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
Recent Research Progress on Polyamidoamine-Engineered Hydrogels for Biomedical Applications
Biomolecules 2024, 14(6), 620; https://doi.org/10.3390/biom14060620 (registering DOI) - 24 May 2024
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Hydrogels are three-dimensional crosslinked functional materials with water-absorbing and swelling properties. Many hydrogels can store a variety of small functional molecules to structurally and functionally mimic the natural extracellular matrix; hence, they have been extensively studied for biomedical applications. Polyamidoamine (PAMAM) dendrimers have
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Hydrogels are three-dimensional crosslinked functional materials with water-absorbing and swelling properties. Many hydrogels can store a variety of small functional molecules to structurally and functionally mimic the natural extracellular matrix; hence, they have been extensively studied for biomedical applications. Polyamidoamine (PAMAM) dendrimers have an ethylenediamine core and a large number of peripheral amino groups, which can be used to engineer various polymer hydrogels. In this review, an update on the progress of using PAMAM dendrimers for multifunctional hydrogel design was given. The synthesis of these hydrogels, which includes click chemistry reactions, aza-Michael addition, Schiff base reactions, amidation reactions, enzymatic reactions, and radical polymerization, together with research progress in terms of their application in the fields of drug delivery, tissue engineering, drug-free tumor therapy, and other related fields, was discussed in detail. Furthermore, the biomedical applications of PAMAM-engineered nano-hydrogels, which combine the advantages of dendrimers, hydrogels, and nanoparticles, were also summarized. This review will help researchers to design and develop more functional hydrogel materials based on PAMAM dendrimers.
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Open AccessArticle
Comprehensive Bio-Screening of Phytochemistry and Biological Capacity of Oregano (Origanum vulgare) and Salvia triloba Extracts against Oral Cariogenic and Food-Origin Pathogenic Bacteria
by
Maria Antoniadou, Georgios Rozos, Natalia Vaou, Konstantinos Zaralis, Caglar Ersanli, Athanasios Alexopoulos, Aikaterini Dadamogia, Theodoros Varzakas, Athina Tzora and Chrysoula (Chrysa) Voidarou
Biomolecules 2024, 14(6), 619; https://doi.org/10.3390/biom14060619 - 24 May 2024
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This study utilized phytochemical screening to conduct the qualitative analysis of plant extracts, aiming to identify various classes of secondary metabolites. Moreover, the antibacterial activity of different types of Oregano vulgare and Salvia triloba extracts was determined. To achieve the aim of this
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This study utilized phytochemical screening to conduct the qualitative analysis of plant extracts, aiming to identify various classes of secondary metabolites. Moreover, the antibacterial activity of different types of Oregano vulgare and Salvia triloba extracts was determined. To achieve the aim of this study, aqueous, ethanolic, and enzymatic extracts were prepared and screened for phytochemical capacity and antioxidant activities. The determination of the antibacterial activity included phenotypic screening of antibiotic susceptibility pattern of oral and food pathogenic bacterial strains, determination of the minimum inhibitory concentration and minimum bactericidal concentration—via microdilution broth test and in vitro valuation of antibacterial efficacies—of the anti-biofilm properties of the studied herbal extractions. Results: Our study evaluated the phytochemical composition and the antioxidant, antibacterial, and anti-biofilm properties of O. vulgare and S. triloba extracts. The analyzed samples contained bioactive compounds, such as phenolics and flavonoids, contributing to the observed strong antioxidant effect. Furthermore, they exhibited notable activity against oral biofilm formation and demonstrated significant antibacterial efficacy against dental caries’ microorganisms as well as food pathogens. Despite methodological variations, all extracts showed significant antioxidant capacity and promising antibacterial activity against various pathogens, including resistant strains, while also inhibiting biofilm formation. Although limited to two plant species and facing methodological constraints, this study lays the groundwork for future research, indicating the therapeutic potential of O. vulgare and S. triloba extracts. Further exploration is needed to report on underlying mechanisms and validate efficacy through clinical trials.
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Open AccessArticle
Polyphenol Compound 18a Modulates UCP1-Dependent Thermogenesis to Counteract Obesity
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Xueping Wen, Yufei Song, Mei Zhang, Yiping Kang, Dandan Chen, Hui Ma, Fajun Nan, Yanan Duan and Jingya Li
Biomolecules 2024, 14(6), 618; https://doi.org/10.3390/biom14060618 - 23 May 2024
Abstract
Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat,
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Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered 18a, a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that 18a prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of 18a-induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by 18a via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound 18a and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.
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(This article belongs to the Topic Natural Products and Drug Discovery)
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Open AccessArticle
Sequence-Based Viscosity Prediction for Rapid Antibody Engineering
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Bram Estes, Mani Jain, Lei Jia, John Whoriskey, Brian Bennett and Hailing Hsu
Biomolecules 2024, 14(6), 617; https://doi.org/10.3390/biom14060617 - 23 May 2024
Abstract
Through machine learning, identifying correlations between amino acid sequences of antibodies and their observed characteristics, we developed an internal viscosity prediction model to empower the rapid engineering of therapeutic antibody candidates. For a highly viscous anti-IL-13 monoclonal antibody, we used a structure-based rational
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Through machine learning, identifying correlations between amino acid sequences of antibodies and their observed characteristics, we developed an internal viscosity prediction model to empower the rapid engineering of therapeutic antibody candidates. For a highly viscous anti-IL-13 monoclonal antibody, we used a structure-based rational design strategy to generate a list of variants that were hypothesized to mitigate viscosity. Our viscosity prediction tool was then used as a screen to cull virtually engineered variants with a probability of high viscosity while advancing those with a probability of low viscosity to production and testing. By combining the rational design engineering strategy with the in silico viscosity prediction screening step, we were able to efficiently improve the highly viscous anti-IL-13 candidate, successfully decreasing the viscosity at 150 mg/mL from 34 cP to 13 cP in a panel of 16 variants.
Full article
(This article belongs to the Special Issue Harnessing Protein Design and Engineering for Therapeutic Applications)
Open AccessReview
Adenomyosis and Abnormal Uterine Bleeding: Review of the Evidence
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Marwan Habiba, Sun-Wei Guo and Giuseppe Benagiano
Biomolecules 2024, 14(6), 616; https://doi.org/10.3390/biom14060616 - 23 May 2024
Abstract
Background: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the “expected” presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high
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Background: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the “expected” presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high incidence of adenomyosis in uteri removed for indications other than AUB or dysmenorrhea. Here, we examine evidence for the link between adenomyosis and AUB. Methods: A comprehensive Medline literature review of all publications to October 2023. Results: Sixty-three articles were identified and included in the review. Despite a large body of studies, the available literature does not provide conclusive evidence of a link between adenomyosis and AUB. This is because of unsuitable study design, or poor characterization of the study population or of the inclusion or exclusion criteria. Additional challenges arise because of the lack of agreed criteria for diagnosing adenomyosis and the often absence of detailed assessment of menstrual blood loss. Adenomyosis often coexists with other conditions that have also been linked to similar symptoms, and many cases of adenomyosis are asymptomatic. Conclusion: Most of the existing literature and studies that addressed treatment outcome of adenomyosis started from the premise that a link between the condition and AUB had been proven. Yet, published information shows that aspects such a relationship is still uncertain. Further research is needed to address the relation between AUB and adenomyosis burden (or subtypes), distribution, and concomitant pathology.
Full article
(This article belongs to the Special Issue Human Reproductive Biology: Uncertainties and Controversies)
Open AccessArticle
Crystal Violet Selectively Detects Aβ Oligomers but Not Fibrils In Vitro and in Alzheimer’s Disease Brain Tissue
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Kanchana Karunarathne, Teresa R. Kee, Hanna Jeon, Sara Cazzaro, Yasith I. Gamage, Jianjun Pan, Jung-A. A. Woo, David E. Kang and Martin Muschol
Biomolecules 2024, 14(6), 615; https://doi.org/10.3390/biom14060615 - 23 May 2024
Abstract
Deposition of extracellular Amyloid Beta (Aβ) and intracellular tau fibrils in post-mortem brains remains the only way to conclusively confirm cases of Alzheimer’s Disease (AD). Substantial evidence, though, implicates small globular oligomers instead of fibrils as relevant biomarkers of, and critical contributors to,
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Deposition of extracellular Amyloid Beta (Aβ) and intracellular tau fibrils in post-mortem brains remains the only way to conclusively confirm cases of Alzheimer’s Disease (AD). Substantial evidence, though, implicates small globular oligomers instead of fibrils as relevant biomarkers of, and critical contributors to, the clinical symptoms of AD. Efforts to verify and utilize amyloid oligomers as AD biomarkers in vivo have been limited by the near-exclusive dependence on conformation-selective antibodies for oligomer detection. While antibodies have yielded critical evidence for the role of both Aβ and tau oligomers in AD, they are not suitable for imaging amyloid oligomers in vivo. Therefore, it would be desirable to identify a set of oligomer-selective small molecules for subsequent development into Positron Emission Tomography (PET) probes. Using a kinetics-based screening assay, we confirm that the triarylmethane dye Crystal Violet (CV) is oligomer-selective for Aβ42 oligomers (AβOs) grown under near-physiological solution conditions in vitro. In postmortem brains of an AD mouse model and human AD patients, we demonstrate that A11 antibody-positive oligomers but not Thioflavin S (ThioS)-positive fibrils colocalize with CV staining, confirming in vitro results. Therefore, our kinetic screen represents a robust approach for identifying new classes of small molecules as candidates for oligomer-selective dyes (OSDs). Such OSDs, in turn, provide promising starting points for the development of PET probes for pre-mortem imaging of oligomer deposits in humans.
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(This article belongs to the Section Molecular Biomarkers)
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Open AccessReview
New Frontiers in Potato Breeding: Tinkering with Reproductive Genes and Apomixis
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Diego Hojsgaard, Manuela Nagel, Sergio E. Feingold, Gabriela A. Massa and John E. Bradshaw
Biomolecules 2024, 14(6), 614; https://doi.org/10.3390/biom14060614 - 23 May 2024
Abstract
Potato is the most important non-cereal crop worldwide, and, yet, genetic gains in potato have been traditionally delayed by the crop’s biology, mostly the genetic heterozygosity of autotetraploid cultivars and the intricacies of the reproductive system. Novel site-directed genetic modification techniques provide opportunities
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Potato is the most important non-cereal crop worldwide, and, yet, genetic gains in potato have been traditionally delayed by the crop’s biology, mostly the genetic heterozygosity of autotetraploid cultivars and the intricacies of the reproductive system. Novel site-directed genetic modification techniques provide opportunities for designing climate-smart cultivars, but they also pose new possibilities (and challenges) for breeding potato. As potato species show a remarkable reproductive diversity, and their ovules have a propensity to develop apomixis-like phenotypes, tinkering with reproductive genes in potato is opening new frontiers in potato breeding. Developing diploid varieties instead of tetraploid ones has been proposed as an alternative way to fill the gap in genetic gain, that is being achieved by using gene-edited self-compatible genotypes and inbred lines to exploit hybrid seed technology. In a similar way, modulating the formation of unreduced gametes and synthesizing apomixis in diploid or tetraploid potatoes may help to reinforce the transition to a diploid hybrid crop or enhance introgression schemes and fix highly heterozygous genotypes in tetraploid varieties. In any case, the induction of apomixis-like phenotypes will shorten the time and costs of developing new varieties by allowing the multi-generational propagation through true seeds. In this review, we summarize the current knowledge on potato reproductive phenotypes and underlying genes, discuss the advantages and disadvantages of using potato’s natural variability to modulate reproductive steps during seed formation, and consider strategies to synthesize apomixis. However, before we can fully modulate the reproductive phenotypes, we need to understand the genetic basis of such diversity. Finally, we visualize an active, central role for genebanks in this endeavor by phenotyping properly genotyped genebank accessions and new introductions to provide scientists and breeders with reliable data and resources for developing innovations to exploit market opportunities.
Full article
(This article belongs to the Special Issue Molecular Plant Reproduction: From Cells to Nature)
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Open AccessArticle
CircInpp5b Ameliorates Renal Interstitial Fibrosis by Promoting the Lysosomal Degradation of DDX1
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Xi Fang, Chengyuan Tang, Dong Zeng, Yi Shan, Qianfang Liu, Xuemin Yin and Ying Li
Biomolecules 2024, 14(6), 613; https://doi.org/10.3390/biom14060613 - 23 May 2024
Abstract
Renal interstitial fibrosis (RIF) is a classic pathophysiological process of chronic kidney disease (CKD). However, the mechanisms underlying RIF remain unclear. The present study found that a novel circular RNA, cirInpp5b, might be involved in RIF by high-throughput sequencing. Subsequent experiments revealed that
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Renal interstitial fibrosis (RIF) is a classic pathophysiological process of chronic kidney disease (CKD). However, the mechanisms underlying RIF remain unclear. The present study found that a novel circular RNA, cirInpp5b, might be involved in RIF by high-throughput sequencing. Subsequent experiments revealed that circInpp5b was reduced in UUO mouse kidney tissues and TGF-β1-treated proximal tubular cells. The overexpression of circInpp5b inhibited RIF in UUO mice and prevented extracellular matrix (ECM) deposition in TGF-β1-treated proximal tubular cells. Furthermore, overexpression of circInpp5b down-regulated the protein level of DDX1. Mechanistically, circInpp5b bound to the DDX1 protein and promoted its lysosomal degradation. Collectively, the findings of our study demonstrate that circInpp5b ameliorates RIF by binding to the DDX1 protein and promoting its lysosomal degradation.
Full article
(This article belongs to the Special Issue New Insights into Kidney Disease Development and Therapy Strategies)
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Open AccessArticle
Microfluidic System-Based Quantitative Analysis of Platelet Function through Speckle Size Measurement
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Jong Hyeok Han, Inkwon Yoon and Hee-Jae Jeon
Biomolecules 2024, 14(6), 612; https://doi.org/10.3390/biom14060612 - 23 May 2024
Abstract
Platelets play essential roles in the formation of blood clots by clumping with coagulation factors at the site of vascular injury to stop bleeding; therefore, a reduction in the platelet number or disorder in their function causes bleeding risk. In our research, we
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Platelets play essential roles in the formation of blood clots by clumping with coagulation factors at the site of vascular injury to stop bleeding; therefore, a reduction in the platelet number or disorder in their function causes bleeding risk. In our research, we developed a method to assess platelet aggregation using an optical approach within a microfluidic chip’s channel by evaluating the size of laser speckles. These speckles, associated with slowed blood flow in the microfluidic channel, had a baseline size of 28.54 ± 0.72 µm in whole blood. Removing platelets from the sample led to a notable decrease in speckle size to 27.04 ± 1.23 µm. Moreover, the addition of an ADP-containing agonist, which activates platelets, resulted in an increased speckle size of 32.89 ± 1.69 µm. This finding may provide a simple optical method via microfluidics that could be utilized to assess platelet functionality in diagnosing bleeding disorders and potentially in monitoring therapies that target platelets.
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(This article belongs to the Special Issue New Discoveries in Biological Functions of Platelet)
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Open AccessArticle
Advances in the Toxicity Assessment of Silver Nanoparticles Derived from a Sphagnum fallax Extract for Monolayers and Spheroids
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Liliya Iskuzhina, Svetlana Batasheva, Marina Kryuchkova, Artem Rozhin, Mariya Zolotykh, Rimma Mingaleeva, Farida Akhatova, Anna Stavitskaya, Kirill Cherednichenko and Elvira Rozhina
Biomolecules 2024, 14(6), 611; https://doi.org/10.3390/biom14060611 - 22 May 2024
Abstract
The production of nanomaterials through environmentally friendly methods is a top priority in the sustainable development of nanotechnology. This paper presents data on the synthesis of silver nanoparticles using an aqueous extract of Sphagnum fallax moss at room temperature. The morphology, stability, and
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The production of nanomaterials through environmentally friendly methods is a top priority in the sustainable development of nanotechnology. This paper presents data on the synthesis of silver nanoparticles using an aqueous extract of Sphagnum fallax moss at room temperature. The morphology, stability, and size of the nanoparticles were analyzed using various techniques, including transmission electron microscopy, Doppler laser velocimetry, and UV-vis spectroscopy. In addition, Fourier transform infrared spectroscopy was used to analyze the presence of moss metabolites on the surface of nanomaterials. The effects of different concentrations of citrate-stabilized and moss extract-stabilized silver nanoparticles on cell viability, necrosis induction, and cell impedance were compared. The internalization of silver nanoparticles into both monolayers and three-dimensional cells spheroids was evaluated using dark-field microscopy and hyperspectral imaging. An eco-friendly method for the synthesis of silver nanoparticles at room temperature is proposed, which makes it possible to obtain spherical nanoparticles of 20–30 nm in size with high bioavailability and that have potential applications in various areas of human life.
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(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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Open AccessArticle
Globospiramine Exhibits Inhibitory and Fungicidal Effects against Candida albicans via Apoptotic Mechanisms
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Joe Anthony H. Manzano, Simone Brogi, Vincenzo Calderone, Allan Patrick G. Macabeo and Nicanor Austriaco
Biomolecules 2024, 14(6), 610; https://doi.org/10.3390/biom14060610 - 22 May 2024
Abstract
Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of an available structurally diverse antifungal drug armamentarium. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of
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Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of an available structurally diverse antifungal drug armamentarium. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro anticandidal activities of globospiramine against two clinically relevant Candida species (C. albicans and C. tropicalis) and the exploration of its possible target proteins using in silico methods. Thus, the colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid along with a decrease in the number of viable CFUs by almost 50% at 60 min after treatment. The results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 8 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed well with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments suggested globospiramine to bind strongly with 1,3-β-glucan synthase and Als3 adhesin—enzymes indirectly involved in apoptosis-driven candidal inhibition.
Full article
(This article belongs to the Special Issue Research into Bioactive Natural Compounds: New Molecules, Bioinspired Syntheses, Biotechnological Methods and Bioassays—Celebrating the Pioneering Work of Prof. Alejandro Fernandez Barrero)
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Open AccessArticle
Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)
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Sheethal Thomas Mannully, Rawan Mahajna, Huda Nazzal, Salam Maree, Hongchao Zheng, Daniel H. Appella, Reuven Reich and Eylon Yavin
Biomolecules 2024, 14(6), 609; https://doi.org/10.3390/biom14060609 - 22 May 2024
Abstract
Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on
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Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.
Full article
(This article belongs to the Section Biomacromolecules: Nucleic Acids)
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Open AccessReview
Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications
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Xiangyu Meng, Xiao Bai, Angting Ke, Kaiqiang Li, Yun Lei, Siqi Ding and Dongqiu Dai
Biomolecules 2024, 14(6), 608; https://doi.org/10.3390/biom14060608 - 22 May 2024
Abstract
Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent
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Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent relapse and metastasis. The current treatment strategies have limited overall efficacy because of intrinsic or acquired drug resistance. Recent evidence suggests that dysregulated long non-coding RNAs (lncRNAs) play a significant role in mediating drug resistance in GC. Therefore, there is an imperative to explore novel molecular mechanisms underlying drug resistance in order to overcome this challenging issue. With advancements in deep transcriptome sequencing technology, lncRNAs—once considered transcriptional noise—have garnered widespread attention as potential regulators of carcinogenesis, including tumor cell proliferation, metastasis, and sensitivity to chemo- or radiotherapy through multiple regulatory mechanisms. In light of these findings, we aim to review the mechanisms by which lncRNAs contribute to drug therapy resistance in GC with the goal of providing new insights and breakthroughs toward overcoming this formidable obstacle.
Full article
(This article belongs to the Section Biomacromolecules: Nucleic Acids)
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Open AccessArticle
Single-Nucleus RNA-Seq Reveals Spermatogonial Stem Cell Developmental Pattern in Shaziling Pigs
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Xiangwei Tang, Chujie Chen, Saina Yan, Anqi Yang, Yanhong Deng, Bin Chen and Jingjing Gu
Biomolecules 2024, 14(6), 607; https://doi.org/10.3390/biom14060607 - 21 May 2024
Abstract
Normal testicular development ensures the process of spermatogenesis, which is a complex biological process. The sustained high productivity of spermatogenesis throughout life is predominantly attributable to the constant proliferation and differentiation of spermatogonial stem cells (SSCs). The self-renewal and differentiation processes of SSCs
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Normal testicular development ensures the process of spermatogenesis, which is a complex biological process. The sustained high productivity of spermatogenesis throughout life is predominantly attributable to the constant proliferation and differentiation of spermatogonial stem cells (SSCs). The self-renewal and differentiation processes of SSCs are strictly regulated by the SSC niche. Therefore, understanding the developmental pattern of SSCs is crucial for spermatogenesis. The Shaziling pig is a medium-sized indigenous pig breed originating from central China. It is renowned for its superior meat quality and early male sexual maturity. The spermatogenic ability of the boars is of great economic importance to the pig industry. To investigate testicular development, particularly the pattern of SSC development in Shaziling pigs, we used single-cell transcriptomics to identify gene expression patterns in 82,027 individual cells from nine Shaziling pig testes at three key postnatal developmental stages. We generated an unbiased cell developmental atlas of Shaziling pig testicular tissues. We elucidated the complex processes involved in the development of SSCs within their niche in the Shaziling pig. Specifically, we identified potential marker genes and cellular signaling pathways that regulate SSC self-renewal and maintenance. Additionally, we proposed potential novel marker genes for SSCs that could be used for SSC isolation and sorting in Shaziling pigs. Furthermore, by immunofluorescence staining of testicular tissues of different developmental ages using marker proteins (UCHL1 and KIT), the developmental pattern of the spermatogonia of Shaziling pigs was intensively studied. Our research enhances the comprehension of the development of SSCs and provides a valuable reference for breeding Shaziling pigs.
Full article
(This article belongs to the Section Molecular Reproduction)
Open AccessArticle
Activation of Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) in Keratinocytes by Endogenous Fatty Acids
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Bokai Zhu, Xiaoyang Zhu, Michael G. Borland, Douglas H. Ralph, Christopher R. Chiaro, Kristopher W. Krausz, James M. Ntambi, Adam B. Glick, Andrew D. Patterson, Gary H. Perdew, Frank J. Gonzalez and Jeffrey M. Peters
Biomolecules 2024, 14(6), 606; https://doi.org/10.3390/biom14060606 - 21 May 2024
Abstract
Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS
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Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 (Angptl4) mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 (Scd1) mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing Pparb/d-null keratinocytes. HRAS-expressing Scd1-null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components.
Full article
(This article belongs to the Special Issue Peroxisome Proliferator-Activated Receptors (PPARs): A Themed Issue in Honor of Prof. Walter Wahli)
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Open AccessArticle
Efficacy of the Probiotic L. brevis in Counteracting the Demineralizing Process of the Tooth Enamel Surface: Results from an In Vitro Study
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Serena Altamura, Francesca Rosaria Augello, Eleonora Ortu, Davide Pietropaoli, Benedetta Cinque, Mario Giannoni and Francesca Lombardi
Biomolecules 2024, 14(5), 605; https://doi.org/10.3390/biom14050605 - 20 May 2024
Abstract
Background. Enamel plays an essential role in protecting the underlying layers of the human tooth; therefore, preserving it is vital. This experimental study aimed to evaluate the potential ability of L. brevis to counteract the action of a demineralizing agent on dental enamel
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Background. Enamel plays an essential role in protecting the underlying layers of the human tooth; therefore, preserving it is vital. This experimental study aimed to evaluate the potential ability of L. brevis to counteract the action of a demineralizing agent on dental enamel morphology and mineral composition in vitro. Methods. The sample consisted of 12 healthy human posterior teeth. The coronal portion of each tooth was subdivided into two equal parts longitudinally. The specimens were randomly divided into four groups: artificial saliva, L. brevis suspension, demineralizing agent (DA), and DA plus L. brevis. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate the surface micromorphology and the mineral content, respectively. The statistical analysis was conducted using a one-way ANOVA, followed by Tukey’s post hoc test. Results. SEM analysis did not highlight significant changes in the enamel microstructure of L. brevis-treated specimens compared to the control. DA-induced damage to the enamel structure was drastically reduced when the specimens were contextually exposed to the probiotic. The treatment with DA substantially reduced the weight % of crucial enamel minerals, i.e., Ca and P. Notably, the probiotic was able to reverse the demineralization process, bringing Ca and P weight % back to basal levels, including the Ca/P ratio. Conclusions. The findings indicate that L. brevis is able to efficiently protect the dental enamel surface from the damage caused by DA and increase the enamel resistance to demineralization. Overall, L. brevis confirms its efficacy in preventing or counteracting the action of carious lesions through a novel mechanism that protects the tooth surface under a chemical challenge that mimics the caries process.
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(This article belongs to the Special Issue Role of Probiotics in Health and Disease)
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Hydrogels with Ultrasound-Treated Hyaluronic Acid Regulate CD44-Mediated Angiogenic Potential of Human Vascular Endothelial Cells In Vitro
by
Kelum Chamara Manoj Lakmal Elvitigala, Wildan Mubarok and Shinji Sakai
Biomolecules 2024, 14(5), 604; https://doi.org/10.3390/biom14050604 - 20 May 2024
Abstract
The development of hydrogels that allow vascular endothelial cells to form capillary-like networks is critical for advancing tissue engineering and drug discovery. In this study, we developed hydrogels composed of phenolated hyaluronic acid (HA-Ph) with an average molecular weight of 490–159 kDa via
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The development of hydrogels that allow vascular endothelial cells to form capillary-like networks is critical for advancing tissue engineering and drug discovery. In this study, we developed hydrogels composed of phenolated hyaluronic acid (HA-Ph) with an average molecular weight of 490–159 kDa via sonication in an aqueous solution. These hydrogels were synthesized by the horseradish peroxidase-catalyzed crosslinking of phenol moieties in the presence of hydrogen peroxide and phenolated gelatin. The sonication-degraded HA-Ph (198 kDa) significantly enhanced the migration ability of human umbilical vein endothelial cells (HUVECs) on cell culture plates when added to the medium compared to the original HA-Ph (490 kDa) and less-degraded HA-Ph (312–399 kDa). In addition, HUVECs cultured on these hydrogels formed networks that did not occur on hydrogels made from the original HA-Ph. CD44 expression and PI3K gene expression, both markers related to angiogenesis, were 3.5- and 1.8-fold higher, respectively, in cells cultured on sonication-degraded HA-Ph hydrogels than in those cultured on hydrogels comprising the original HA-Ph. These results highlight the potential of hydrogels containing sonication-degraded HA-Ph for tissue engineering and drug-screening applications involving human vascular endothelial cells.
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(This article belongs to the Collection Feature Papers in 'Biological and Bio- Materials' Section)
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Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection
by
Blanca Salgado, Beatriz Izquierdo, Alba Zapata, Isabel Sastre, Henrike Kristen, Julia Terreros, Víctor Mejías, María J. Bullido and Jesús Aldudo
Biomolecules 2024, 14(5), 603; https://doi.org/10.3390/biom14050603 - 20 May 2024
Abstract
Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our
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Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infection, underscoring the importance of cellular cholesterol levels, not only in the viral entry process but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellular accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.
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(This article belongs to the Special Issue Advances in Biomarkers for Neurodegenerative Diseases)
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Accounting for NAD Concentrations in Genome-Scale Metabolic Models Captures Important Metabolic Alterations in NAD-Depleted Systems
by
Roland Sauter, Suraj Sharma and Ines Heiland
Biomolecules 2024, 14(5), 602; https://doi.org/10.3390/biom14050602 - 20 May 2024
Abstract
Nicotinamide adenine dinucleotide (NAD) is a ubiquitous molecule found within all cells, acting as a crucial coenzyme in numerous metabolic reactions. It plays a vital role in energy metabolism, cellular signaling, and DNA repair. Notably, NAD levels decline naturally with age, and this
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Nicotinamide adenine dinucleotide (NAD) is a ubiquitous molecule found within all cells, acting as a crucial coenzyme in numerous metabolic reactions. It plays a vital role in energy metabolism, cellular signaling, and DNA repair. Notably, NAD levels decline naturally with age, and this decline is associated with the development of various age-related diseases. Despite this established link, current genome-scale metabolic models, which offer powerful tools for understanding cellular metabolism, do not account for the dynamic changes in NAD concentration. This impedes our understanding of a fluctuating NAD level’s impact on cellular metabolism and its contribution to age-related pathologies. To bridge this gap in our knowledge, we have devised a novel method that integrates altered NAD concentration into genome-scale models of human metabolism. This approach allows us to accurately reflect the changes in fatty acid metabolism, glycolysis, and oxidative phosphorylation observed experimentally in an engineered human cell line with a compromised level of subcellular NAD.
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(This article belongs to the Special Issue NAD Metabolism in Physiology and Pathology)
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Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer
by
Ziyi Zhao, Jiandong Wang, Weimin Kong, Meredith A. Newton, Wesley C. Burkett, Wenchuan Sun, Lindsey Buckingham, Jillian O’Donnell, Hongyan Suo, Boer Deng, Xiaochang Shen, Xin Zhang, Tianran Hao, Chunxiao Zhou and Victoria L. Bae-Jump
Biomolecules 2024, 14(5), 601; https://doi.org/10.3390/biom14050601 - 20 May 2024
Abstract
Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here, we reported that palmitic acid significantly inhibited cell
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Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here, we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effectively reversed the effects of palmitic acid on cell proliferation, apoptosis, and invasive capacity in endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation and invasion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer.
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(This article belongs to the Special Issue Molecular and Cell Biology in Endometriosis and Endometrial Cancer)
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