi Arabia, especially in Jeddah, this study aims to understand the dietary and lifestyle-related risk factors among Jeddah’s non-diabetic adults. (2) Material and Methods: Employing a cross-sectional design, non-diabetic adults were sourced from public healthcare centers. Demographics, lifestyle, and dietary habits were surveyed. Blood pressure, anthropometrics, and fasting blood samples measuring plasma glucose, serum triglycerides, and HDL cholesterol were collected. The age cut-off for MetS was ascertained using the receiver operating characteristic curve. Variables influencing MetS were evaluated using univariate logistic regression, and consequential factors underwent multivariate analysis, adjusted for age and sex. (3) Results: Among 1339 participants, 16% had MetS, with age being the strongest predictor (p < 0.001). The optimal age cut-off was 32 years. For those <32, elevated BP in men and waist circumference (WC) in women were most prevalent. For those >32, elevated WC was dominant in both sexes. Univariate logistic regression revealed that higher income and education correlated with lower MetS prevalence, while marriage and smoking were risk factors. Adjusting for age and sex, only very high income had a significant low-risk association (p = 0.034). (4) Conclusion: MetS is notable in the studied group, with age as the pivotal predictor. High income reduces MetS risk, while marital status and smoking could increase it. Since this was a cross-sectional study, cohort studies are needed to validate our findings.
Full article
(This article belongs to the Special Issue Recent Advances in Obesity-Related Metabolic Diseases)
►▼
Show Figures

Figure 1
Open AccessReview
The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex
by
, , , , , , , , , and
Biomedicines 2023, 11(12), 3241; https://doi.org/10.3390/biomedicines11123241 - 07 Dec 2023
Abstract
Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin
[...] Read more.
Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin–hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.
Full article
(This article belongs to the Special Issue Advance in Genetic Research of Epilepsy)
►▼
Show Figures

Figure 1
Open AccessReview
The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity
Biomedicines 2023, 11(12), 3240; https://doi.org/10.3390/biomedicines11123240 - 07 Dec 2023
Abstract
Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted
[...] Read more.
Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.
Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis and Radiotherapy)
►▼
Show Figures

Figure 1
Open AccessArticle
Characterization of the circRNA Landscape in Interleukin-4 Induced Anti-Inflammatory Microglia
Biomedicines 2023, 11(12), 3239; https://doi.org/10.3390/biomedicines11123239 - 07 Dec 2023
Abstract
Microglia are resident innate immune cells that play an essential role in the development and surveillance of the central nervous system as well as the shared pathogenesis of neurodegenerative diseases. Microglia rapidly respond to multiple inflammatory stimuli and activate towards different phenotypes, such
[...] Read more.
Microglia are resident innate immune cells that play an essential role in the development and surveillance of the central nervous system as well as the shared pathogenesis of neurodegenerative diseases. Microglia rapidly respond to multiple inflammatory stimuli and activate towards different phenotypes, such as pro-inflammatory and anti-inflammatory phenotypes. Cytokines, epigenetic and long non-coding RNA modulations have been shown to regulate microglial activation; however, the role of circRNAs in microglia-mediated neuroinflammation remains elusive. Here, we performed circRNA sequencing in IL-4-treated anti-inflammatory microglia and discovered 120 differentially expressed circRNAs. We systemically verified the identities of circRNAs by assays of PCR, RNase R treatment and fluorescent in situ hybridization (FISH), among others. We found that circAdgre1 promoted IL-4-induced anti-inflammatory responses and further conferred neuroprotective effects upon lipopolysaccharide (LPS) stimuli. Taken together, our results show that circRNAs might be possible therapeutic targets for microglia-mediated neuroinflammation and neurodegenerative diseases.
Full article
(This article belongs to the Special Issue The Role of Microglia in Human Diseases)
►▼
Show Figures

Figure 1

Journal Menu
► ▼ Journal Menu-
- Biomedicines Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
BioMed, Biomedicines, BioMedInformatics, Epidemiologia, JCM
Health Informatics and Epidemiological Data Analysis in COVID-19 Based Internet of Medical Things (HIEDA-COVID19-IOMT)
Topic Editors: Wenjun (Chris) Zhang, Dhanjoo N. Ghista, Kelvin K.L. Wong, Zhili SunDeadline: 15 December 2023
Topic in
Antibiotics, Biomedicines, Microorganisms, Parasitologia, Pathogens, Vaccines
Advances in Vaccines and Antimicrobial Therapy
Topic Editors: Roberto Paganelli, Raffaele D’AmelioDeadline: 30 December 2023
Topic in
Biomedicines, Cancers, Diagnostics, JCM, Neurology International
Novel Diagnostic and Therapeutic Strategies in Gliomas
Topic Editors: Athanassios P. Kyritsis, George AlexiouDeadline: 31 December 2023
Topic in
Biomedicines, Biomolecules, CIMB, IJMS, Pharmaceuticals
Neuroprotection by Drugs, Nutraceuticals and Physical Activity, 2nd Volume
Topic Editors: Cristina Angeloni, Andrea TarozziDeadline: 31 January 2024

Conferences
Special Issues
Special Issue in
Biomedicines
10th Anniversary of Biomedicines—Mitochondrial Biology
Guest Editor: Marie-Pierre Golinelli-CohenDeadline: 15 December 2023
Special Issue in
Biomedicines
New Perspectives on Neuronal Cytoskeletal Dysregulation in Health and Disease
Guest Editors: Arjun Singh, Rajvir SinghDeadline: 20 December 2023
Special Issue in
Biomedicines
Alternate Therapies and Proteomics/Genomics Studies of Cancer
Guest Editor: Raji SundararajanDeadline: 31 December 2023
Special Issue in
Biomedicines
Advances in Immunotherapy and Radiation Therapy for Cancer
Guest Editors: Ivaylo B. Mihaylov, Benjamin SpielerDeadline: 15 January 2024
Topical Collections
Topical Collection in
Biomedicines
OMICs and Complex Diseases
Collection Editors: Mostafa Dianatinasab, Anke Wesselius, Amin Salehi-Abargouei
Topical Collection in
Biomedicines
Feature Papers in Cancer Biology and Therapeutics
Collection Editor: Veronique Baud
Topical Collection in
Biomedicines
Feature Papers in Gene and Cell Therapy
Collection Editor: Bernard Lebleu
Topical Collection in
Biomedicines
Feature Papers in Microbiology in Human Health and Disease
Collection Editor: Ryota Niikura