Biomolecules

21 pages, 8909 KiB

Open AccessArticle

The Role of MALAT1 in Regulating the Proangiogenic Functions, Invasion, and Migration of Trophoblasts in Selective Fetal Growth Restriction

by Shuting Xia, Yingnan Ye, Jialiu Liu, Hanfei Qiu, Minhuan Lin, Zhiming He, Linhuan Huang, Malie Wang and Yanmin Luo

Biomolecules 2024, 14(8), 988; https://doi.org/10.3390/biom14080988 (registering DOI) - 11 Aug 2024

Abstract

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, [...] Read more.

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects. Full article

(This article belongs to the Special Issue Placental-Related Disorders of Pregnancy II)

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11 pages, 5038 KiB

Open AccessArticle

The Potential of Immunotherapy for SMARCA4-Deficient Undifferentiated Uterine Sarcoma (SDUS)

by Xiaohong Yao, Ying He, Chaoxin Xiao, Ruihan Zhou, Chengjian Zhao and Wei Wang

Biomolecules 2024, 14(8), 987; https://doi.org/10.3390/biom14080987 (registering DOI) - 11 Aug 2024

Abstract

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune [...] Read more.

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune microenvironment of SDUS to evaluate the feasibility of utilizing immunotherapy. (2) Methods: Multiplex immunofluorescence (mIF) was employed to examine the immune microenvironment in two cases of SDUS in comparison to other subtypes of endometrial stromal sarcomas (ESSs). This research involved a comprehensive evaluation of immune cell infiltration, cellular interactions, and spatial organization within the tumor immune microenvironment (TiME). Statistical analysis was performed to assess differences in immune cell densities and interactions between SDUS and other ESSs. (3) Results: SDUS exhibited a significantly higher density of cytotoxic T lymphocytes (CTLs), T helper (Th) cells, B cells, and macrophages compared to other ESSs. Notable cellular interactions included Th–CTL and Th–B cell interactions, which were more prominent in SDUS. The spatial analysis revealed distinct immune niches characterized by lymphocyte aggregation and a vascular-rich environment, suggesting an active and engaged immune microenvironment in SDUS. (4) Conclusions: The results suggest that SDUS exhibits a highly immunogenic TiME, characterized by substantial lymphocyte infiltration and dynamic cellular interactions. These findings highlight the potential of immunotherapy as an effective treatment approach for SDUS. However, given the small number of samples evaluated, these conclusions should be drawn with caution. This study underscores the importance of additional investigation into immune-targeted therapies for this challenging cancer subtype, with a larger sample size to validate and expand upon these preliminary findings. Full article

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21 pages, 765 KiB

Open AccessReview

The Role of Epigenetic Mechanisms in the Pathogenesis of Hepatitis C Infection

by Justyna Żychowska, Maciej Ćmil, Patryk Skórka, Joanna Olejnik-Wojciechowska, Paulina Plewa, Estera Bakinowska, Kajetan Kiełbowski and Andrzej Pawlik

Biomolecules 2024, 14(8), 986; https://doi.org/10.3390/biom14080986 (registering DOI) - 10 Aug 2024

Abstract

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular [...] Read more.

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC. Full article

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15 pages, 2088 KiB

Open AccessArticle

Live Cell Monitoring of Phosphodiesterase Inhibition by Sulfonylurea Drugs

by Filip Berisha, Stefan Blankenberg and Viacheslav O. Nikolaev

Biomolecules 2024, 14(8), 985; https://doi.org/10.3390/biom14080985 (registering DOI) - 10 Aug 2024

Abstract

Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange protein directly activated by cAMP (Epac) was identified as [...] Read more.

Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange protein directly activated by cAMP (Epac) was identified as a new class of target proteins of SUs that might contribute to their antidiabetic effect, through the activation of the Ras-like guanosine triphosphatase Rap1, which has been controversially discussed. We used human embryonic kidney (HEK) 293 cells expressing genetic constructs of various Förster resonance energy transfer (FRET)-based biosensors containing different versions of Epac1 and Epac2 isoforms, alone or fused to different phosphodiesterases (PDEs), to monitor SU-induced conformational changes in Epac or direct PDE inhibition in real time. We show that SUs can both induce conformational changes in the Epac2 protein but not in Epac1, and directly inhibit the PDE3 and PDE4 families, thereby increasing cAMP levels in the direct vicinity of these PDEs. Furthermore, we demonstrate that the binding site of SUs in Epac2 is distinct from that of cAMP and is located between the amino acids E443 and E460. Using biochemical assays, we could also show that tolbutamide can inhibit PDE activity through an allosteric mechanism. Therefore, the cAMP-elevating capacity due to allosteric PDE inhibition in addition to direct Epac activation may contribute to the therapeutic effects of SU drugs. Full article

14 pages, 342 KiB

Open AccessReview

Use of Cosmetics in Pregnancy and Neurotoxicity: Can It Increase the Risk of Congenital Enteric Neuropathies?

by Kendra Jones, Lucas M. Wessel, Karl-Herbert Schäfer and María Ángeles Tapia-Laliena

Biomolecules 2024, 14(8), 984; https://doi.org/10.3390/biom14080984 (registering DOI) - 10 Aug 2024

Abstract

Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products [...] Read more.

Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy. Full article

(This article belongs to the Special Issue Pathogenesis and Potential Treatments of Neurointestinal Diseases)

14 pages, 2435 KiB

Open AccessReview

Computational Methods to Predict Conformational B-Cell Epitopes

by M. Carroll, E. Rosenbaum and R. Viswanathan

Biomolecules 2024, 14(8), 983; https://doi.org/10.3390/biom14080983 (registering DOI) - 10 Aug 2024

Abstract

Accurate computational prediction of B-cell epitopes can greatly enhance biomedical research and rapidly advance efforts to develop therapeutics, monoclonal antibodies, vaccines, and immunodiagnostic reagents. Previous research efforts have primarily focused on the development of computational methods to predict linear epitopes rather than conformational [...] Read more.

Accurate computational prediction of B-cell epitopes can greatly enhance biomedical research and rapidly advance efforts to develop therapeutics, monoclonal antibodies, vaccines, and immunodiagnostic reagents. Previous research efforts have primarily focused on the development of computational methods to predict linear epitopes rather than conformational epitopes; however, the latter is much more biologically predominant. Several conformational B-cell epitope prediction methods have recently been published, but their predictive performances are weak. Here, we present a review of the latest computational methods and assess their performances on a diverse test set of 29 non-redundant unbound antigen structures. Our results demonstrate that ISPIPab performs better than most methods and compares favorably with other recent antigen-specific methods. Finally, we suggest new strategies and opportunities to improve computational predictions of conformational B-cell epitopes. Full article

(This article belongs to the Special Issue Harnessing Protein Design and Engineering for Therapeutic Applications)

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15 pages, 4640 KiB

Open AccessArticle

Study of the Preparation and Properties of Chemically Modified Materials Based on Rapeseed Meal

by Sara Aquilia, Luca Rosi, Michele Pinna, Sabrina Bianchi, Walter Giurlani, Marco Bonechi, Francesco Ciardelli, Anna Maria Papini and Claudia Bello

Biomolecules 2024, 14(8), 982; https://doi.org/10.3390/biom14080982 (registering DOI) - 10 Aug 2024

Abstract

In recent years, there has been increasing interest in developing novel materials based on natural biopolymers as a renewable alternative to petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based [...] Read more.

In recent years, there has been increasing interest in developing novel materials based on natural biopolymers as a renewable alternative to petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study, we propose the use of rapeseed protein-rich meal as the main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewability. The application of sustainable products in the present high-tech society requires the modification of the basic native properties of these natural compounds. The original route proposed in this paper consists of preparation via the compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. An investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with guaranteed ecofriendly characteristics and mechanical properties adequate for specific structural applications. Full article

(This article belongs to the Collection Feature Papers in 'Biological and Bio- Materials' Section)

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13 pages, 988 KiB

Open AccessReview

Structural Perspectives on Metal Dependent Roles of Ferric Uptake Regulator (Fur)

by Sung-Min Kang, Hoon-Seok Kang, Woo-Hyun Chung, Kyu-Tae Kang and Do-Hee Kim

Biomolecules 2024, 14(8), 981; https://doi.org/10.3390/biom14080981 (registering DOI) - 9 Aug 2024

Abstract

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular [...] Read more.

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery. Full article

(This article belongs to the Topic Metalloproteins and Metalloenzymes)

17 pages, 719 KiB

Open AccessReview

Endothelial Cell Dysfunction Due to Molecules Secreted by Macrophages in Sepsis

by Heng He, Wei Zhang, Luofeng Jiang, Xirui Tong, Yongjun Zheng and Zhaofan Xia

Biomolecules 2024, 14(8), 980; https://doi.org/10.3390/biom14080980 (registering DOI) - 9 Aug 2024

Abstract

Sepsis is recognized as a syndrome of systemic inflammatory reaction induced by dysregulation of the body’s immunity against infection. The multiple organ dysfunction associated with sepsis is a serious threat to the patient’s life. Endothelial cell dysfunction has been extensively studied in sepsis. [...] Read more.

Sepsis is recognized as a syndrome of systemic inflammatory reaction induced by dysregulation of the body’s immunity against infection. The multiple organ dysfunction associated with sepsis is a serious threat to the patient’s life. Endothelial cell dysfunction has been extensively studied in sepsis. However, the role of macrophages in sepsis is not well understood and the intrinsic link between the two cells has not been elucidated. Macrophages are first-line cells of the immune response, whereas endothelial cells are a class of cells that are highly altered in function and morphology. In sepsis, various cytokines secreted by macrophages and endothelial cell dysfunction are inextricably linked. Therefore, investigating how macrophages affect endothelial cells could offer a theoretical foundation for the treatment of sepsis. This review links molecules (TNF-α, CCL2, ROS, VEGF, MMP-9, and NO) secreted by macrophages under inflammatory conditions to endothelial cell dysfunction (adhesion, permeability, and coagulability), refining the pathophysiologic mechanisms of sepsis. At the same time, multiple approaches (a variety of miRNA and medicines) regulating macrophage polarization are also summarized, providing new insights into reversing endothelial cell dysfunction and improving the outcome of sepsis treatment. Full article

(This article belongs to the Special Issue The Role of Modulating Intracellular Signaling in Immune System)

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11 pages, 2026 KiB

Open AccessArticle

Major Adverse Cardiovascular Events: The Importance of Serum Levels and Haplotypes of the Anti-Inflammatory Cytokine Interleukin 10

by Susanne Schulz, Leonie Reuter, Alexander Navarrete Santos, Kerstin Bitter, Selina Rehm, Axel Schlitt and Stefan Reichert

Biomolecules 2024, 14(8), 979; https://doi.org/10.3390/biom14080979 - 9 Aug 2024

Abstract

Background: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine [...] Read more.

Background: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. Patients and methods: At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). Results: In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). Conclusion: In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients. Full article

(This article belongs to the Special Issue Biomarkers of Cardiovascular and Cerebrovascular Diseases)

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28 pages, 6893 KiB

Open AccessReview

Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets

by Sai Zhang, Daocheng Li, Mingyuan Fan, Jiushu Yuan, Chunguang Xie, Haipo Yuan, Hongyan Xie and Hong Gao

Biomolecules 2024, 14(8), 978; https://doi.org/10.3390/biom14080978 - 9 Aug 2024

Abstract

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA [...] Read more.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA. Full article

(This article belongs to the Special Issue New Insights into Reactive Oxygen Species in Cell Death and Immunity)

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18 pages, 5372 KiB

Open AccessArticle

Elucidating the Subcellular Localization of GLRaV-3 Proteins Encoded by the Unique Gene Block in N. benthamiana Suggests Implications on Plant Host Suppression

by Patrick Lameront, Mehdi Shabanian, Laura M. J. Currie, Catherine Fust, Caihong Li, Alyssa Clews and Baozhong Meng

Biomolecules 2024, 14(8), 977; https://doi.org/10.3390/biom14080977 - 9 Aug 2024

Abstract

Grapevine leafroll-associated virus 3 (GLRaV-3) is a formidable threat to the stability of the global grape and wine industries. It is the primary etiological agent of grapevine leafroll disease (GLD) and significantly impairs vine health, fruit quality, and yield. GLRaV-3 is a member [...] Read more.

Grapevine leafroll-associated virus 3 (GLRaV-3) is a formidable threat to the stability of the global grape and wine industries. It is the primary etiological agent of grapevine leafroll disease (GLD) and significantly impairs vine health, fruit quality, and yield. GLRaV-3 is a member of the genus Ampelovirus, Closteroviridae family. Viral genes within the 3′ proximal unique gene blocks (UGB) remain highly variable and poorly understood. The UGBs of Closteroviridae viruses include diverse open reading frames (ORFs) that have been shown to contribute to viral functions such as the suppression of the host RNA silencing defense response and systemic viral spread. This study investigates the role of GLRaV-3 ORF8, ORF9, and ORF10, which encode the proteins p21, p20A, and p20B, respectively. These genes represent largely unexplored facets of the GLRaV-3 genome. Here, we visualize the subcellular localization of wildtype and mutagenized GLRaV-3 ORFs 8, 9, and 10, transiently expressed in Nicotiana benthamiana. Our results indicate that p21 localizes to the cytosol, p20A associates with microtubules, and p20B is trafficked into the nucleus to carry out the suppression of host RNA silencing. The findings presented herein provide a foundation for future research aimed at the characterization of the functions of these ORFs. In the long run, it would also facilitate the development of innovative strategies to understand GLRaV-3, mitigate its spread, and impacts on grapevines and the global wine industry. Full article

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20 pages, 3385 KiB

Open AccessArticle

DNA Methylation of PXDN Is Associated with Early-Life Adversity in Adult Mental Disorders

by Susanne Edelmann, Jeysri Balaji, Sarah Pasche, Ariane Wiegand and Vanessa Nieratschker

Biomolecules 2024, 14(8), 976; https://doi.org/10.3390/biom14080976 - 9 Aug 2024

Abstract

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA [...] Read more.

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA and the risk of an adult mental disorder is still not fully understood. Evidence is emerging that long-lasting changes in the epigenetic processes regulating gene expression, such as DNA methylation, play an important role in the biological mechanisms linking ELA and mental disorders. Based on a recent study, we analyzed the DNA methylation of a specific CpG site within the gene PXDN—cg10888111—in blood in the context of ELA across a set of psychiatric disorders, namely Borderline Personality Disorder (BPD), Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD), and its potential contribution to their pathogenesis. We found significant hypermethylation in mentally ill patients with high levels of ELA compared to patients with low levels of ELA, whereas cg10888111 methylation in healthy control individuals was not affected by ELA. Further investigations revealed that this effect was driven by the MDD cohort. Providing a direct comparison of cg10888111 DNA methylation in blood in the context of ELA across three mental disorders, our results indicate the role of PXDN regulation in the response to ELA in the pathogenesis of mental disorders, especially MDD. Further studies will be needed to validate these results and decipher the corresponding biological network that is involved in the transmission of ELA to an adult mental disorder in general. Full article

(This article belongs to the Special Issue Molecular Basis of Stress- and Trauma-Related Disorders)

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26 pages, 6243 KiB

Open AccessReview

Putting It All Together: The Roles of Ribosomal Proteins in Nucleolar Stages of 60S Ribosomal Assembly in the Yeast Saccharomyces cerevisiae

by Taylor N. Ayers and John L. Woolford

Biomolecules 2024, 14(8), 975; https://doi.org/10.3390/biom14080975 - 9 Aug 2024

Abstract

Here we review the functions of ribosomal proteins (RPs) in the nucleolar stages of large ribosomal subunit assembly in the yeast Saccharomyces cerevisiae. We summarize the effects of depleting RPs on pre-rRNA processing and turnover, on the assembly of other RPs, and [...] Read more.

Here we review the functions of ribosomal proteins (RPs) in the nucleolar stages of large ribosomal subunit assembly in the yeast Saccharomyces cerevisiae. We summarize the effects of depleting RPs on pre-rRNA processing and turnover, on the assembly of other RPs, and on the entry and exit of assembly factors (AFs). These results are interpreted in light of recent near-atomic-resolution cryo-EM structures of multiple assembly intermediates. Results are discussed with respect to each neighborhood of RPs and rRNA. We identify several key mechanisms related to RP behavior. Neighborhoods of RPs can assemble in one or more than one step. Entry of RPs can be triggered by molecular switches, in which an AF is replaced by an RP binding to the same site. To drive assembly forward, rRNA structure can be stabilized by RPs, including clamping rRNA structures or forming bridges between rRNA domains. Full article

(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)

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16 pages, 5630 KiB

Open AccessArticle

Angiotensin II Alters Mitochondrial Membrane Potential and Lipid Metabolism in Rat Colonic Epithelial Cells

by Darby D. Toth, Christopher L. Souder II, Sarah Patuel, Cole D. English, Isaac Konig, Emma Ivantsova, Wendi Malphurs, Jacqueline Watkins, Kaylie Anne Costa, John A. Bowden, Jasenka Zubcevic and Christopher J. Martyniuk

Biomolecules 2024, 14(8), 974; https://doi.org/10.3390/biom14080974 - 9 Aug 2024

Abstract

An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells [...] Read more.

An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1–5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 (PDK2) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism. Full article

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3 pages, 158 KiB

Open AccessEditorial

Redox Imbalance and Mitochondrial Abnormalities in Kidney Disease—Volume II

by Tram N. Diep, Haoxin Liu, Ying Wang, Yucheng Wang, David Hoogewijs and Liang-Jun Yan

Biomolecules 2024, 14(8), 973; https://doi.org/10.3390/biom14080973 - 9 Aug 2024

Abstract

The kidney performs fundamental functions by eliminating metabolic waste and reabsorbing essential nutrients and electrolytes such as glucose, proteins, ions, and anions [...] Full article

(This article belongs to the Special Issue Redox Imbalance and Mitochondrial Abnormalities in Kidney Disease II)

34 pages, 669 KiB

Open AccessReview

Omics Science and Social Aspects in Detecting Biomarkers for Diagnosis, Risk Prediction, and Outcomes of Carotid Stenosis

by Davide Costa, Enrica Scalise, Nicola Ielapi, Umberto Marcello Bracale, Teresa Faga, Ashour Michael, Michele Andreucci and Raffaele Serra

Biomolecules 2024, 14(8), 972; https://doi.org/10.3390/biom14080972 - 8 Aug 2024

Abstract

Carotid stenosis is characterized by the progressive narrowing of the carotid arteries due to the formation of atherosclerotic plaque, which can lead to stroke and death as major complications. Numerous biomarkers allow for its study and characterization, particularly those related to “omics” sciences. [...] Read more.

Carotid stenosis is characterized by the progressive narrowing of the carotid arteries due to the formation of atherosclerotic plaque, which can lead to stroke and death as major complications. Numerous biomarkers allow for its study and characterization, particularly those related to “omics” sciences. Through the most common research databases, we report representative studies about carotid stenosis biomarkers based on genomics, transcriptomics, proteomics, and metabolomics in a narrative review. To establish a priority among studies based on their internal validity, we used a quality assessment tool, the Scale for the Assessment of Narrative Review Articles (SANRA). Genes, transcriptomes, proteins, and metabolites can diagnose the disease, define plaque connotations, predict consequences after revascularization interventions, and associate carotid stenosis with other patient comorbidities. It also emerged that many aspects determining the patient’s psychological and social sphere are implicated in carotid disease. In conclusion, when taking the multidisciplinary approach that combines human sciences with biological sciences, it is possible to comprehensively define a patient’s health and thus improve their clinical management through precision medicine. Full article

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17 pages, 1501 KiB

Open AccessReview

Biological Properties of Sandalwood Oil and Microbial Synthesis of Its Major Sesquiterpenoids

by Xiaoguang Yan, Sichone Daniel David, Guangzhao Du, Weiguo Li, Dongmei Liang, Shengxin Nie, Mingyue Ge, Chen Wang, Jianjun Qiao, Yanni Li and Qinggele Caiyin

Biomolecules 2024, 14(8), 971; https://doi.org/10.3390/biom14080971 - 8 Aug 2024

Abstract

Sandalwood essential oil is extracted from the heartwood part of mature sandalwood and is known for its pleasant fragrance and exceptional medicinal activities, including antimicrobial, antitumor, and anti-inflammatory properties. The (Z)-α-santalol and (Z)-β-santalol are the most vital ingredients contributing to sandalwood oil’s bioactivities [...] Read more.

Sandalwood essential oil is extracted from the heartwood part of mature sandalwood and is known for its pleasant fragrance and exceptional medicinal activities, including antimicrobial, antitumor, and anti-inflammatory properties. The (Z)-α-santalol and (Z)-β-santalol are the most vital ingredients contributing to sandalwood oil’s bioactivities and unique woody odor characteristics. Metabolic engineering strategies have shown promise in transforming microorganisms such as yeast and bacteria into effective cell factories for enhancing the production of vital sesquiterpenes (santalene and santalol) found in sandalwood oil. This review aims to summarize sources of sandalwood oil, its components/ingredients, and its applications. It also highlights the biosynthesis of santalene and santalol and the various metabolic engineering strategies employed to reconstruct and enhance santalene and santalol biosynthesis pathways in heterologous hosts. Full article

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23 pages, 1736 KiB

Open AccessReview

Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis

by Yi Chen, Hefang Xiao, Zirui Liu, Fei Teng, Ao Yang, Bin Geng, Xiaoyun Sheng and Yayi Xia

Biomolecules 2024, 14(8), 970; https://doi.org/10.3390/biom14080970 - 8 Aug 2024

Abstract

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a [...] Read more.

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that regulates a variety of cellular metabolisms, including inflammation, tumorigenesis, and bone metabolism. Recent studies have emphasized the important role of SIRT1 in bone homeostasis. This article reviews the role of SIRT1 in bone metabolism and OP and also discusses therapeutic strategies and future research directions for targeting SIRT1. Full article

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Biomolecules

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