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
Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS
Biomedicines 2024, 12(5), 1017; https://doi.org/10.3390/biomedicines12051017 (registering DOI) - 05 May 2024
Abstract
The current knowledge on pathogenic mechanisms in amyotrophic lateral sclerosis (ALS) has widely been derived from studies with cell and animal models bearing ALS-linked genetic mutations. However, it remains unclear to what extent these disease models are of relevance to sporadic ALS. Few
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The current knowledge on pathogenic mechanisms in amyotrophic lateral sclerosis (ALS) has widely been derived from studies with cell and animal models bearing ALS-linked genetic mutations. However, it remains unclear to what extent these disease models are of relevance to sporadic ALS. Few years ago, we reported that the cerebrospinal fluid (CSF) from sporadic ALS patients contains toxic factors for disease transmission in mice via chronic intracerebroventricular (i.c.v.) infusion. Thus a 14-day i.c.v. infusion of pooled CSF samples from ALS cases in mice provoked motor impairment as well as ALS-like pathological features. This offers a unique paradigm to test therapeutics in the context of sporadic ALS disease. Here, we tested a new Withaferin-A analog (IMS-088) inhibitor of NF-κB that was found recently to mitigate disease phenotypes in mouse models of familial disease expressing TDP-43 mutant. Our results show that oral intake of IMS-088 ameliorated motor performance of mice infused with ALS-CSF and it alleviated pathological changes including TDP-43 proteinopathy, neurofilament disorganization, and neuroinflammation. Moreover, CSF infusion experiments were carried out with transgenic mice having neuronal expression of tagged ribosomal protein (hNfL-RFP mice), which allowed immunoprecipitation of neuronal ribosomes for analysis by mass spectrometry of the translational peptide signatures. The results indicate that treatment with IMS-088 prevented many proteomic alterations associated with exposure to ALS-CSF involving pathways related to cytoskeletal changes, inflammation, metabolic dysfunction, mitochondria, UPS, and autophagy dysfunction. The effective disease-modifying effects of this drug in a mouse model based on i.c.v. infusion of ALS-CSF suggest that the NF-κB signaling pathway represents a compelling therapeutic target for sporadic ALS.
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(This article belongs to the Special Issue New Insights into Motor Neuron Diseases)
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Exposure to a Low-Oxygen Environment Causes Implantation Failure and Transcriptomic Shifts in Mouse Uteruses and Ovaries
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Asmaa Y. Ammar, Fatma M. Minisy, Hossam H. Shawki, Mohamed Mansour, Shabaan A. Hemeda, Abeer F. El Nahas, Ahmed H. Sherif and Hisashi Oishi
Biomedicines 2024, 12(5), 1016; https://doi.org/10.3390/biomedicines12051016 (registering DOI) - 05 May 2024
Abstract
Hypoxia is a condition in which tissues of the body do not receive sufficient amounts of oxygen supply. Numerous studies have elucidated the intricate roles of hypoxia and its involvement in both physiological and pathological conditions. This study aimed to clarify the impact
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Hypoxia is a condition in which tissues of the body do not receive sufficient amounts of oxygen supply. Numerous studies have elucidated the intricate roles of hypoxia and its involvement in both physiological and pathological conditions. This study aimed to clarify the impact of a forced low-oxygen environment in early pregnancy by exposing mice to low-oxygen conditions for 24–72 h after fertilization. The treatment resulted in the complete failure of blastocyst implantation, accompanied by vascular hyperpermeability in the uterus. A transcriptome analysis of the uterus revealed remarkable alterations in gene expression between control normoxic- and hypoxic-treatment groups. These alterations were characterized by the differentially expressed genes categorized into the immune responses and iron coordination. Furthermore, exposure to a low-oxygen environment caused apoptosis in the corpus luteum within the ovary and a reduction in progesterone secretion. Consequently, diminished plasma progesterone levels were considered to contribute to implantation failure in combination with the activation of the hypoxic pathway in the uterus. Additionally, previous studies have demonstrated the impact of hypoxic reactions on blastocyst development and the pre-implantation process in the endometrium. Our findings suggest that the corpus luteum exhibits elevated susceptibility to hypoxia, thereby elucidating a critical aspect of its physiological response.
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(This article belongs to the Section Molecular and Translational Medicine)
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The Intrarenal Reflux Diagnosed by Contrast-Enhanced Voiding Urosonography (ceVUS): A Reason for the Reclassification of Vesicoureteral Reflux and New Therapeutic Approach?
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Marijan Saraga, Mirna Saraga-Babić, Adela Arapović, Katarina Vukojević, Zenon Pogorelić and Ana Simičić Majce
Biomedicines 2024, 12(5), 1015; https://doi.org/10.3390/biomedicines12051015 (registering DOI) - 05 May 2024
Abstract
Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result
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Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.
Full article
(This article belongs to the Special Issue Recent Advances in Kidney Disease in Children)
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Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up
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Mehmet Ali Kazgı, Ertugrul Bayram, Tolga Kosecı, Burak Mete, Tugba Toyran, Melek Ergin and Ismail Oguz Kara
Biomedicines 2024, 12(5), 1014; https://doi.org/10.3390/biomedicines12051014 (registering DOI) - 04 May 2024
Abstract
(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate
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(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients’ life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.
Full article
(This article belongs to the Section Cancer Biology and Oncology)
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Open AccessCommunication
Rikkosan’s Short-Term Analgesic Effect on Burning Mouth Syndrome: A Single-Arm Cohort Study
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Tatsuki Itagaki, Keisuke Nakamura, Tougo Tanabe, Takumi Shimura, Yu Nakai, Ken-ichiro Sakata, Jun Sato and Yoshimasa Kitagawa
Biomedicines 2024, 12(5), 1013; https://doi.org/10.3390/biomedicines12051013 (registering DOI) - 04 May 2024
Abstract
Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this
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Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (−2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.
Full article
(This article belongs to the Special Issue Chronic Pain: From Prevention to Therapeutic Strategies—Second Edition)
Open AccessArticle
Ibrutinib Modulates Proliferation, Migration, Mitochondrial Homeostasis, and Apoptosis in Melanoma Cells
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Fernanda Vitelli Lins, Elizabete Cristina Iseke Bispo, Naomí Souza Rodrigues, Maria Victória Souto Silva, Juliana Lott Carvalho, Guilherme Martins Gelfuso and Felipe Saldanha-Araujo
Biomedicines 2024, 12(5), 1012; https://doi.org/10.3390/biomedicines12051012 (registering DOI) - 04 May 2024
Abstract
Ibrutinib, a tyrosine kinase inhibitor with a broad spectrum of action, has been successfully explored to treat hematological and solid cancers. Herein, we investigated the anti-cancer effect of Ibrutinib on melanoma cell lines. Cytotoxicity was evaluated using the MTT assay. Apoptosis, mitochondrial membrane
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Ibrutinib, a tyrosine kinase inhibitor with a broad spectrum of action, has been successfully explored to treat hematological and solid cancers. Herein, we investigated the anti-cancer effect of Ibrutinib on melanoma cell lines. Cytotoxicity was evaluated using the MTT assay. Apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) production, cell proliferation, and cell cycle stages were determined by flow cytometry. LDH release and Caspase 3/7 activity were determined by colorimetric and luminescent assays, respectively. Cell migration was evaluated by wound scratch assay. Gene expression was determined by real-time PCR. Gene Ontology (GO) enrichment analysis of melanoma clinical samples was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). MTT assays showed that Ibrutinib is toxic for MeWo, SK-MEL-28, and WM164 cells. The annexin V/PI staining, Caspase 3/7 activity, and LDH release in MeWo cells revealed that apoptosis is the primary mechanism of death caused by Ibrutinib. Corroborating such observation, we identified that Ibrutinib treatment impairs the mitochondrial membrane potential of such cells and significantly increases the transcriptional levels of the pro-apoptotic factors ATM, HRK, BAX, BAK, CASP3, and CASP8. Furthermore, Ibrutinib showed antimetastatic potential by inhibiting the migration of MeWo cells. Finally, we performed a functional enrichment analysis and identified that the differential expression of Ibrutinib-target molecules is associated with enrichment of apoptosis and necrosis pathways in melanoma samples. Taken together, our results clearly suggest that Ibrutinib can be successfully explored as an effective therapeutic approach for melanomas.
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(This article belongs to the Section Cancer Biology and Oncology)
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Modulation of Epithelial–Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel
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Hajime Nakamura, Megumi Watanabe, Kohichi Takada, Tatsuya Sato, Fumihito Hikage, Araya Umetsu, Joji Muramatsu, Masato Furuhashi and Hiroshi Ohguro
Biomedicines 2024, 12(5), 1011; https://doi.org/10.3390/biomedicines12051011 - 03 May 2024
Abstract
To elucidate the currently unknown molecular mechanisms responsible for the similarity and difference during the acquirement of resistance against gemcitabine (GEM) and paclitaxel (PTX) in patients with pancreatic carcinoma, we examined two-dimensional (2D) and three-dimensional (3D) cultures of parent MIA PaCa-2 cells (MIA
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To elucidate the currently unknown molecular mechanisms responsible for the similarity and difference during the acquirement of resistance against gemcitabine (GEM) and paclitaxel (PTX) in patients with pancreatic carcinoma, we examined two-dimensional (2D) and three-dimensional (3D) cultures of parent MIA PaCa-2 cells (MIA PaCa-2-PA) and their GEM resistance cell line (MIA PaCa-2-GR) and PTX resistance (MIA PaCa-2-PR). Using these cells, we examined 3D spheroid configurations and cellular metabolism, including mitochondrial and glycolytic functions, with a Seahorse bio-analyzer and RNA sequencing analysis. Compared to the MIA PaCa-2-PA, (1) the formation of the 3D spheroids of MIA PaCa-2-GR or -PR was much slower, and (2) their mitochondrial and glycolytic functions were greatly modulated in MIA PaCa-2-GR or -PR, and such metabolic changes were also different between their 2D and 3D culture conditions. RNA sequencing and bioinformatic analyses of the differentially expressed genes (DEGs) using an ingenuity pathway analysis (IPA) suggested that various modulatory factors related to epithelial –mesenchymal transition (EMT) including STAT3, GLI1, ZNF367, NKX3-2, ZIC2, IFIT2, HEY1 and FBLX, may be the possible upstream regulators and/or causal network master regulators responsible for the acquirement of drug resistance in MIA PaCa-2-GR and -PR. In addition, among the prominently altered DEGs (Log2 fold changes more than 6 or less than −6), FABP5, IQSEC3, and GASK1B were identified as unique genes associated with their antisense RNA or pseudogenes, and among these, FABP5 and GASK1B are known to function as modulators of cancerous EMT. Therefore, the observations reported herein suggest that modulations of cancerous EMT may be key molecular mechanisms that are responsible for inducing chemoresistance against GEM or PTX in MIA PaCa-2 cells.
Full article
(This article belongs to the Special Issue Cancer Metabolism and Resistance to Cell Death: Novel Therapeutic Perspectives 2nd Edition)
Open AccessArticle
Rats Orally Administered with Ethyl Alcohol for a Prolonged Time Show Histopathology of the Epididymis and Seminal Vesicle Together with Changes in the Luminal Metabolite Composition
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Chayakorn Taoto, Nareelak Tangsrisakda, Wipawee Thukhammee, Jutarop Phetcharaburanin, Sitthichai Iamsaard and Nongnuj Tanphaichitr
Biomedicines 2024, 12(5), 1010; https://doi.org/10.3390/biomedicines12051010 - 03 May 2024
Abstract
Prolonged ethanol (EtOH) consumption is associated with male infertility, with a decreased spermatogenesis rate as one cause. The defective maturation and development of sperm during their storage in the cauda epididymis and transit in the seminal vesicle can be another cause, possibly occurring
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Prolonged ethanol (EtOH) consumption is associated with male infertility, with a decreased spermatogenesis rate as one cause. The defective maturation and development of sperm during their storage in the cauda epididymis and transit in the seminal vesicle can be another cause, possibly occurring before the drastic spermatogenesis disruption. Herein, we demonstrated that the cauda epididymis and seminal vesicle of rats, orally administered with EtOH under a regimen in which spermatogenesis was still ongoing, showed histological damage, including lesions, a decreased height of the epithelial cells and increased collagen fibers in the muscle layer, which implicated fibrosis. Lipid peroxidation (shown by malondialdehyde (MDA) levels) was observed, indicating that reactive oxygen species (ROS) were produced along with acetaldehyde during EtOH metabolism by CYP2E1. MDA, acetaldehyde and other lipid peroxidation products could further damage cellular components of the cauda epididymis and seminal vesicle, and this was supported by increased apoptosis (shown by a TUNEL assay and caspase 9/caspase 3 expression) in these two tissues of EtOH-treated rats. Consequently, the functionality of the cauda epididymis and seminal vesicle in EtOH-treated rats was impaired, as demonstrated by a decreases in 1H NMR-analyzed metabolites (e.g., carnitine, fructose), which were important for sperm development, metabolism and survival in their lumen.
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(This article belongs to the Special Issue Molecular Regulation of Spermatozoa)
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Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling
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Federica Mannino, Valentina Urzì Brancati, Rita Lauro, Igor Pirrotta, Michelangelo Rottura, Natasha Irrera, Gian Maria Cavallini, Giovanni Pallio, Eloisa Gitto and Sara Manti
Biomedicines 2024, 12(5), 1009; https://doi.org/10.3390/biomedicines12051009 - 03 May 2024
Abstract
Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system
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Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system (CNS). Levosimendan, a cardioprotective inodilator, and dobutamine, a β1-adrenergic agonist, are commonly used for the treatment of hypovolemic shock, thanks to their anti-inflammatory and antioxidant effects. For this reason, we aimed at investigating levosimendan and dobutamine’s neuroprotective effects in an “in vitro” model of lipopolysaccharide (LPS)-induced neuroinflammation. Human microglial cells (HMC3) were challenged with LPS (0.1 µg/mL) to induce an inflammatory phenotype and then treated with levosimendan (10 µM) or dobutamine (50 µM) for 24 h. Levosimendan and dobutamine significantly reduced the ROS levels and markedly increased Nrf2 and HO-1 protein expression in LPS-challenged cells. Levosimendan and dobutamine also decreased p-NF-κB expression and turned off the NLRP3 inflammasome together with its downstream signals, caspase-1 and IL-1β. Moreover, a reduction in TNF-α and IL-6 expression and an increase in IL-10 levels in LPS-stimulated HMC3 cells was observed following treatment. In conclusion, levosimendan and dobutamine attenuated LPS-induced neuroinflammation through NF-κB pathway inhibition and NLRP3 inflammasome activation via Nrf2/HO-1 signalling, suggesting that these drugs could represent a promising therapeutic approach for the treatment of neuroinflammation consequent to hypovolemic shock.
Full article
(This article belongs to the Special Issue Neuroinflammation: From Pathophysiologic Mechanisms to Therapeutic Strategies)
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Marijuana Use May Be Associated with Reduced Prevalence of Prostate Cancer: A National Survey on Drug Use and Health Study from United States of America
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Turab Mohammed, James Yu, Yong Qiao, Youngchul Kim, Eric Mortensen, Helen Swede, Zhao Wu and Jingsong Zhang
Biomedicines 2024, 12(5), 1008; https://doi.org/10.3390/biomedicines12051008 - 03 May 2024
Abstract
Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use
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Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50–64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62–0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52–1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.
Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis)
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Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Hydrolyze Recombinant RBD and Nucleocapsid (N) Proteins
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Anna M. Timofeeva, Liliya Sh. Shayakhmetova, Artem O. Nikitin, Tatyana A. Sedykh, Andrey L. Matveev, Daniil V. Shanshin, Ekaterina A. Volosnikova, Iuliia A. Merkuleva, Dmitriy N. Shcherbakov, Nina V. Tikunova, Sergey E. Sedykh and Georgy A. Nevinsky
Biomedicines 2024, 12(5), 1007; https://doi.org/10.3390/biomedicines12051007 - 02 May 2024
Abstract
Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma
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Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization.
Full article
(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)
Open AccessArticle
Saliva as a Diagnostic Tool for Early Detection of Exercise-Induced Oxidative Damage in Female Athletes
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Aleksandr N. Ovchinnikov and Antonio Paoli
Biomedicines 2024, 12(5), 1006; https://doi.org/10.3390/biomedicines12051006 - 02 May 2024
Abstract
Although blood still remains the most commonly utilized medium to detect increased levels of oxidative damage induced by exercise, saliva diagnostics have gained increasing popularity due to their non-invasive nature and athlete-friendly collection process. Given that the contribution of various phases of the
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Although blood still remains the most commonly utilized medium to detect increased levels of oxidative damage induced by exercise, saliva diagnostics have gained increasing popularity due to their non-invasive nature and athlete-friendly collection process. Given that the contribution of various phases of the menstrual cycle to the levels of oxidative damage may differ, the aim of this study was to evaluate an agreement between salivary and plasmatic levels of lipid peroxidation products in female swimmers in both the follicular (F) and luteal (L) phases of the menstrual cycle at rest and following exercise. Twelve well-trained female swimmers aged 19.6 ± 1.1 years old were examined. We measured diene conjugates (DCs), triene conjugates (TCs), and Schiff bases (SBs) in lipids immediately after their extraction from both saliva and blood plasma. All female swimmers were studied two times each, in the two different phases of one menstrual cycle, before and after high-intensity interval exercise (HIIE). Salivary and plasmatic levels of DCs, TCs, and SBs significantly increased post-exercise compared to pre-exercise, in both the F and L phases. A high positive correlation was observed between the concentrations of DCs, TCs, and SBs in the saliva and blood plasma of participants in the F and L phases, both at rest and following HIIE. Ordinary least products regression analysis indicates that there was no proportional and differential bias in the data. The Bland–Altman method also declares that there was no differential bias, since the line of equality was within the 95% confidence interval of the mean difference between salivary and plasmatic levels of DCs, TCs, and SBs in female swimmers, in both the F and L phases, before and after HIIE. There was also no proportional bias in the Bland–Altman plots. Thus, this is the first study to report a high agreement between the quantifications of DCs, TCs, and SBs in the saliva and blood plasma of female swimmers in both the F and L phases, at rest and following HIIE.
Full article
(This article belongs to the Topic Oxidative Stress and Inflammation, 2nd Volume)
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Open AccessArticle
Improved Ultrasound-Guided Balloon-Assisted Maturation Angioplasty Using Drug-Eluting Balloons in the First Autogenous Arteriovenous Fistula Procedure: Early Experience
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Domenico Mirabella, Ettore Dinoto, Edoardo Rodriquenz, Michele Bellomo, Andrea Miccichè, Paolo Annicchiarico and Felice Pecoraro
Biomedicines 2024, 12(5), 1005; https://doi.org/10.3390/biomedicines12051005 - 02 May 2024
Abstract
In patients with end-stage renal failure requiring hemodialysis, autogenous arteriovenous fistula (AVF) is preferred over tunneled dialysis catheters due to lower complications and costs. However, AVF maturation failure remains a common issue due to small vein size, multiple venipunctures, and other factors. Guidelines
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In patients with end-stage renal failure requiring hemodialysis, autogenous arteriovenous fistula (AVF) is preferred over tunneled dialysis catheters due to lower complications and costs. However, AVF maturation failure remains a common issue due to small vein size, multiple venipunctures, and other factors. Guidelines recommend using vessels of >2 mm for forearm AVFs and >3 mm for upper arm AVFs. This study investigates the use of intraoperative Doppler ultrasound (DUS)-guided Balloon-Assisted Maturation (BAM) with drug-eluting balloons (DEB) during initial AVF creation. Data from 114 AVF procedures, of which 27.2% underwent BAM, were analyzed. BAM was performed in 25 distal radio-cephalic and 6 proximal brachio-cephalic AVFs. With DUS guidance, vein stenosis was identified and treated using DEB. Technical success was achieved in all cases, with no early mortality. Early BAM-related complications were minimal, and no AVF thrombosis occurred. AVF maturation time was 15 days (SD: 3), and no further complications were reported during a mean follow-up of 10.38 months. Using BAM with DEB during AVF creation led to successful maturation and dialysis use without the need for secondary procedures. This study emphasizes the importance of identifying AVF failure risk early and utilizing DUS-guided procedures to enhance AVF outcomes. A more liberal use of intraoperative BAM could limit reinterventions in patients undergoing AVFs.
Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)
Open AccessArticle
Point-of-Care Serum Proenkephalin as an Early Predictor of Mortality in Patients Presenting to the Emergency Department with Septic Shock
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Christos Verras, Sofia Bezati, Vasiliki Bistola, Ioannis Ventoulis, Dionysis Matsiras, Sotirios Tsiodras, John Parissis and Effie Polyzogopoulou
Biomedicines 2024, 12(5), 1004; https://doi.org/10.3390/biomedicines12051004 - 02 May 2024
Abstract
Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured
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Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.
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(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)
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A Novel RP-UHPLC-MS/MS Approach for the Determination of Tryptophan Metabolites Derivatized with 2-Bromo-4′-Nitroacetophenone
by
Timotej Jankech, Ivana Gerhardtova, Petra Majerova, Juraj Piestansky, Lubica Fialova, Josef Jampilek and Andrej Kovac
Biomedicines 2024, 12(5), 1003; https://doi.org/10.3390/biomedicines12051003 - 02 May 2024
Abstract
Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise and reliable methods for their determination are needed. Variability in their physicochemical properties makes the analytical process challenging. In this case, chemical
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Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise and reliable methods for their determination are needed. Variability in their physicochemical properties makes the analytical process challenging. In this case, chemical modification of analyte derivatization could come into play. Here, we introduce a novel fast reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with tandem mass spectrometry (MS/MS) method for the determination of Trp and its ten metabolites in human plasma samples after derivatization with 2-bromo-4′-nitroacetophenone (BNAP). The derivatization procedure was optimized in terms of incubation time, temperature, concentration, and volume of the derivatization reagent. Method development comprises a choice of a suitable stationary phase, mobile phase composition, and gradient elution optimization. The developed method was validated according to the ICH guidelines. Results of all validation parameters were within the acceptance criteria of the guideline, i.e., intra- and inter-day precision (expressed as relative standard deviation; RSD) were in the range of 0.5–8.2% and 2.3–7.4%, accuracy was in the range of 93.3–109.7% and 94.7–110.1%, limits of detection (LODs) were in the range of 0.15–9.43 ng/mL, coefficients of determination (R2) were higher than 0.9906, and carryovers were, in all cases, less than 8.8%. The practicability of the method was evaluated using the blue applicability grade index (BAGI) with a score of 65. Finally, the developed method was used for the analysis of Alzheimer’s disease and healthy control plasma to prove its applicability. Statistical analysis revealed significant changes in picolinic acid (PA), anthranilic acid (AA), 5 hydroxyindole-3-acetic acid (5-OH IAA), and quinolinic acid (QA) concentration levels. This could serve as the basis for future studies that will be conducted with a large cohort of patients.
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(This article belongs to the Special Issue Biomedical and Biochemical Basis of Neurodegenerative Diseases)
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Olfactory Dysfunction and Glaucoma
by
Valeria Iannucci, Alice Bruscolini, Giannicola Iannella, Giacomo Visioli, Ludovico Alisi, Mauro Salducci, Antonio Greco and Alessandro Lambiase
Biomedicines 2024, 12(5), 1002; https://doi.org/10.3390/biomedicines12051002 - 02 May 2024
Abstract
Background: Olfactory dysfunction is a well-known phenomenon in neurological diseases with anosmia and hyposmia serving as clinical or preclinical indicators of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Since glaucoma is a neurodegenerative disease of the visual system, it may also entail
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Background: Olfactory dysfunction is a well-known phenomenon in neurological diseases with anosmia and hyposmia serving as clinical or preclinical indicators of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Since glaucoma is a neurodegenerative disease of the visual system, it may also entail alterations in olfactory function, warranting investigation into potential sensory interconnections. Methods: A review of the current literature of the last 15 years (from 1 April 2008 to 1 April 2023) was conducted by two different authors searching for topics related to olfaction and glaucoma. Results: three papers met the selection criteria. According to these findings, patients with POAG appear to have worse olfaction than healthy subjects. Furthermore, certain predisposing conditions to glaucoma, such as pseudoexfoliation syndrome and primary vascular dysregulation, could possibly induce olfactory changes that can be measured with the Sniffin Stick test. Conclusions: the scientific literature on this topic is very limited, and the pathogenesis of olfactory changes in glaucoma is not clear. However, if the results of these studies are confirmed by further research, olfactory testing may be a non-invasive tool to assist clinicians in the early diagnosis of glaucoma.
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(This article belongs to the Special Issue Glaucoma: New Diagnostic and Therapeutic Approaches)
Open AccessArticle
Effects of Once-Weekly Semaglutide on Cardiovascular Risk Factors and Metabolic Dysfunction-Associated Steatotic Liver Disease in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study Based on Real-World Data
by
Hisayuki Katsuyama, Mariko Hakoshima, Emika Kaji, Masaaki Mino, Eiji Kakazu, Sakura Iida, Hiroki Adachi, Tatsuya Kanto and Hidekatsu Yanai
Biomedicines 2024, 12(5), 1001; https://doi.org/10.3390/biomedicines12051001 - 02 May 2024
Abstract
Once-weekly semaglutide is a widely used glucagon-like peptide-1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes (T2D). In clinical trials, semaglutide improved glycemic control and obesity, and reduced major cardiovascular events. However, the reports are limited on its real-world efficacy
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Once-weekly semaglutide is a widely used glucagon-like peptide-1 receptor agonist (GLP-1RA) used for the treatment of type 2 diabetes (T2D). In clinical trials, semaglutide improved glycemic control and obesity, and reduced major cardiovascular events. However, the reports are limited on its real-world efficacy relating to various metabolic factors such as dyslipidemia or metabolic dysfunction-associated steatotic liver disease (MASLD) in Asian patients with T2D. In our retrospective longitudinal study, we selected patients with T2D who were given once-weekly semaglutide and compared metabolic parameters before and after the start of semaglutide. Seventy-five patients were eligible. HbA1c decreased significantly, by 0.7–0.9%, and body weight by 1.4–1.7 kg during the semaglutide treatment. Non-HDL cholesterol decreased significantly at 3, 6 and 12 months after the initiation of semaglutide; LDL cholesterol decreased at 3 and 6 months; and HDL cholesterol increased at 12 months. The effects on body weight, HbA1c and lipid profile were pronounced in patients who were given semaglutide as a first GLP-1RA (GLP-1R naïve), whereas improvements in HbA1c were also observed in patients who were given semaglutide after being switched from other GLP-1RAs. During a 12-month semaglutide treatment, the hepatic steatosis index (HSI) tended to decrease. Moreover, a significant decrease in the AST-to-platelet ratio index (APRI) was observed in GLP-1RA naïve patients. Our real-world study confirmed the beneficial effects of once-weekly semaglutide, namely, improved body weight, glycemic control and atherogenic lipid profile. The beneficial effects on MASLD were also suggested.
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(This article belongs to the Special Issue New Challenges in the Study of Diabetes and Related Complications-Pathophysiology, Prevention and Treatment)
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Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide
by
Purvi Trivedi, Tanya Myers, Bithika Ray, Matthew Allain, Juan Zhou, Melanie Kelly and Christian Lehmann
Biomedicines 2024, 12(5), 1000; https://doi.org/10.3390/biomedicines12051000 - 02 May 2024
Abstract
Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn’s disease. The inflammation in UC is typically restricted to the
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Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn’s disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.
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(This article belongs to the Section Drug Discovery, Development and Delivery)
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Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies
by
R. John Solaro, Paul H. Goldspink and Beata M. Wolska
Biomedicines 2024, 12(5), 999; https://doi.org/10.3390/biomedicines12050999 - 02 May 2024
Abstract
Novel therapies for the treatment of familial dilated cardiomyopathy (DCM) are lacking. Shaping research directions to clinical needs is critical. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally, these
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Novel therapies for the treatment of familial dilated cardiomyopathy (DCM) are lacking. Shaping research directions to clinical needs is critical. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally, these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment, which over time result in structural and functional maladaptations, leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension-time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly concerning mutant proteins and their impact on sarcomere molecular signaling are currently controversial. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension-generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon the Ca2+ activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale X-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering the control of tension. We discuss these mechanisms that lead to different ideas related to how tension is disturbed by levels of mutant sarcomere proteins linked to the expression of gene variants in the complex landscape of DCM. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.
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(This article belongs to the Special Issue Unraveling the Molecular Mechanisms of Heart and Skeletal Muscle Pathologies)
Open AccessArticle
Seroprevalence and Associated Risk Factors of Toxoplasma gondii in Patients Diagnosed with Schizophrenia: A Case–Control Cross Sectional Study
by
Sebastian Grada, Alin Gabriel Mihu, Daniela Adriana Oatis, Constantin Catalin Marc, Liana Maria Chicea, Cristina Petrescu, Alina Maria Lupu and Tudor Rares Olariu
Biomedicines 2024, 12(5), 998; https://doi.org/10.3390/biomedicines12050998 - 01 May 2024
Abstract
The protozoan parasite, Toxoplasma gondii, has been linked to several psychiatric disorders, including schizophrenia. The aim of this study was to assess the prevalence of T. gondii IgG antibodies and risk factors associated with seroprevalence in patients diagnosed with schizophrenia. This seroepidemiological
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The protozoan parasite, Toxoplasma gondii, has been linked to several psychiatric disorders, including schizophrenia. The aim of this study was to assess the prevalence of T. gondii IgG antibodies and risk factors associated with seroprevalence in patients diagnosed with schizophrenia. This seroepidemiological study assessed 196 participants, divided into two groups. The study group consisted of 98 schizophrenic patients and was matched with 98 healthy blood donors. A questionnaire was used to gather information regarding potential risk factors associated with T. gondii seroprevalence. Results revealed a higher seroprevalence of T. gondii IgG antibodies in schizophrenic patients (69.39%, 68/98) when compared to healthy controls (51.02%, 50/98) (OR: 2.18; 95% CI: 1.21–3.9; p = 0.01). Patients with schizophrenia who consumed raw or undercooked meat (80.65%, 25/31) (OR: 3.75; 95% CI: 1.25–11.21, p = 0.02) and those with a lower educational level (77.59%, 45/58) (OR: 3.5; 95% CI: 1.59–7.54, p = 0.002) presented increased T. gondii seropositivity rates versus their control counterparts. Our findings indicate a high T. gondii IgG seroprevalence in patients diagnosed with schizophrenia compared to healthy blood donors. Factors associated with T. gondii seroprevalence were consumption of raw or uncooked meat and a lower educational attainment. This study provided the first data regarding the potential risk factors for toxoplasmosis in Romanian patients diagnosed with schizophrenia and may serve as a foundation for future research and the development of preventive strategies.
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(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Infectious Diseases)
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