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
The Improved Antineoplastic Activity of Thermophilic L-Asparaginase Tli10209 via Site-Directed Mutagenesis
Biomolecules 2024, 14(6), 686; https://doi.org/10.3390/biom14060686 (registering DOI) - 12 Jun 2024
Abstract
Amino acid deprivation therapy (AADT) is a novel anticancer therapy, considered nontoxic and selective. Thermophilic L-asparaginase enzymes display high stability and activity at elevated temperatures. However, they are of limited use in clinical applications because of their low substrate affinity and reduced activity
[...] Read more.
Amino acid deprivation therapy (AADT) is a novel anticancer therapy, considered nontoxic and selective. Thermophilic L-asparaginase enzymes display high stability and activity at elevated temperatures. However, they are of limited use in clinical applications because of their low substrate affinity and reduced activity under physiological conditions, which may necessitate an improved dosage, leading to side effects and greater costs. Thus, in an attempt to improve the activity of L-Asn at 37 °C, with the use of a semi-rational design, eight active-site mutants of Thermococcus litoralis DSM 5473 L-asparaginase Tli10209 were developed. T70A exhibited a 5.11-fold increase compared with the wild enzyme in physiological conditions. Double-mutant enzymes were created by combining mutants with higher hydrolysis activity. T70A/F36Y, T70A/K48L, and T70A/D50G were enhanced by 5.59-, 6.38-, and 5.58-fold. The immobilized enzyme applied in MCF-7 breast cancer cells only required one-seventh of the dose of the free enzyme to achieve the same inhibition rate under near-infrared irradiation. This provides a proof of concept that it is possible to reduce the consumption of L-Asn by improving its activity, thus providing a method to manage side effects.
Full article
(This article belongs to the Section Biomacromolecules: Proteins)
Open AccessReview
pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization
by
Pengyuan Dai, Meng Zou, Ziyi Cai, Xuhui Zeng, Xiaoning Zhang and Min Liang
Biomolecules 2024, 14(6), 685; https://doi.org/10.3390/biom14060685 (registering DOI) - 12 Jun 2024
Abstract
►▼
Show Figures
pH homeostasis is crucial for spermatogenesis, sperm maturation, sperm physiological function, and fertilization in mammals. HCO3− and H+ are the most significant factors involved in regulating pH homeostasis in the male reproductive system. Multiple pH-regulating transporters and ion channels localize
[...] Read more.
pH homeostasis is crucial for spermatogenesis, sperm maturation, sperm physiological function, and fertilization in mammals. HCO3− and H+ are the most significant factors involved in regulating pH homeostasis in the male reproductive system. Multiple pH-regulating transporters and ion channels localize in the testis, epididymis, and spermatozoa, such as HCO3− transporters (solute carrier family 4 and solute carrier family 26 transporters), carbonic anhydrases, and H+-transport channels and enzymes (e.g., Na+-H+ exchangers, monocarboxylate transporters, H+-ATPases, and voltage-gated proton channels). Hormone-mediated signals impose an influence on the production of some HCO3− or H+ transporters, such as NBCe1, SLC4A2, MCT4, etc. Additionally, ion channels including sperm-specific cationic channels for Ca2+ (CatSper) and K+ (SLO3) are directly or indirectly regulated by pH, exerting specific actions on spermatozoa. The slightly alkaline testicular pH is conducive to spermatogenesis, whereas the epididymis’s low HCO3− concentration and acidic lumen are favorable for sperm maturation and storage. Spermatozoa pH increases substantially after being fused with seminal fluid to enhance motility. In the female reproductive tract, sperm are subjected to increasing concentrations of HCO3− in the uterine and fallopian tube, causing a rise in the intracellular pH (pHi) of spermatozoa, leading to hyperpolarization of sperm plasma membranes, capacitation, hyperactivation, acrosome reaction, and ultimately fertilization. The physiological regulation initiated by SLC26A3, SLC26A8, NHA1, sNHE, and CFTR localized in sperm is proven for certain to be involved in male fertility. This review intends to present the key factors and characteristics of pHi regulation in the testes, efferent duct, epididymis, seminal fluid, and female reproductive tract, as well as the associated mechanisms during the sperm journey to fertilization, proposing insights into outstanding subjects and future research trends.
Full article
Figure 1
Open AccessReview
The Long Journey from Animal Electricity to the Discovery of Ion Channels and the Modelling of the Human Brain
by
Luigi Catacuzzeno, Antonio Michelucci and Fabio Franciolini
Biomolecules 2024, 14(6), 684; https://doi.org/10.3390/biom14060684 (registering DOI) - 12 Jun 2024
Abstract
This retrospective begins with Galvani’s experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions to the field of physical chemistry in the second half of the 19th century
[...] Read more.
This retrospective begins with Galvani’s experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions to the field of physical chemistry in the second half of the 19th century (Nernst’s equilibrium potential, based on the work of Wilhelm Ostwald, Max Planck’s ion electrodiffusion, Einstein’s studies of Brownian motion) which led Bernstein to propose his membrane theory in the early 1900s as an explanation of Galvani’s findings and cell excitability. These processes were fully elucidated by Hodgkin and Huxley in 1952 who detailed the ionic basis of resting and action potentials, but without addressing the question of where these ions passed. The emerging question of the existence of ion channels, widely debated over the next two decades, was finally accepted and, a decade later, many of them began to be cloned. This led to the possibility of modelling the activity of individual neurons in the brain and then that of simple circuits. Taking advantage of the remarkable advances in computer science in the new millennium, together with a much deeper understanding of brain architecture, more ambitious scientific goals were dreamed of to understand the brain and how it works. The retrospective concludes by reviewing the main efforts in this direction, namely the construction of a digital brain, an in silico copy of the brain that would run on supercomputers and behave just like a real brain.
Full article
(This article belongs to the Section Molecular Biophysics)
►▼
Show Figures
Figure 1
Open AccessReview
Unraveling the Immune Regulatory Functions of USP5: Implications for Disease Therapy
by
Jinyi Gu, Changshun Chen, Pu He, Yunjie Du and Bingdong Zhu
Biomolecules 2024, 14(6), 683; https://doi.org/10.3390/biom14060683 (registering DOI) - 12 Jun 2024
Abstract
Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins
[...] Read more.
Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. In the process of immune regulation, USP5 affects important cellular signaling pathways, such as NF-κB, Wnt/β-catenin, and IFN, by regulating ubiquitin-dependent protein degradation. These pathways play important roles in immune regulation and inflammatory responses. In addition, USP5 regulates the activity and function of immunomodulatory signaling pathways via the deubiquitination of key proteins, thereby affecting the activity of immune cells and the regulation of immune responses. In the present review, the structure and function of USP5, its role in immune regulation, and the mechanism by which USP5 affects the development of diseases by regulating immune signaling pathways are comprehensively overviewed. In addition, we also introduce the latest research progress of targeting USP5 in the treatment of related diseases, calling for an interdisciplinary approach to explore the therapeutic potential of targeting USP5 in immune regulation.
Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
►▼
Show Figures
Figure 1
Open AccessArticle
Integration of Proteomic and Metabolomic Data Reveals the Lipid Metabolism Disorder in the Liver of Rats Exposed to Simulated Microgravity
by
Mengyao Ru, Jun He, Yungang Bai, Kun Zhang, Qianqian Shi, Fang Gao, Yunying Wang, Baoli Li and Lan Shen
Biomolecules 2024, 14(6), 682; https://doi.org/10.3390/biom14060682 (registering DOI) - 12 Jun 2024
Abstract
Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based
[...] Read more.
Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography–tandem mass spectrometry (LC–MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.
Full article
(This article belongs to the Special Issue Effects of Weightlessness on Molecular Changes in Cellular Organisms, Animals and Plants)
►▼
Show Figures
Figure 1
Open AccessArticle
Repair and DNA Polymerase Bypass of Clickable Pyrimidine Nucleotides
by
Anton V. Endutkin, Anna V. Yudkina, Timofey D. Zharkov, Alexander E. Barmatov, Daria V. Petrova, Daria V. Kim and Dmitry O. Zharkov
Biomolecules 2024, 14(6), 681; https://doi.org/10.3390/biom14060681 - 12 Jun 2024
Abstract
Clickable nucleosides, most often 5-ethynyl-2′-deoxyuridine (EtU), are widely used in studies of DNA replication in living cells and in DNA functionalization for bionanotechology applications. Although clickable dNTPs are easily incorporated by DNA polymerases into the growing chain, afterwards they might become targets for
[...] Read more.
Clickable nucleosides, most often 5-ethynyl-2′-deoxyuridine (EtU), are widely used in studies of DNA replication in living cells and in DNA functionalization for bionanotechology applications. Although clickable dNTPs are easily incorporated by DNA polymerases into the growing chain, afterwards they might become targets for DNA repair systems or interfere with faithful nucleotide insertion. Little is known about the possibility and mechanisms of these post-synthetic events. Here, we investigated the repair and (mis)coding properties of EtU and two bulkier clickable pyrimidine nucleosides, 5-(octa-1,7-diyn-1-yl)-U (C8-AlkU) and 5-(octa-1,7-diyn-1-yl)-C (C8-AlkC). In vitro, EtU and C8-AlkU, but not C8-AlkC, were excised by SMUG1 and MBD4, two DNA glycosylases from the base excision repair pathway. However, when placed into a plasmid encoding a fluorescent reporter inactivated by repair in human cells, EtU and C8-AlkU persisted for much longer than uracil or its poorly repairable phosphorothioate-flanked derivative. DNA polymerases from four different structural families preferentially bypassed EtU, C8-AlkU and C8-AlkC in an error-free manner, but a certain degree of misincorporation was also observed, especially evident for DNA polymerase β. Overall, clickable pyrimidine nucleotides could undergo repair and be a source of mutations, but the frequency of such events in the cell is unlikely to be considerable.
Full article
(This article belongs to the Section Chemical Biology)
►▼
Show Figures
Figure 1
Open AccessReview
Translational Medicine in Acute Ischemic Stroke and Traumatic Brain Injury—NeuroAiD Trials, from Traditional Beliefs to Evidence-Based Therapy
by
Narayanaswamy Venketasubramanian, Tseng Tsai Yeo and Christopher Li Hsian Chen
Biomolecules 2024, 14(6), 680; https://doi.org/10.3390/biom14060680 - 11 Jun 2024
Abstract
►▼
Show Figures
Acute ischemic stroke (AIS) and traumatic brain injury (TBI) are two severe neurological events, both being major causes of death and prolonged impairment. Their incidence continues to rise due to the global increase in the number of people at risk, representing a significant
[...] Read more.
Acute ischemic stroke (AIS) and traumatic brain injury (TBI) are two severe neurological events, both being major causes of death and prolonged impairment. Their incidence continues to rise due to the global increase in the number of people at risk, representing a significant burden on those remaining impaired, their families, and society. These molecular and cellular mechanisms of both stroke and TBI present similarities that can be targeted by treatments with a multimodal mode of action, such as traditional Chinese medicine. Therefore, we performed a detailed review of the preclinical and clinical development of MLC901 (NeuroAiDTMII), a natural multi-herbal formulation targeting several biological pathways at the origin of the clinical deficits. The endogenous neurobiological processes of self-repair initiated by the brain in response to the onset of brain injury are often insufficient to achieve complete recovery of impaired functions. This review of MLC901 and its parent formulation MLC601 confirms that it amplifies the natural self-repair process of brain tissue after AIS or TBI. Following AIS and TBI where "time is brain", many patients enter the post-acute phase with their functions still impaired, a period when "the brain needs time to repair itself". The treatment goal must be to accelerate recovery as much as possible. MLC901/601 demonstrated a significant reduction by 18 months of recovery time compared to a placebo, indicating strong potential for facilitating the improvement of health outcomes and the more efficient use of healthcare resources.
Full article
Figure 1
Open AccessArticle
New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics
by
Milena Mlakić, Tena Čadež, Goran Šinko, Irena Škorić and Zrinka Kovarik
Biomolecules 2024, 14(6), 679; https://doi.org/10.3390/biom14060679 - 11 Jun 2024
Abstract
New furan, thiophene, and triazole oximes were synthesized through several-step reaction paths to investigate their potential for the development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Treating patients with acute OP poisoning is still a challenge despite
[...] Read more.
New furan, thiophene, and triazole oximes were synthesized through several-step reaction paths to investigate their potential for the development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Treating patients with acute OP poisoning is still a challenge despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, is blocked by OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to a cholinergic crisis. The oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper, we described the synthesis of 63 heterostilbene derivatives, of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents–sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in the micromolar range, we identified several oximes as BChE or AChE selective inhibitors with the potential for drug development. Furthermore, the oximes were poor reactivators of AChE; four heterocyclic derivatives reactivated cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had a reactivation efficacy comparable to the standard oxime HI-6. In silico analysis and molecular docking studies, including molecular dynamics simulation, connected kinetic data to the structural features of these oximes and confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Full article
(This article belongs to the Special Issue The Role of Cholinesterases in Alzheimer’s Disease and Other Neurodegenerative Disorders)
►▼
Show Figures
Figure 1
Open AccessArticle
Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage
by
Shaik Ismail Mohammed Thangameeran, Sheng-Tzung Tsai, Hock-Kean Liew and Cheng-Yoong Pang
Biomolecules 2024, 14(6), 678; https://doi.org/10.3390/biom14060678 - 11 Jun 2024
Abstract
Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis,
[...] Read more.
Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
Full article
(This article belongs to the Special Issue Intracerebral Hemorrhage: Advances in Preclinical Studies 2.0)
►▼
Show Figures
Figure 1
Open AccessArticle
Multi-Omics Insights into Disulfidptosis-Related Genes Reveal RPN1 as a Therapeutic Target for Liver Cancer
by
Yan He, Yue Hu, Yunsheng Cheng, Xutong Li, Chuanhong Chen, Shijie Zhang, Huihu He and Feng Cao
Biomolecules 2024, 14(6), 677; https://doi.org/10.3390/biom14060677 - 10 Jun 2024
Abstract
►▼
Show Figures
Disulfidptosis, a newly identified mode of programmed cell death, is yet to be comprehensively elucidated with respect to its multi-omics characteristics in tumors, specific pathogenic mechanisms, and antitumor functions in liver cancer. This study included 10,327 tumor and normal tissue samples from 33
[...] Read more.
Disulfidptosis, a newly identified mode of programmed cell death, is yet to be comprehensively elucidated with respect to its multi-omics characteristics in tumors, specific pathogenic mechanisms, and antitumor functions in liver cancer. This study included 10,327 tumor and normal tissue samples from 33 cancer types. In-depth analyses using various bioinformatics tools revealed widespread dysregulation of disulfidptosis-related genes (DRGs) in pan-cancer and significant associations with prognosis, genetic variations, tumor stemness, methylation levels, and drug sensitivity. Univariate and multivariate Cox regression and LASSO regression were used to screen and construct prognosis-related hub DRGs and predictive models in the context of liver cancer. Subsequently, single cell analysis was conducted to investigate the subcellular localization of RPN1, a hub DRG, in various solid tumors. Western blotting was performed to validate the expression of RPN1 at both cellular and tissue levels. Additionally, functional experiments, including CCK8, EdU, clone, and transwell assays, indicated that RPN1 knockdown promoted the proliferative and invasive capacities of liver cancer cells. Therefore, this study elucidated the multi-omics characteristics of DRGs in pan-cancer and established a prognostic model for liver cancer. Additionally, this study revealed the molecular functions of RPN1 in liver cancer, suggesting its potential as a therapeutic target for this disease.
Full article
Graphical abstract
Open AccessReview
Role of Secretory Mucins in the Occurrence and Development of Cholelithiasis
by
Zeying Zhao, Ye Yang, Shuodong Wu and Dianbo Yao
Biomolecules 2024, 14(6), 676; https://doi.org/10.3390/biom14060676 - 10 Jun 2024
Abstract
►▼
Show Figures
Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity,
[...] Read more.
Cholelithiasis is a common biliary tract disease. However, the exact mechanism underlying gallstone formation remains unclear. Mucin plays a vital role in the nuclear formation and growth of cholesterol and pigment stones. Excessive mucin secretion can result in cholestasis and decreased gallbladder activity, further facilitating stone formation and growth. Moreover, gallstones may result in inflammation and the secretion of inflammatory factors, which can further increase mucin expression and secretion to promote the growth of gallstones. This review systematically summarises and analyses the role of mucins in gallstone occurrence and development and its related mechanisms to explore new ideas for interventions in stone formation or recurrence.
Full article
Figure 1
Open AccessArticle
Perimenopause Decreases SERCA2a Activity in the Hearts of a Mouse Model of Ovarian Failure
by
Ciara Barry, Sarah Rouhana, Jessica L. Braun, Mia S. Geromella, Val A. Fajardo and W. Glen Pyle
Biomolecules 2024, 14(6), 675; https://doi.org/10.3390/biom14060675 - 9 Jun 2024
Abstract
Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized
[...] Read more.
Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction. Using a mouse model of menopause in which ovarian failure occurs over 120 days, we sought to determine if perimenopause impacted calcium removal mechanisms in the heart and identify the molecular mechanisms. Mice were injected with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure over 120 days, mimicking perimenopause. Hearts were removed at 60 and 120 days after VCD injections, representing the middle and end of perimenopause. SERCA2a function was significantly diminished at the end of perimenopause. Neither SERCA2a nor phospholamban expression changed at either time point, but phospholamban phosphorylation at S16 and T17 was dynamically altered. Intrinsic SERCA inhibitors sarcolipin and myoregulin increased >4-fold at day 60, as did the native activator DWORF. At the end of perimenopause, sarcolipin and myoregulin returned to baseline levels while DWORF was significantly reduced below controls. Sodium–calcium exchanger expression was significantly increased at the end of perimenopause. These results show that the foundation for increased cardiovascular disease mortality develops in the heart during perimenopause and that regulators of calcium handling exhibit significant fluctuations over time. Understanding the temporal development of cardiovascular risk associated with menopause and the underlying mechanisms is critical to developing interventions that mitigate the rise in cardiovascular mortality that arises after menopause.
Full article
(This article belongs to the Special Issue Heart Diseases: Molecular Mechanisms and New Therapies)
►▼
Show Figures
Figure 1
Open AccessArticle
Accurate Identification of Spatial Domain by Incorporating Global Spatial Proximity and Local Expression Proximity
by
Yuanyuan Yu, Yao He and Zhi Xie
Biomolecules 2024, 14(6), 674; https://doi.org/10.3390/biom14060674 - 9 Jun 2024
Abstract
Accurate identification of spatial domains is essential in the analysis of spatial transcriptomics data in order to elucidate tissue microenvironments and biological functions. However, existing methods only perform domain segmentation based on local or global spatial relationships between spots, resulting in an underutilization
[...] Read more.
Accurate identification of spatial domains is essential in the analysis of spatial transcriptomics data in order to elucidate tissue microenvironments and biological functions. However, existing methods only perform domain segmentation based on local or global spatial relationships between spots, resulting in an underutilization of spatial information. To this end, we propose SECE, a deep learning-based method that captures both local and global relationships among spots and aggregates their information using expression similarity and spatial similarity. We benchmarked SECE against eight state-of-the-art methods on six real spatial transcriptomics datasets spanning four different platforms. SECE consistently outperformed other methods in spatial domain identification accuracy. Moreover, SECE produced spatial embeddings that exhibited clearer patterns in low-dimensional visualizations and facilitated a more accurate trajectory inference.
Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
►▼
Show Figures
Figure 1
Open AccessReview
Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model
by
Sandro Huenchuguala and Juan Segura-Aguilar
Biomolecules 2024, 14(6), 673; https://doi.org/10.3390/biom14060673 - 8 Jun 2024
Abstract
One of the biggest problems in the treatment of idiopathic Parkinson’s disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical
[...] Read more.
One of the biggest problems in the treatment of idiopathic Parkinson’s disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for idiopathic Parkinson’s disease that requires years to accumulate enough lost neurons for the onset of motor symptoms. This single-neuron degeneration model is based on the excessive formation of aminochrome during neuromelanin synthesis that surpass the neuroprotective action of the enzymes DT-diaphorase and glutathione transferase M2-2, which prevent the neurotoxic effects of aminochrome. Although the neurotoxic effects of aminochrome do not have an expansive effect, a stereotaxic injection of this endogenous neurotoxin cannot be used to generate a preclinical model in an animal. Therefore, the aim of this review is to evaluate the strategies for pharmacologically increasing the expression of DT diaphorase and GSTM2-2 and molecules that induce the expression of vesicular monoamine transporter 2, such as pramipexole.
Full article
(This article belongs to the Special Issue The Multiple Roles of Glutathione-Dependent Enzymes: A Themed Issue in Honor of Prof. Bengt Mannervik)
►▼
Show Figures
Graphical abstract
Open AccessArticle
Anti-Inflammatory Responses Produced with Nippostrongylus brasiliensis-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model
by
Yingshu Zhang, Xin Ding, Caiyi Yuan, Yougui Yang, Qiang Zhang, Jiakai Yao, Ying Zhang, Junhong Wang and Yang Dai
Biomolecules 2024, 14(6), 672; https://doi.org/10.3390/biom14060672 - 8 Jun 2024
Abstract
►▼
Show Figures
Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that Nippostrongylus brasiliensis (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites
[...] Read more.
Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that Nippostrongylus brasiliensis (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites with anti-inflammation activity and evaluated the AS-prevention effect. We observed that the metabolite uridine had higher expression levels in mice infected with the Nb and ES (excretory–secretory) products and could be selected as a key metabolite. ES and uridine interventions could reduce the pro-inflammatory responses and increase the anti-inflammatory responses in vitro and in vivo. The apolipoprotein E gene knockout (ApoE−/−) mice were fed with a high-fat diet for the AS modeling. Following the in vivo intervention, ES products or uridine significantly reduced serum and liver lipid levels, alleviated the formation of atherosclerosis, and reduced the pro-inflammatory responses in serum or plaques, while the anti-inflammatory responses showed opposite trends. After blocking with 5-HD (5-hydroxydecanoate sodium) in vitro, the mRNA levels of M2 markers were significantly reduced. When blocked with 5-HD in vivo, the degree of atherosclerosis was worsened, the pro-inflammatory responses were increased compared to the uridine group, while the anti-inflammatory responses decreased accordingly. Uridine, a key metabolite from Nippostrongylus brasiliensis, showed anti-inflammatory and anti-atherosclerotic effects in vitro and in vivo, which depend on the activation of the mitochondrial ATP-sensitive potassium channel.
Full article
Graphical abstract
Open AccessArticle
Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation
by
Jiamin Fu, Qi Zhang, Ning Zhang, Sining Zhou, Yangxin Fang, Yifei Li, Li Yuan, Lijun Chen and Charlie Xiang
Biomolecules 2024, 14(6), 671; https://doi.org/10.3390/biom14060671 - 8 Jun 2024
Abstract
Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes.
[...] Read more.
Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine β-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using β-cell lines (MIN6, β-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of β-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.
Full article
Open AccessReview
Mitochondrial Reactive Oxygen Species in Infection and Immunity
by
Arunima Mukherjee, Krishna Kanta Ghosh, Sabyasachi Chakrabortty, Balázs Gulyás, Parasuraman Padmanabhan and Writoban Basu Ball
Biomolecules 2024, 14(6), 670; https://doi.org/10.3390/biom14060670 - 8 Jun 2024
Abstract
Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including
[...] Read more.
Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including ultra-violet (UV) radiation, electron leakage during aerobic respiration, inflammatory responses mediated by macrophages, and other external stimuli or stress. The enhanced production of ROS is termed oxidative stress and this leads to cellular damage, such as protein carbonylation, lipid peroxidation, deoxyribonucleic acid (DNA) damage, and base modifications. This damage may manifest in various pathological states, including ageing, cancer, neurological diseases, and metabolic disorders like diabetes. On the other hand, the optimum levels of ROS have been implicated in the regulation of many important physiological processes. For example, the ROS generated in the mitochondria (mitochondrial ROS or mt-ROS), as a byproduct of the electron transport chain (ETC), participate in a plethora of physiological functions, which include ageing, cell growth, cell proliferation, and immune response and regulation. In this current review, we will focus on the mechanisms by which mt-ROS regulate different pathways of host immune responses in the context of infection by bacteria, protozoan parasites, viruses, and fungi. We will also discuss how these pathogens, in turn, modulate mt-ROS to evade host immunity. We will conclude by briefly giving an overview of the potential therapeutic approaches involving mt-ROS in infectious diseases.
Full article
(This article belongs to the Special Issue Mitochondrial ROS in Health and Disease)
Open AccessReview
Molecular Genetics of Acquired Temporal Lobe Epilepsy
by
Anne-Marie Neumann and Stefan Britsch
Biomolecules 2024, 14(6), 669; https://doi.org/10.3390/biom14060669 - 7 Jun 2024
Abstract
An epilepsy diagnosis reduces a patient’s quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma
[...] Read more.
An epilepsy diagnosis reduces a patient’s quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop its manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize the current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss the major molecular pathways involved, with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasized the role of the genetic background for the acquisition of epilepsy, including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase the vulnerability of the hippocampus to develop epilepsy following an injury—an emerging perspective on the epileptogenic process in acquired forms of epilepsy.
Full article
(This article belongs to the Special Issue New Insight into the Molecular Genetics of Neurodevelopmental Disorders)
Open AccessReview
Unveiling the Druggable Landscape of Bacterial Peptidyl tRNA Hydrolase: Insights into Structure, Function, and Therapeutic Potential
by
Surbhi Mundra and Ashish Kabra
Biomolecules 2024, 14(6), 668; https://doi.org/10.3390/biom14060668 - 7 Jun 2024
Abstract
Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital
[...] Read more.
Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital for bacterial cells and an emerging drug target for various bacterial infections. Understanding the enzymatic mechanisms and structural intricacies of bacterial Pth is pivotal in designing novel therapeutics to combat antibiotic resistance. This review provides a comprehensive analysis of the multifaceted roles of Pth in bacterial physiology, shedding light on its significance as a potential drug target. This article delves into the diverse functions of Pth, encompassing its involvement in ribosome rescue, the maintenance of a free tRNA pool in bacterial systems, the regulation of translation fidelity, and stress response pathways within bacterial systems. Moreover, it also explores the druggability of bacterial Pth, emphasizing its promise as a target for antibacterial agents and highlighting the challenges associated with developing specific inhibitors against this enzyme. Structural elucidation represents a cornerstone in unraveling the catalytic mechanisms and substrate recognition of Pth. This review encapsulates the current structural insights of Pth garnered through various biophysical techniques, such as X-ray crystallography and NMR spectroscopy, providing a detailed understanding of the enzyme’s architecture and conformational dynamics. Additionally, biophysical aspects, including its interaction with ligands, inhibitors, and substrates, are discussed, elucidating the molecular basis of bacterial Pth’s function and its potential use in drug design strategies. Through this review article, we aim to put together all the available information on bacterial Pth and emphasize its potential in advancing innovative therapeutic interventions and combating bacterial infections.
Full article
(This article belongs to the Special Issue The Structure and Function of Proteins, Lipids and Nucleic Acids)
►▼
Show Figures
Figure 1
Open AccessReview
Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head
by
Jie Zhang, Jianze Cao, Yongfei Liu and Haiyan Zhao
Biomolecules 2024, 14(6), 667; https://doi.org/10.3390/biom14060667 - 6 Jun 2024
Abstract
►▼
Show Figures
Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is
[...] Read more.
Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is very high, which imposes a significant economic burden on both families and society. Steroid-associated osteonecrosis of the femoral head (SANFH) is the most common type of ONFH. However, the pathogenesis of SANFH remains unclear, and it is an urgent challenge for orthopedic surgeons to explore it. In this paper, the pathogenesis of SANFH and its related signaling pathways were briefly reviewed to enhance comprehension of the pathogenesis and prevention of SANFH.
Full article
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
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Topic in
Biomolecules, Cancers, Current Oncology, JCM, Onco
Extracellular Vesicles in Cancer Diagnosis and Treatment
Topic Editors: Shenglin Huang, Linlin Guo, Jialei WangDeadline: 20 July 2024
Topic in
Biomolecules, Cells, IJMS, Metabolites, Molecules
Bioactive Compounds and Therapeutics: Molecular Aspects, Metabolic Profiles, and Omics Studies
Topic Editors: Giovanni N. Roviello, Michele CostanzoDeadline: 20 September 2024
Topic in
Molecules, Pharmaceutics, Antibiotics, Microorganisms, Biomolecules, Marine Drugs, Polymers, IJMS
Antimicrobial Agents and Nanomaterials
Topic Editors: Sandra Pinto, Vasco D. B. BonifácioDeadline: 30 September 2024
Conferences
Special Issues
Special Issue in
Biomolecules
Role of Neuron-Glia and Glia-Glia Communications in the Brain Function: Recent Advances in the Central Nervous System Cellular Crosstalk and Signaling
Guest Editor: Nima SanadgolDeadline: 15 June 2024
Special Issue in
Biomolecules
Unveiling Protein Functions, Dynamics and Interactions in Health and Disease Using Experimental and Theoretical Approaches
Guest Editors: Daniele Di Marino, Cristina Maracci, Alice Romagnoli, Stefano MottaDeadline: 30 June 2024
Special Issue in
Biomolecules
New Advances of Cannabinoid Receptors in Health and Disease
Guest Editor: Balapal S. BasavarajappaDeadline: 15 July 2024
Special Issue in
Biomolecules
NMDA Receptor in Health and Diseases 2.0
Guest Editor: Motohiro OkadaDeadline: 31 July 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: Yuxiang Sun, Susanne Talcott