Journal Description
Biomolecules
Biomolecules
is a peer-reviewed, open access journal on structures and functions of bioactive and biogenic substances, molecular mechanisms with biological and medical implications as well as biomaterials and their applications. Biomolecules is published monthly online by MDPI. The Spanish Society for Biochemistry and Molecular Biology (SEBBM) is affiliated with Biomolecules and their 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, MEDLINE, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Biochemistry & Molecular Biology) / CiteScore - Q1 (Biochemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.9 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.
- Sections: published in 19 topical sections.
- Testimonials: See what our editors and authors say about Biomolecules.
- Companion journal: Receptors.
Impact Factor:
5.5 (2022);
5-Year Impact Factor:
5.8 (2022)
Latest Articles
Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice
Biomolecules 2024, 14(4), 494; https://doi.org/10.3390/biom14040494 - 18 Apr 2024
Abstract
Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and
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Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9. Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity. HDAC9 TG mice gained less body weight than wild-type (WT) mice when fed a standard laboratory diet for up to 40 weeks, which was attributed to reduced fat mass (primarily inguinal adipose tissue). There was no difference in insulin sensitivity or glucose tolerance in 18-week-old WT and HDAC9 TG mice; however, at 40 weeks of age, HDAC9 TG mice exhibited impaired insulin sensitivity and glucose intolerance. Tissue histology demonstrated adipocyte hypertrophy, along with reduced numbers of mature adipocytes and stromovascular cells, in the HDAC9 TG mouse adipose tissue. Moreover, increased lipids were detected in the livers of aging HDAC9 TG mice, as evaluated by oil red O staining. In conclusion, the experimental aging HDAC9 TG mice developed adipocyte hypertrophy, insulin resistance, and hepatic steatosis, independent of obesity. This novel mouse model may be useful in the investigation of the impact of Hdac9 overexpression associated with metabolic and aging-related diseases.
Full article
(This article belongs to the Special Issue Recent Advances in Histone Deacetylase Research in Health and Disease)
Open AccessArticle
Mitochondrial Transplantation’s Role in Rodent Skeletal Muscle Bioenergetics: Recharging the Engine of Aging
by
Tasnim Arroum, Gerald A. Hish, Kyle J. Burghardt, James D. McCully, Maik Hüttemann and Moh H. Malek
Biomolecules 2024, 14(4), 493; https://doi.org/10.3390/biom14040493 - 18 Apr 2024
Abstract
Background: Mitochondria are the ‘powerhouses of cells’ and progressive mitochondrial dysfunction is a hallmark of aging in skeletal muscle. Although different forms of exercise modality appear to be beneficial to attenuate aging-induced mitochondrial dysfunction, it presupposes that the individual has a requisite level
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Background: Mitochondria are the ‘powerhouses of cells’ and progressive mitochondrial dysfunction is a hallmark of aging in skeletal muscle. Although different forms of exercise modality appear to be beneficial to attenuate aging-induced mitochondrial dysfunction, it presupposes that the individual has a requisite level of mobility. Moreover, non-exercise alternatives (i.e., nutraceuticals or pharmacological agents) to improve skeletal muscle bioenergetics require time to be effective in the target tissue and have another limitation in that they act systemically and not locally where needed. Mitochondrial transplantation represents a novel directed therapy designed to enhance energy production of tissues impacted by defective mitochondria. To date, no studies have used mitochondrial transplantation as an intervention to attenuate aging-induced skeletal muscle mitochondrial dysfunction. The purpose of this investigation, therefore, was to determine whether mitochondrial transplantation can enhance skeletal muscle bioenergetics in an aging rodent model. We hypothesized that mitochondrial transplantation would result in sustained skeletal muscle bioenergetics leading to improved functional capacity. Methods: Fifteen female mice (24 months old) were randomized into two groups (placebo or mitochondrial transplantation). Isolated mitochondria from a donor mouse of the same sex and age were transplanted into the hindlimb muscles of recipient mice (quadriceps femoris, tibialis anterior, and gastrocnemius complex). Results: The results indicated significant increases (ranging between ~36% and ~65%) in basal cytochrome c oxidase and citrate synthase activity as well as ATP levels in mice receiving mitochondrial transplantation relative to the placebo. Moreover, there were significant increases (approx. two-fold) in protein expression of mitochondrial markers in both glycolytic and oxidative muscles. These enhancements in the muscle translated to significant improvements in exercise tolerance. Conclusions: This study provides initial evidence showing how mitochondrial transplantation can promote skeletal muscle bioenergetics in an aging rodent model.
Full article
(This article belongs to the Special Issue Skeletal Muscle Homeostasis and Regeneration)
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Open AccessArticle
Development of Improved Spectrophotometric Assays for Biocatalytic Silyl Ether Hydrolysis
by
Yuqing Lu, Chisom S. Egedeuzu, Peter G. Taylor and Lu Shin Wong
Biomolecules 2024, 14(4), 492; https://doi.org/10.3390/biom14040492 - 18 Apr 2024
Abstract
Reported herein is the development of assays for the spectrophotometric quantification of biocatalytic silicon−oxygen bond hydrolysis. Central to these assays are a series of chromogenic substrates that release highly absorbing phenoxy anions upon cleavage of the sessile bond. These substrates were tested with
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Reported herein is the development of assays for the spectrophotometric quantification of biocatalytic silicon−oxygen bond hydrolysis. Central to these assays are a series of chromogenic substrates that release highly absorbing phenoxy anions upon cleavage of the sessile bond. These substrates were tested with silicatein, an enzyme from a marine sponge that is known to catalyse the hydrolysis and condensation of silyl ethers. It was found that, of the substrates tested, tert-butyldimethyl(2-methyl-4-nitrophenoxy)silane provided the best assay performance, as evidenced by the highest ratio of enzyme catalysed reaction rate compared with the background (uncatalysed) reaction. These substrates were also found to be suitable for detailed enzyme kinetics measurements, as demonstrated by their use to determine the Michaelis−Menten kinetic parameters for silicatein.
Full article
(This article belongs to the Section Enzymology)
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Open AccessArticle
Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment
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Valeria Bentivoglio, Filippo Galli, Michela Varani, Danilo Ranieri, Pallavi Nayak, Annunziata D’Elia, Andrea Soluri, Roberto Massari, Chiara Lauri and Alberto Signore
Biomolecules 2024, 14(4), 491; https://doi.org/10.3390/biom14040491 - 18 Apr 2024
Abstract
Tumor associated fibroblasts (TAFs) play a key role in tumor growth and metastatization. TAFs overexpress different biomarkers that are usually expressed at low levels in physiological conditions. Among them are the fibroblast growth factor receptors (FGFRs) that bind the fibroblast growth factors (FGFs).
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Tumor associated fibroblasts (TAFs) play a key role in tumor growth and metastatization. TAFs overexpress different biomarkers that are usually expressed at low levels in physiological conditions. Among them are the fibroblast growth factor receptors (FGFRs) that bind the fibroblast growth factors (FGFs). In particular, the overexpression of FGFR-2c in tumors has been associated with advanced clinical stages and increased metastatization. Here, we developed a non-invasive tool to evaluate, in vivo, the expression of FGFR-2c in metastatic cancer. This is based on 99mTc-labelled FGF-2. Methods: 99mTc-FGF-2 was tested in vitro and in vivo in mice bearing allografts of sarcoma cells. Images of 99mTc-FGF-2 were acquired using a new portable high-resolution ultra-sensitive gamma camera for small animal imaging. Results: FGF-2 was labeled with high specific activity but low labelling efficiency, thus requiring post-labeling purification by gel-filtration chromatography. In vitro binding to 2C human keratinocytes showed a Kd of 3.36 × 10−9 M. In mice bearing J774A.1 cell allografts, we observed high and rapid tumor uptake of 99mTc-FGF-2 with a high Tumor/Blood ratio at 24 h post-injection (26.1 %ID/g and 12.9 %ID) with low kidney activity and moderate liver activity. Conclusions: we labeled FGF-2 with 99mTc and showed nanomolar Kd in vitro with human keratinocytes expressing FGF-2 receptors. In mice, 99mTc-FGF-2 rapidly and efficiently accumulated in tumors expressing FGF-2 receptors. This new radiopharmaceutical could be used in humans to image TAFs.
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(This article belongs to the Section Molecular Medicine)
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Open AccessArticle
Elevated Serum Xanthine Oxidase and Its Correlation with Antioxidant Status in Patients with Parkinson’s Disease
by
Ratna Dini Haryuni, Takamasa Nukui, Jin-Lan Piao, Takashi Shirakura, Chieko Matsui, Tomoyuki Sugimoto, Kousuke Baba, Shunya Nakane and Yuji Nakatsuji
Biomolecules 2024, 14(4), 490; https://doi.org/10.3390/biom14040490 - 18 Apr 2024
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at
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Parkinson’s disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged. Several studies reported that oxidative stress is a key modulator in the development of PD. This condition occurs due to excess reactive oxygen species (ROS) production in the cellular system and the incapability of antioxidants to neutralize it. In this study, we focused on the pathology of PD by measuring serum xanthine oxidase (XO) activity, which is an enzyme that generates ROS. Interestingly, the serum XO activity of patients with PD was markedly upregulated compared to patients with other neurological diseases (ONDs) as a control. Moreover, serum XO activity in patients with PD showed a significant correlation with the disease severity based on the Hoehn and Yahr (HY) stages. The investigation of antioxidant status also revealed that serum uric acid levels were significantly lower in the severe group (HY ≥ 3) than in the ONDs group. Together, these results suggest that XO activity may contribute to the development of PD and might potentially be a biomarker for determining disease severity in patients with PD.
Full article
(This article belongs to the Special Issue Advances in Biomarkers for Neurodegenerative Diseases)
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Open AccessReview
Thrombopoietin, the Primary Regulator of Platelet Production: From Mythos to Logos, a Thirty-Year Journey
by
Kenneth Kaushansky
Biomolecules 2024, 14(4), 489; https://doi.org/10.3390/biom14040489 - 18 Apr 2024
Abstract
Thrombopoietin, the primary regulator of blood platelet production, was postulated to exist in 1958, but was only proven to exist when the cDNA for the hormone was cloned in 1994. Since its initial cloning and characterization, the hormone has revealed many surprises. For
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Thrombopoietin, the primary regulator of blood platelet production, was postulated to exist in 1958, but was only proven to exist when the cDNA for the hormone was cloned in 1994. Since its initial cloning and characterization, the hormone has revealed many surprises. For example, instead of acting as the postulated differentiation factor for platelet precursors, megakaryocytes, it is the most potent stimulator of megakaryocyte progenitor expansion known. Moreover, it also stimulates the survival, and in combination with stem cell factor leads to the expansion of hematopoietic stem cells. All of these growth-promoting activities have resulted in its clinical use in patients with thrombocytopenia and aplastic anemia, although the clinical development of the native molecule illustrated that “it’s not wise to mess with mother nature”, as a highly engineered version of the native hormone led to autoantibody formation and severe thrombocytopenia. Finally, another unexpected finding was the role of the thrombopoietin receptor in stem cell biology, including the development of myeloproliferative neoplasms, an important disorder of hematopoietic stem cells. Overall, the past 30 years of clinical and basic research has yielded many important insights, which are reviewed in this paper.
Full article
(This article belongs to the Special Issue From the Past to the Present: Unveiling the Role of Biomolecules in Clinical History)
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Open AccessReview
Categorizing Extrachromosomal Circular DNA as Biomarkers in Serum of Cancer
by
Enze Deng and Xiaoying Fan
Biomolecules 2024, 14(4), 488; https://doi.org/10.3390/biom14040488 - 17 Apr 2024
Abstract
Extrachromosomal circular DNA (eccDNA), a double-stranded circular DNA molecule found in multiple organisms, has garnered an increasing amount of attention in recent years due to its close association with the initiation, malignant progression, and heterogeneous evolution of cancer. The presence of eccDNA in
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Extrachromosomal circular DNA (eccDNA), a double-stranded circular DNA molecule found in multiple organisms, has garnered an increasing amount of attention in recent years due to its close association with the initiation, malignant progression, and heterogeneous evolution of cancer. The presence of eccDNA in serum assists in non-invasive tumor diagnosis as a biomarker that can be assessed via liquid biopsies. Furthermore, the specific expression patterns of eccDNA provide new insights into personalized cancer therapy. EccDNA plays a pivotal role in tumorigenesis, development, diagnosis, and treatment. In this review, we comprehensively outline the research trajectory of eccDNA, discuss its role as a diagnostic and prognostic biomarker, and elucidate its regulatory mechanisms in cancer. In particular, we emphasize the potential application value of eccDNA in cancer diagnosis and treatment and anticipate the development of novel tumor diagnosis strategies based on serum eccDNA in the future.
Full article
(This article belongs to the Special Issue Recent Developments in the Biology of Extracellular or Cell-Free DNA)
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Open AccessArticle
In Silico Analysis of the Ga3+/Fe3+ Competition for Binding the Iron-Scavenging Siderophores of P. aeruginosa—Implementation of Three Gallium-Based Complexes in the “Trojan Horse” Antibacterial Strategy
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Nikoleta Kircheva, Stefan Dobrev, Vladislava Petkova, Lyubima Yocheva, Silvia Angelova and Todor Dudev
Biomolecules 2024, 14(4), 487; https://doi.org/10.3390/biom14040487 - 16 Apr 2024
Abstract
The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial
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The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe2+/3+-containing enzymes have been identified as a plausible target of great potential. The intriguing “Trojan horse” approach deprives microorganisms from the essential iron. Recently, gallium’s potential in medicine as an iron mimicry species has attracted vast attention. Different Ga3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa. Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO3)3, metabolized to Ga3+-hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream—the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga3+/Fe3+ rivalry for binding the two bacterial siderophores.
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(This article belongs to the Collection Feature Papers in Biochemistry)
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Open AccessCommunication
Application of Cas12j for Streptomyces Editing
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Lee Ling Tan, Elena Heng, Chung Yan Leong, Veronica Ng, Lay Kien Yang, Deborah Chwee San Seow, Lokanand Koduru, Yoganathan Kanagasundaram, Siew Bee Ng, Guangrong Peh, Yee Hwee Lim and Fong Tian Wong
Biomolecules 2024, 14(4), 486; https://doi.org/10.3390/biom14040486 - 16 Apr 2024
Abstract
In recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Streptococcus pyogenes Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety
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In recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Streptococcus pyogenes Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of Streptomyces strains. This study explored the first use of Acidaminococcus sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in Streptomyces and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previously reported efficiencies of Cas12a and Cas9, Cas12j exhibited higher transformation efficiencies compared to SpCas9. Furthermore, Cas12j demonstrated significantly improved editing efficiencies compared to Cas12a in activating BGCs in Streptomyces sp. A34053, a strain wherein both SpCas9 and Cas12a faced limitations in accessing the genome. Overall, this study expanded the repertoire of Cas proteins for genome editing in actinomycetes and highlighted not only the potential of recently characterized Cas12j in Streptomyces but also the importance of having an extensive genetic toolbox for improving the editing success of these beneficial microbes.
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(This article belongs to the Section Synthetic Biology and Bioengineering)
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Open AccessFeature PaperReview
Cell Senescence in Heterotopic Ossification
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Robert J. Pignolo, Frederick S. Kaplan and Haitao Wang
Biomolecules 2024, 14(4), 485; https://doi.org/10.3390/biom14040485 - 16 Apr 2024
Abstract
The formation of bone outside the normal skeleton, or heterotopic ossification (HO), occurs through genetic and acquired mechanisms. Fibrodysplasia ossificans progressiva (FOP), the most devastating genetic condition of HO, is due to mutations in the ACVR1/ALK2 gene and is relentlessly progressive. Acquired HO
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The formation of bone outside the normal skeleton, or heterotopic ossification (HO), occurs through genetic and acquired mechanisms. Fibrodysplasia ossificans progressiva (FOP), the most devastating genetic condition of HO, is due to mutations in the ACVR1/ALK2 gene and is relentlessly progressive. Acquired HO is mostly precipitated by injury or orthopedic surgical procedures but can also be associated with certain conditions related to aging. Cellular senescence is a hallmark of aging and thought to be a tumor-suppressive mechanism with characteristic features such as irreversible growth arrest, apoptosis resistance, and an inflammatory senescence-associated secretory phenotype (SASP). Here, we review possible roles for cellular senescence in HO and how targeting senescent cells may provide new therapeutic approaches to both FOP and acquired forms of HO.
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(This article belongs to the Section Molecular Medicine)
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Open AccessReview
Strategies for Treating Traumatic Neuromas with Tissue-Engineered Materials
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Teng Wan, Qi-Cheng Li, Ming-Yu Qin, Yi-Lin Wang, Feng-Shi Zhang, Xiao-Meng Zhang, Yi-Chong Zhang and Pei-Xun Zhang
Biomolecules 2024, 14(4), 484; https://doi.org/10.3390/biom14040484 - 16 Apr 2024
Abstract
Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include
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Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include surgical excision and pharmacological management, aiming to alleviate symptoms. However, these approaches often offer temporary relief without addressing the underlying regenerative challenges, necessitating the exploration of advanced strategies such as tissue-engineered materials for more comprehensive and effective solutions. In this study, we discussed the etiology, molecular mechanisms, and histological morphology of traumatic neuromas after peripheral nerve injury. Subsequently, we summarized and analyzed current nonsurgical and surgical treatment options, along with their advantages and disadvantages. Additionally, we emphasized recent advancements in treating traumatic neuromas with tissue-engineered material strategies. By integrating biomaterials, growth factors, cell-based approaches, and electrical stimulation, tissue engineering offers a comprehensive solution surpassing mere symptomatic relief, striving for the structural and functional restoration of damaged nerves. In conclusion, the utilization of tissue-engineered materials has the potential to significantly reduce the risk of neuroma recurrence after surgical treatment.
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(This article belongs to the Section Biological and Bio- Materials)
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Open AccessReview
Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis
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Yanqiu Peng, Lixia Zhao, Min Li, Yunfei Liu, Yuke Shi and Jian Zhang
Biomolecules 2024, 14(4), 483; https://doi.org/10.3390/biom14040483 (registering DOI) - 16 Apr 2024
Abstract
Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend the biological properties of different adipose tissue types and their respective roles in
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Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend the biological properties of different adipose tissue types and their respective roles in maintaining energy balance. Adipose tissue serves as a crucial organ for energy storage and metabolism in the human body, with functions extending beyond simple fat storage to encompass the regulation of energy homeostasis and the secretion of endocrine factors. This review provides an overview of the key characteristics, functional differences, and interconversion processes among white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. Moreover, it delves into the molecular mechanisms and recent research advancements concerning the browning of WAT, activation of BAT, and whitening of BAT. Although targeting adipose tissue metabolism holds promise as a potential approach for obesity treatment, further investigations are necessary to unravel the intricate biological features of various adipose tissue types and elucidate the molecular pathways governing their interconversion. Such research endeavors will pave the way for the development of more efficient and targeted therapeutic interventions in the fight against obesity.
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(This article belongs to the Section Biomacromolecules: Lipids)
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Open AccessArticle
Novel Organic–Inorganic Nanocomposite Hybrids Based on Bioactive Glass Nanoparticles and Their Enhanced Osteoinductive Properties
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Nicolás Cohn, Henrik Bradtmüller, Edgar Zanotto, Alfredo von Marttens and Cristian Covarrubias
Biomolecules 2024, 14(4), 482; https://doi.org/10.3390/biom14040482 - 16 Apr 2024
Abstract
Inorganic–organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first
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Inorganic–organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first time the synthesis of a class II hybrid modified with bioactive glass nanoparticles (nBGs) with osteoinductive properties. The nanocomposite hybrids were produced by incorporating nBGs in situ into a polytetrahydrofuran (PTHF) and silica (SiO2) hybrid synthesis mixture using a combined sol–gel and cationic polymerization method. nBGs ~80 nm in size were synthesized using the sol–gel technique. The structure, composition, morphology, and mechanical properties of the resulting materials were characterized using ATR-FTIR, 29Si MAS NMR, SEM-EDX, AFM, TGA, DSC, mechanical, and DMA testing. The in vitro bioactivity and degradability of the hybrids were assessed in simulated body fluid (SBF) and PBS, respectively. Cytocompatibility with mesenchymal stem cells was assessed using MTS and cell adhesion assays. Osteogenic differentiation was determined using the alkaline phosphatase activity (ALP), as well as the gene expression of Runx2 and Osterix markers. Hybrids loaded with 5, 10, and 15% of nBGs retained the mechanical flexibility of the PTHF–SiO2 matrix and improved its ability to promote the formation of bone-like apatite in SBF. The nBGs did not impair cell viability, increased the ALP activity, and upregulated the expression of Runx2 and Osterix. These results demonstrate that nBGs are an effective osteoinductive nanoadditive for the production of class II hybrid materials with enhanced properties for bone tissue regeneration.
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(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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Open AccessArticle
Oxidative Stress Reaction to Hypobaric–Hyperoxic Civilian Flight Conditions
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Nikolaus C. Netzer, Heidelinde Jaekel, Roland Popp, Johanna M. Gostner, Michael Decker, Frederik Eisendle, Rachel Turner, Petra Netzer, Carsten Patzelt, Christian Steurer, Marco Cavalli, Florian Forstner and Stephan Pramsohler
Biomolecules 2024, 14(4), 481; https://doi.org/10.3390/biom14040481 - 15 Apr 2024
Abstract
Background: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA)
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Background: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude. Aim: We hypothesized that hypobaric–hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals. Methods: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at −21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. Results: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude. Conclusion: Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m–4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.
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(This article belongs to the Special Issue Cell Differentiation, Oxidative Stress, and Oxygen Radicals—in Honor of Prof. Michael Breitenbach)
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Open AccessReview
Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy
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Shenghao Wang, Sikuan Gu, Junfan Chen, Zhiqiang Yuan, Ping Liang and Hongjuan Cui
Biomolecules 2024, 14(4), 480; https://doi.org/10.3390/biom14040480 - 15 Apr 2024
Abstract
Glioblastoma multiforme (GBM) is the most aggressive form of glioma and the most common primary tumor of the central nervous system. Despite significant advances in clinical management strategies and diagnostic techniques for GBM in recent years, it remains a fatal disease. The current
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Glioblastoma multiforme (GBM) is the most aggressive form of glioma and the most common primary tumor of the central nervous system. Despite significant advances in clinical management strategies and diagnostic techniques for GBM in recent years, it remains a fatal disease. The current standard of care includes surgery, radiation, and chemotherapy, but the five-year survival rate for patients is less than 5%. The search for a more precise diagnosis and earlier intervention remains a critical and urgent challenge in clinical practice. The Notch signaling pathway is a critical signaling system that has been extensively studied in the malignant progression of glioblastoma. This highly conserved signaling cascade is central to a variety of biological processes, including growth, proliferation, self-renewal, migration, apoptosis, and metabolism. In GBM, accumulating data suggest that the Notch signaling pathway is hyperactive and contributes to GBM initiation, progression, and treatment resistance. This review summarizes the biological functions and molecular mechanisms of the Notch signaling pathway in GBM, as well as some clinical advances targeting the Notch signaling pathway in cancer and glioblastoma, highlighting its potential as a focus for novel therapeutic strategies.
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(This article belongs to the Section Molecular Medicine)
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Open AccessReview
Advancements in the Application of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs)
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Sang-Woo Han and Hyung-Sik Won
Biomolecules 2024, 14(4), 479; https://doi.org/10.3390/biom14040479 - 15 Apr 2024
Abstract
Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a significant potential for novel therapeutic applications because of their bioactive properties, stability, and specificity. RiPPs are synthesized on ribosomes, followed by intricate post-translational modifications (PTMs), crucial for their diverse structures and functions. PTMs, such
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Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a significant potential for novel therapeutic applications because of their bioactive properties, stability, and specificity. RiPPs are synthesized on ribosomes, followed by intricate post-translational modifications (PTMs), crucial for their diverse structures and functions. PTMs, such as cyclization, methylation, and proteolysis, play crucial roles in enhancing RiPP stability and bioactivity. Advances in synthetic biology and bioinformatics have significantly advanced the field, introducing new methods for RiPP production and engineering. These methods encompass strategies for heterologous expression, genetic refactoring, and exploiting the substrate tolerance of tailoring enzymes to create novel RiPP analogs with improved or entirely new functions. Furthermore, the introduction and implementation of cutting-edge screening methods, including mRNA display, surface display, and two-hybrid systems, have expedited the identification of RiPPs with significant pharmaceutical potential. This comprehensive review not only discusses the current advancements in RiPP research but also the promising opportunities that leveraging these bioactive peptides for therapeutic applications presents, illustrating the synergy between traditional biochemistry and contemporary synthetic biology and genetic engineering approaches.
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(This article belongs to the Special Issue Development, Characterization, and Application of Bioactive Peptides, Diagnostic Biomarkers, and Pharmaceutical Proteins)
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Open AccessReview
Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective—A Narrative Review
by
Kenbon Beyene Abdisa, Emőke Szerdahelyi, Máté András Molnár, László Friedrich, Zoltán Lakner, András Koris, Attila Toth and Arijit Nath
Biomolecules 2024, 14(4), 478; https://doi.org/10.3390/biom14040478 - 14 Apr 2024
Abstract
Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of
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Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.
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(This article belongs to the Special Issue Nutrition, Metabolism, and Obesity: Novel Strategies and Molecular Mechanisms—Future Perspectives)
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Open AccessReview
Combined Pharmacological Modulation of Translational and Transcriptional Activity Signaling Pathways as a Promising Therapeutic Approach in Children with Myocardial Changes
by
Andrii Kamenshchyk, Igor Belenichev, Valentyn Oksenych and Oleksandr Kamyshnyi
Biomolecules 2024, 14(4), 477; https://doi.org/10.3390/biom14040477 - 13 Apr 2024
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Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This
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Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed the downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pumps, and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs make combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.
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Innate Immunity and MASLD
by
Moritz Meyer, Julian Schwärzler, Almina Jukic and Herbert Tilg
Biomolecules 2024, 14(4), 476; https://doi.org/10.3390/biom14040476 - 13 Apr 2024
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and
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Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.
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(This article belongs to the Special Issue Honorary Special Issue Dedicated to Prof. Giovanni Targher–the Metabolic Fatty Liver Syndromes: MASLD/MAFLD/NAFLD)
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Bactericidal Permeability-Increasing Protein (BPI) Inhibits Mycobacterium tuberculosis Growth
by
Silvia Guzmán-Beltrán, Esmeralda Juárez, Brenda L. Cruz-Muñoz, Cesar A. Páez-Cisneros, Carmen Sarabia and Yolanda González
Biomolecules 2024, 14(4), 475; https://doi.org/10.3390/biom14040475 - 13 Apr 2024
Abstract
Bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils, eosinophils, fibroblasts, and macrophages with antibacterial anti-inflammatory properties. In the context of Gram-negative infection, BPI kills bacteria, neutralizes the endotoxic activity of lipopolysaccharides (LPSs), and, thus, avoids immune hyperactivation. Interestingly, BPI
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Bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils, eosinophils, fibroblasts, and macrophages with antibacterial anti-inflammatory properties. In the context of Gram-negative infection, BPI kills bacteria, neutralizes the endotoxic activity of lipopolysaccharides (LPSs), and, thus, avoids immune hyperactivation. Interestingly, BPI increases in patients with Gram-positive meningitis, interacts with lipopeptides and lipoteichoic acids of Gram-positive bacteria, and significantly enhances the immune response in peripheral blood mononuclear cells. We evaluated the antimycobacterial and immunoregulatory properties of BPI in human macrophages infected with Mycobacterium tuberculosis. Our results showed that recombinant BPI entered macrophages, significantly reduced the intracellular growth of M. tuberculosis, and inhibited the production of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Furthermore, BPI decreased bacterial growth directly in vitro. These data suggest that BPI has direct and indirect bactericidal effects inhibiting bacterial growth and potentiating the immune response in human macrophages and support that this new protein’s broad-spectrum antibacterial activity has the potential for fighting tuberculosis.
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(This article belongs to the Special Issue Tuberculosis: Immunopathogenesis and Therapeutic Strategies)
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