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
ORAI Ca2+ Channels in Cancers and Therapeutic Interventions
Biomolecules 2024, 14(4), 417; https://doi.org/10.3390/biom14040417 - 29 Mar 2024
Abstract
The ORAI proteins serve as crucial pore-forming subunits of calcium-release-activated calcium (CRAC) channels, pivotal in regulating downstream calcium-related signaling pathways. Dysregulated calcium homeostasis arising from mutations and post-translational modifications in ORAI can lead to immune disorders, myopathy, cardiovascular diseases, and even cancers. Small
[...] Read more.
The ORAI proteins serve as crucial pore-forming subunits of calcium-release-activated calcium (CRAC) channels, pivotal in regulating downstream calcium-related signaling pathways. Dysregulated calcium homeostasis arising from mutations and post-translational modifications in ORAI can lead to immune disorders, myopathy, cardiovascular diseases, and even cancers. Small molecules targeting ORAI present an approach for calcium signaling modulation. Moreover, emerging techniques like optogenetics and optochemistry aim to offer more precise regulation of ORAI. This review focuses on the role of ORAI in cancers, providing a concise overview of their significance in the initiation and progression of cancers. Additionally, it highlights state-of-the-art techniques for ORAI channel modulation, including advanced optical tools, potent pharmacological inhibitors, and antibodies. These novel strategies offer promising avenues for the functional regulation of ORAI in research and may inspire innovative approaches to cancer therapy targeting ORAI.
Full article
(This article belongs to the Special Issue Role of STIM and Orai in Calcium Signaling)
►
Show Figures
Open AccessReview
Composition and Function of Neutrophil Extracellular Traps
by
Yijie Wang, Chunjing Du, Yue Zhang and Liuluan Zhu
Biomolecules 2024, 14(4), 416; https://doi.org/10.3390/biom14040416 (registering DOI) - 29 Mar 2024
Abstract
►▼
Show Figures
Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of depolymerized chromatin adorned with histones, granule proteins, and cytosolic proteins. NETs are formed via two distinct pathways known as suicidal NETosis, which
[...] Read more.
Neutrophil extracellular traps (NETs) are intricate fibrous structures released by neutrophils in response to specific stimuli. These structures are composed of depolymerized chromatin adorned with histones, granule proteins, and cytosolic proteins. NETs are formed via two distinct pathways known as suicidal NETosis, which involves NADPH oxidase (NOX), and vital NETosis, which is independent of NOX. Certain proteins found within NETs exhibit strong cytotoxic effects against both pathogens and nearby host cells. While NETs play a defensive role against pathogens, they can also contribute to tissue damage and worsen inflammation. Despite extensive research on the pathophysiological role of NETs, less attention has been paid to their components, which form a unique structure containing various proteins that have significant implications in a wide range of diseases. This review aims to elucidate the components of NETs and provide an overview of their impact on host defense against invasive pathogens, autoimmune diseases, and cancer.
Full article
Figure 1
Open AccessReview
Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia
by
Emanuele Marzetti, Biliana Lozanoska-Ochser, Riccardo Calvani, Francesco Landi, Hélio José Coelho-Júnior and Anna Picca
Biomolecules 2024, 14(4), 415; https://doi.org/10.3390/biom14040415 - 28 Mar 2024
Abstract
Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been
[...] Read more.
Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia–reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.
Full article
(This article belongs to the Special Issue Interface of Aging and Biomaterials II)
Open AccessArticle
Integrated Proteomics and Metabolomics of Safflower Petal Wilting and Seed Development
by
Delphine Vincent, Priyanka Reddy and Daniel Isenegger
Biomolecules 2024, 14(4), 414; https://doi.org/10.3390/biom14040414 - 28 Mar 2024
Abstract
Safflower (Carthamus tinctorius L.) is an ancient oilseed crop of interest due to its diversity of end-use industrial and food products. Proteomic and metabolomic profiling of its organs during seed development, which can provide further insights on seed quality attributes to assist
[...] Read more.
Safflower (Carthamus tinctorius L.) is an ancient oilseed crop of interest due to its diversity of end-use industrial and food products. Proteomic and metabolomic profiling of its organs during seed development, which can provide further insights on seed quality attributes to assist in variety and product development, has not yet been undertaken. In this study, an integrated proteome and metabolic analysis have shown a high complexity of lipophilic proteins and metabolites differentially expressed across organs and tissues during seed development and petal wilting. We demonstrated that these approaches successfully discriminated safflower reproductive organs and developmental stages with the identification of 2179 unique compounds and 3043 peptides matching 724 unique proteins. A comparison between cotyledon and husk tissues revealed the complementarity of using both technologies, with husks mostly featuring metabolites (99%), while cotyledons predominantly yielded peptides (90%). This provided a more complete picture of mechanisms discriminating the seed envelope from what it protected. Furthermore, we showed distinct molecular signatures of petal wilting and colour transition, seed growth, and maturation. We revealed the molecular makeup shift occurring during petal colour transition and wilting, as well as the importance of benzenoids, phenylpropanoids, flavonoids, and pigments. Finally, our study emphasizes that the biochemical mechanisms implicated in the growing and maturing of safflower seeds are complex and far-reaching, as evidenced by AraCyc, PaintOmics, and MetaboAnalyst mapping capabilities. This study provides a new resource for functional knowledge of safflower seed and potentially further enables the precision development of novel products and safflower varieties with biotechnology and molecular farming applications.
Full article
(This article belongs to the Special Issue Sowing the Seed to Ensure the Future of Plant Proteomics: Commemorative Issue in Honor of Dr. Dominique Job (1947–2022))
►▼
Show Figures
Figure 1
Open AccessArticle
Unlocking Potential: Low Bovine Serum Albumin Enhances the Chondrogenicity of Human Adipose-Derived Stromal Cells in Pellet Cultures
by
Isabel Casado-Losada, Melanie Acosta, Barbara Schädl, Eleni Priglinger, Susanne Wolbank and Sylvia Nürnberger
Biomolecules 2024, 14(4), 413; https://doi.org/10.3390/biom14040413 - 28 Mar 2024
Abstract
Bovine serum albumin (BSA) plays a crucial role in cell culture media, influencing cellular processes such as proliferation and differentiation. Although it is commonly included in chondrogenic differentiation media, its specific function remains unclear. This study explores the effect of different BSA concentrations
[...] Read more.
Bovine serum albumin (BSA) plays a crucial role in cell culture media, influencing cellular processes such as proliferation and differentiation. Although it is commonly included in chondrogenic differentiation media, its specific function remains unclear. This study explores the effect of different BSA concentrations on the chondrogenic differentiation of human adipose-derived stromal/stem cells (hASCs). hASC pellets from six donors were cultured under chondrogenic conditions with three BSA concentrations. Surprisingly, a lower BSA concentration led to enhanced chondrogenesis. The degree of this effect was donor-dependent, classifying them into two groups: (1) high responders, forming at least 35% larger, differentiated pellets with low BSA in comparison to high BSA; (2) low responders, which benefitted only slightly from low BSA doses with a decrease in pellet size and marginal differentiation, indicative of low intrinsic differentiation potential. In all cases, increased chondrogenesis was accompanied by hypertrophy under low BSA concentrations. To the best of our knowledge, this is the first study showing improved chondrogenicity and the tendency for hypertrophy with low BSA concentration compared to standard levels. Once the tendency for hypertrophy is understood, the determination of BSA concentration might be used to tune hASC chondrogenic or osteogenic differentiation.
Full article
(This article belongs to the Special Issue Biomolecules and Their Impact on Biology and Translational Applications: Celebrating the Pioneering Work of Prof. Ho Jeong Kwon)
►▼
Show Figures
Figure 1
Open AccessReview
The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases
by
Armando Rojas, Cristian Lindner, Ivan Schneider, Ileana Gonzalez and Jaime Uribarri
Biomolecules 2024, 14(4), 412; https://doi.org/10.3390/biom14040412 - 28 Mar 2024
Abstract
In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids
[...] Read more.
In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE’s role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands.
Full article
(This article belongs to the Special Issue Advanced Glycation End-Products (AGEs): Receptors, Signalling Pathways, and Anti-AGE Therapies)
►▼
Show Figures
Figure 1
Open AccessArticle
Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue
by
Sharon Natasha Cox, Claudio Lo Giudice, Anna Lavecchia, Maria Luana Poeta, Matteo Chiara, Ernesto Picardi and Graziano Pesole
Biomolecules 2024, 14(4), 411; https://doi.org/10.3390/biom14040411 - 28 Mar 2024
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the
[...] Read more.
Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS.
Full article
(This article belongs to the Special Issue Defects in the Transport Mechanism of Membrane Proteins and Related Diseases)
►▼
Show Figures
Figure 1
Open AccessReview
Chemical Inhibition of Sterol Biosynthesis
by
Eric S. Peeples, Karoly Mirnics and Zeljka Korade
Biomolecules 2024, 14(4), 410; https://doi.org/10.3390/biom14040410 - 28 Mar 2024
Abstract
►▼
Show Figures
Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications,
[...] Read more.
Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.
Full article
Figure 1
Open AccessReview
A Review for Artificial Intelligence Based Protein Subcellular Localization
by
Hanyu Xiao, Yijin Zou, Jieqiong Wang and Shibiao Wan
Biomolecules 2024, 14(4), 409; https://doi.org/10.3390/biom14040409 - 27 Mar 2024
Abstract
Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give
[...] Read more.
Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcellular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.
Full article
(This article belongs to the Special Issue Artificial Intelligence (AI) in Biomedicine)
►▼
Show Figures
Figure 1
Open AccessReview
Erythropoietin: A Personal Alice in Wonderland Trip in the Shadow of the Giants
by
Anna Rita Migliaccio
Biomolecules 2024, 14(4), 408; https://doi.org/10.3390/biom14040408 - 27 Mar 2024
Abstract
The identification of the hormone erythropoietin (EPO), which regulates red blood cell production, and its development into a pharmaceutical-grade product to treat anemia has been not only a herculean task but it has also been the first of its kind. As with all
[...] Read more.
The identification of the hormone erythropoietin (EPO), which regulates red blood cell production, and its development into a pharmaceutical-grade product to treat anemia has been not only a herculean task but it has also been the first of its kind. As with all the successes, it had “winners” and “losers”, but its history is mostly told by the winners who, over the years, have published excellent scientific and divulgate summaries on the subject, some of which are cited in this review. In addition, “success” is also due to the superb and dedicated work of numerous “crew” members, who often are under-represented and under-recognized when the story is told and often have several “dark sides” that are not told in the polished context of most reviews, but which raised the need for the development of the current legislation on biotherapeutics. Although I was marginally involved in the clinical development of erythropoietin, I have known on a personal basis most, if not all, the protagonists of the saga and had multiple opportunities to talk with them on the drive that supported their activities. Here, I will summarize the major steps in the development of erythropoietin as the first bioproduct to enter the clinic. Some of the “dark sides” will also be mentioned to emphasize what a beautiful achievement of humankind this process has been and how the various unforeseen challenges that emerged were progressively addressed in the interest of science and of the patient’s wellbeing.
Full article
(This article belongs to the Special Issue From the Past to the Present: Unveiling the Role of Biomolecules in Clinical History)
►▼
Show Figures
Figure 1
Open AccessCorrection
Correction: Liu et al. Emergent Peptides of the Antifibrotic Arsenal: Taking Aim at Myofibroblast Promoting Pathways. Biomolecules 2023, 13, 1179
by
Zhen Liu, Xinyan Zhang, Yanrong Wang, Yifan Tai, Xiaolin Yao and Adam C. Midgley
Biomolecules 2024, 14(4), 407; https://doi.org/10.3390/biom14040407 - 27 Mar 2024
Abstract
There was an error in the original publication [...]
Full article
Open AccessReview
Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular Ca2+ Homeostasis as a Rational Therapeutic Target in Leishmaniasis and Chagas Disease
by
Gustavo Benaim and Alberto Paniz-Mondolfi
Biomolecules 2024, 14(4), 406; https://doi.org/10.3390/biom14040406 - 27 Mar 2024
Abstract
Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American Trypanosomiasis (Chagas disease). Although its precise mechanisms are not yet fully
[...] Read more.
Originally developed as a chemotherapeutic agent, miltefosine (hexadecylphosphocholine) is an inhibitor of phosphatidylcholine synthesis with proven antiparasitic effects. It is the only oral drug approved for the treatment of Leishmaniasis and American Trypanosomiasis (Chagas disease). Although its precise mechanisms are not yet fully understood, miltefosine exhibits broad-spectrum anti-parasitic effects primarily by disrupting the intracellular Ca2+ homeostasis of the parasites while sparing the human hosts. In addition to its inhibitory effects on phosphatidylcholine synthesis and cytochrome c oxidase, miltefosine has been found to affect the unique giant mitochondria and the acidocalcisomes of parasites. Both of these crucial organelles are involved in Ca2+ regulation. Furthermore, miltefosine has the ability to activate a specific parasite Ca2+ channel that responds to sphingosine, which is different to its L-type VGCC human ortholog. Here, we aimed to provide an overview of recent advancements of the anti-parasitic mechanisms of miltefosine. We also explored its multiple molecular targets and investigated how its pleiotropic effects translate into a rational therapeutic approach for patients afflicted by Leishmaniasis and American Trypanosomiasis. Notably, miltefosine’s therapeutic effect extends beyond its impact on the parasite to also positively affect the host’s immune system. These findings enhance our understanding on its multi-targeted mechanism of action. Overall, this review sheds light on the intricate molecular actions of miltefosine, highlighting its potential as a promising therapeutic option against these debilitating parasitic diseases.
Full article
(This article belongs to the Special Issue Dysregulation of Calcium Signaling in Pathological Processes)
►▼
Show Figures
Figure 1
Open AccessArticle
The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells
by
Karen Libberecht, Nathalie Dirkx, Tim Vangansewinkel, Wendy Vandendries, Ivo Lambrichts and Esther Wolfs
Biomolecules 2024, 14(4), 405; https://doi.org/10.3390/biom14040405 - 27 Mar 2024
Abstract
Background: Dysregulation of the endo-lysosomal–autophagy pathway has been identified as a critical factor in the pathology of various demyelinating neurodegenerative diseases, including peripheral neuropathies. This pathway plays a crucial role in transporting newly synthesized myelin proteins to the plasma membrane in myelinating Schwann
[...] Read more.
Background: Dysregulation of the endo-lysosomal–autophagy pathway has been identified as a critical factor in the pathology of various demyelinating neurodegenerative diseases, including peripheral neuropathies. This pathway plays a crucial role in transporting newly synthesized myelin proteins to the plasma membrane in myelinating Schwann cells, making these cells susceptible to lysosome-related dysfunctions. Nevertheless, the specific impact of lysosomal dysfunction in Schwann cells and its contribution to neurodegeneration remain poorly understood. Methods: We aim to mimic lysosomal dysfunction in Schwann cells using chloroquine, a lysosomal dysfunction inducer, and to monitor lysosomal leakiness, Schwann cell viability, and apoptosis over time. Additionally, due to the ethical and experimental issues associated with cell isolation and the culturing of human Schwann cells, we use human dental pulp stem cell-derived Schwann cells (DPSC-SCs) as a model in our study. Results: Chloroquine incubation boosts lysosomal presence as demonstrated by an increased Lysotracker signal. Further in-depth lysosomal analysis demonstrated an increased lysosomal size and permeability as illustrated by a TEM analysis and GAL3-LAMP1 staining. Moreover, an Alamar blue assay and Caspase-3 staining demonstrates a reduced viability and increased apoptosis, respectively. Conclusions: Our data indicate that prolonged lysosomal dysfunction leads to lysosomal permeability, reduced viability, and eventually apoptosis in human DPSC-SCs.
Full article
(This article belongs to the Section Cellular Biochemistry)
►▼
Show Figures
Figure 1
Open AccessReview
Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression
by
Natalia A. Osna, Irina Tikhanovich, Martí Ortega-Ribera, Sebastian Mueller, Chaowen Zheng, Johannes Mueller, Siyuan Li, Sadatsugu Sakane, Raquel Carvalho Gontijo Weber, Hyun Young Kim, Wonseok Lee, Souradipta Ganguly, Yusuke Kimura, Xiao Liu, Debanjan Dhar, Karin Diggle, David A. Brenner, Tatiana Kisseleva, Neha Attal, Iain H. McKillop, Shilpa Chokshi, Ram Mahato, Karuna Rasineni, Gyongyi Szabo and Kusum K. Kharbandaadd
Show full author list
remove
Hide full author list
Biomolecules 2024, 14(4), 404; https://doi.org/10.3390/biom14040404 - 27 Mar 2024
Abstract
Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here,
[...] Read more.
Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.
Full article
(This article belongs to the Section Molecular Medicine)
►▼
Show Figures
Figure 1
Open AccessArticle
Dysbiosis of Gut Microbiome Aggravated Male Infertility in Captivity of Plateau Pika
by
Liangzhi Zhang, Xianjiang Tang, Chao Fan, Shi’en Ren, Qi Cheng, Huakun Zhou, Kai Liu, Shangang Jia and Yanming Zhang
Biomolecules 2024, 14(4), 403; https://doi.org/10.3390/biom14040403 - 26 Mar 2024
Abstract
Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and
[...] Read more.
Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial α-diversity and Firmicutes/Bacteroidetes ratio were drastically decreased in the captivity group. Bacteroidetes and Muribaculaceae abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites’ short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between Gastranaerophilales family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.
Full article
(This article belongs to the Collection Feature Papers in Molecular Reproduction)
►▼
Show Figures
Figure 1
Open AccessReview
Mitochondrial Dysfunction as the Major Basis of Brain Aging
by
Stephen C. Bondy
Biomolecules 2024, 14(4), 402; https://doi.org/10.3390/biom14040402 - 26 Mar 2024
Abstract
The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness
[...] Read more.
The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by the mitochondria in the transition of these three important processes toward more deleterious variants as brain aging proceeds. The immune system: the shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. Reactive oxygen species are important intracellular signaling systems. Additionally, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted, and persistent generation of pro-oxidant free radicals (oxidative stress). The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffused. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.
Full article
(This article belongs to the Collection Molecular Mechanisms of Obesity, Diabetes, Inflammation and Aging)
►▼
Show Figures
Figure 1
Open AccessReview
Multifactorial Causes and Consequences of TLSP Production, Function, and Release in the Asthmatic Airway
by
Danica L. Brister, Hafsa Omer, Christiane E. Whetstone, Maral Ranjbar and Gail M. Gauvreau
Biomolecules 2024, 14(4), 401; https://doi.org/10.3390/biom14040401 - 26 Mar 2024
Abstract
Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate
[...] Read more.
Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate to the inhaled trigger can exacerbate airway diseases such as asthma. Allergens inhaled into previously sensitized airways are known to drive a T2 inflammatory response through the polarization of T cells by dendritic cells mediated by TSLP. Harmful compounds found within air pollution, microbes, and viruses are also triggers causing airway epithelial cell release of TSLP in asthmatic airways. The release of TSLP leads to the development of inflammation which, when unchecked, can result in asthma exacerbations. Genetic and inheritable factors can contribute to the variable expression of TSLP and the risk and severity of asthma. This paper will review the various triggers and consequences of TSLP release in asthmatic airways.
Full article
(This article belongs to the Special Issue The Role of Epithelial Cells in Airway Diseases)
►▼
Show Figures
Figure 1
Open AccessReview
The Role of Citrullination Modification in CD4+ T Cells in the Pathogenesis of Immune-Related Diseases
by
Yuhang Chen, Yi Teng, Ping Xu and Shengjun Wang
Biomolecules 2024, 14(4), 400; https://doi.org/10.3390/biom14040400 - 26 Mar 2024
Abstract
►▼
Show Figures
The post-translational modifications (PTMs) of proteins play a crucial role in increasing the functional diversity of proteins and are associated with the pathogenesis of various diseases. This review focuses on a less explored PTM called citrullination, which involves the conversion of arginine to
[...] Read more.
The post-translational modifications (PTMs) of proteins play a crucial role in increasing the functional diversity of proteins and are associated with the pathogenesis of various diseases. This review focuses on a less explored PTM called citrullination, which involves the conversion of arginine to citrulline. This process is catalyzed by peptidyl arginine deiminases (PADs). Different members of the PAD family have distinct tissue distribution patterns and functions. Citrullination is a post-translational modification of native proteins that can alter their structure and convert them into autoantigens; thus, it mediates the occurrence of autoimmune diseases. CD4+ T cells, including Th1, Th2, and Th17 cells, are important immune cells involved in mediating autoimmune diseases, allergic reactions, and tumor immunity. PADs can induce citrullination in CD4+ T cells, suggesting a role for citrullination in CD4+ T cell subset differentiation and function. Understanding the role of citrullination in CD4+ T cells may provide insights into immune-related diseases and inflammatory processes.
Full article
Figure 1
Open AccessReview
Fragile X Messenger Ribonucleoprotein Protein and Its Multifunctionality: From Cytosol to Nucleolus and Back
by
Mohamed S. Taha and Mohammad Reza Ahmadian
Biomolecules 2024, 14(4), 399; https://doi.org/10.3390/biom14040399 - 26 Mar 2024
Abstract
Silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene and a consequent lack of FMR protein (FMRP) synthesis are associated with fragile X syndrome, one of the most common inherited intellectual disabilities. FMRP is a multifunctional protein that is involved
[...] Read more.
Silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene and a consequent lack of FMR protein (FMRP) synthesis are associated with fragile X syndrome, one of the most common inherited intellectual disabilities. FMRP is a multifunctional protein that is involved in many cellular functions in almost all subcellular compartments under both normal and cellular stress conditions in neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and it is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes the recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.
Full article
(This article belongs to the Section Biomacromolecules: Proteins)
►▼
Show Figures
Figure 1
Open AccessReview
Biomarkers for Managing Neurodegenerative Diseases
by
Lara Cheslow, Adam E. Snook and Scott A. Waldman
Biomolecules 2024, 14(4), 398; https://doi.org/10.3390/biom14040398 - 26 Mar 2024
Abstract
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies
[...] Read more.
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).
Full article
(This article belongs to the Special Issue Advances in Biomarkers for Neurodegenerative Diseases)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- Biomolecules Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomolecules, Cells, Genes, IJMS, ncRNA
MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume
Topic Editors: Y-h. Taguchi, Hsiuying WangDeadline: 20 April 2024
Topic in
Bioengineering, Biomolecules, Cancers, Diseases, Nanomaterials, Pharmaceutics
Dynamic Nano-Biomaterials in Tissue Regeneration and Cancer Therapies
Topic Editors: Ramar Thangam, Heemin Kang, Bibin G. Anand, Ramachandran Vijayan, Venugopal KrishnanDeadline: 15 May 2024
Topic in
Analytica, Biomolecules, Metabolites, Molecules, Separations
Advances in Separation Methods for Metabolomics and Lipidomics
Topic Editors: Eduardo Sommella, Giulia Mazzoccanti, Emanuela SalviatiDeadline: 31 May 2024
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Conferences
Special Issues
Special Issue in
Biomolecules
Molecular Mechanisms of Alpha-Synuclein in Parkinson's Disease and Other Synucleinopathies
Guest Editors: Iván Martínez-Valbuena, Diego Santos-García, Felix Javier Jiménez JiménezDeadline: 30 March 2024
Special Issue in
Biomolecules
Recent Advances in Proteogenomics
Guest Editor: Masaaki OyamaDeadline: 31 March 2024
Special Issue in
Biomolecules
Molecular Plant Reproduction: From Cells to Nature
Guest Editor: Diego HojsgaardDeadline: 15 April 2024
Special Issue in
Biomolecules
PPARs as Key Regulators in Different Diseases
Guest Editors: Davide Capelli, Roberta MontanariDeadline: 30 April 2024
Topical Collections
Topical Collection in
Biomolecules
Feature Papers in Molecular Genetics
Collection Editor: Jürg Bähler
Topical Collection in
Biomolecules
Feature Papers in Bioinformatics and Systems Biology Section
Collection Editor: Lukasz Kurgan
Topical Collection in
Biomolecules
Molecular Mechanisms of Obesity, Diabetes, Inflammation and Aging
Collection Editors: Susanne Talcott, Yuxiang Sun