International Journal of Molecular Sciences

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International Journal of Molecular Sciences

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8.1

4.9 Journals IJMS

Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches

The Relationship between Circadian Rhythm and Cancer Disease

Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells

Molecularly Imprinted Drug Carrier for Lamotrigine—Design, Synthesis, and Characterization of Physicochemical Parameters

Radiocarbon Flux Measurements Provide Insight into Why a Pyroligneous Acid Product Stimulates Plant Growth Journal Description International Journal of Molecular Sciences International Journal of Molecular Sciences is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and is published semimonthly online by MDPI. The Australian Society of Plant Scientists (ASPS), Epigenetics Society, European Calcium Society (ECS), European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount 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, PMC, MEDLINE, Embase, CAPlus / SciFinder, and other databases. Journal Rank: JCR - Q1 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry) Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.1 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2024). 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. Testimonials: See what our editors and authors say about the IJMS. Companion journals for IJMS include: Biophysica, Obesities, Stresses, Lymphatics and SynBio. Impact Factor: 4.9 (2023); 5-Year Impact Factor: 5.6 (2023) subject Imprint Information get_app Journal Flyer Open Access ISSN: 1422-0067 Latest Articles attachment Supplementary material: Supplementary File 1 (ZIP, 354 KiB) 14 pages, 3859 KiB Open AccessArticle Pervaporation Dehydration Mechanism and Performance of High-Aluminum ZSM-5 Zeolite Membranes for Organic Solvents by Qing Wang, Cheng Qian, Changxu Guo, Nong Xu, Qiao Liu, Bin Wang, Long Fan and Kunhong Hu Int. J. Mol. Sci. 2024, 25(14), 7723; https://doi.org/10.3390/ijms25147723 (registering DOI) - 14 Jul 2024 Abstract Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) [...] Read more. Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption–diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures. Full article (This article belongs to the Topic Membrane Separation Technology Research) 18 pages, 757 KiB Open AccessReview The Utility of Lipidomic Analysis in Colorectal Cancer Diagnosis and Prognosis—A Systematic Review of Recent Literature by Jakub Klekowski, Mariusz Chabowski, Małgorzata Krzystek-Korpacka and Mariusz Fleszar Int. J. Mol. Sci. 2024, 25(14), 7722; https://doi.org/10.3390/ijms25147722 (registering DOI) - 14 Jul 2024 Abstract Colorectal cancer (CRC) is among the most prevalent and lethal malignancies. Lipidomic investigations have revealed numerous disruptions in lipid profiles across various cancers. Studies on CRC exhibit potential for identifying novel diagnostic or prognostic indicators through lipidomic signatures. This review examines recent literature [...] Read more. Colorectal cancer (CRC) is among the most prevalent and lethal malignancies. Lipidomic investigations have revealed numerous disruptions in lipid profiles across various cancers. Studies on CRC exhibit potential for identifying novel diagnostic or prognostic indicators through lipidomic signatures. This review examines recent literature regarding lipidomic markers for CRC. PubMed database was searched for eligible articles concerning lipidomic biomarkers of CRC. After selection, 36 articles were included in the review. Several studies endeavor to establish sets of lipid biomarkers that demonstrate promising potential to diagnose CRC based on blood samples. Phosphatidylcholine, phosphatidylethanolamine, ceramides, and triacylglycerols (TAGs) appear to offer the highest diagnostic accuracy. In tissues, lysophospholipids, ceramides, and TAGs were among the most altered lipids, while unsaturated fatty acids also emerged as potential biomarkers. In-depth analysis requires both cell culture and animal studies. CRC involves multiple lipid metabolism alterations. Although numerous lipid species have been suggested as potential diagnostic markers, the establishment of standardized methods and the conduct of large-scale studies are necessary to facilitate their clinical application. Full article (This article belongs to the Special Issue Colorectal Cancers: An Update on Their Molecular Pathology and Therapy) ►▼ Show Figures

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16 pages, 2454 KiB Open AccessArticle Effects of Age and MPTP-Induced Parkinson’s Disease on the Expression of Genes Associated with the Regulation of the Sleep–Wake Cycle in Mice by Ekaterina I. Semenova, Margarita M. Rudenok, Ivan N. Rybolovlev, Marina V. Shulskaya, Maria V. Lukashevich, Suzanna A. Partevian, Alexander I. Budko, Maxim S. Nesterov, Denis A. Abaimov, Petr A. Slominsky, Maria I. Shadrina and Anelya Kh. Alieva Int. J. Mol. Sci. 2024, 25(14), 7721; https://doi.org/10.3390/ijms25147721 (registering DOI) - 14 Jul 2024 Abstract Parkinson’s disease (PD) is characterized by a long prodromal period, during which patients often have sleep disturbances. The histaminergic system and circadian rhythms play an important role in the regulation of the sleep–wake cycle. Changes in the functioning of these systems may be [...] Read more. Parkinson’s disease (PD) is characterized by a long prodromal period, during which patients often have sleep disturbances. The histaminergic system and circadian rhythms play an important role in the regulation of the sleep–wake cycle. Changes in the functioning of these systems may be involved in the pathogenesis of early stages of PD and may be age-dependent. Here, we have analyzed changes in the expression of genes associated with the regulation of the sleep–wake cycle (Hnmt, Hrh1, Hrh3, Per1, Per2, and Chrm3) in the substantia nigra (SN) and striatum of normal male mice of different ages, as well as in young and adult male mice with an MPTP-induced model of the early symptomatic stage (ESS) of PD. Age-dependent expression analysis in normal mouse brain tissue revealed changes in Hrh3, Per1, Per2, and Chrm3 genes in adult mice relative to young mice. When gene expression was examined in mice with the MPTP-induced model of the ESS of PD, changes in the expression of all studied genes were found only in the SN of adult mice with the ESS model of PD. These data suggest that age is a significant factor influencing changes in the expression of genes associated with sleep–wake cycle regulation in the development of PD. Full article (This article belongs to the Special Issue Neuropathological Features of Aging and Neurodegenerative Diseases) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 285 KiB) 18 pages, 16516 KiB Open AccessArticle Therapeutic Effect of Lecigel, Cetiol®CC, Activonol-6, Activonol-M, 1,3-Propanediol, Soline, and Fucocert® (LCAA-PSF) Treatment on Imiquimod-Induced Psoriasis-Like Skin in Mice by Chih-Ching Li, Chih-Chien Lin, Chun-Yi Lee, Meei-Ling Sheu, Yi-Ching Tsai, Chia-Yun Tsai, Hao-Ting Wu, Ren-Jang Wu and De-Wei Lai Int. J. Mol. Sci. 2024, 25(14), 7720; https://doi.org/10.3390/ijms25147720 (registering DOI) - 14 Jul 2024 Abstract The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination [...] Read more. The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFβ, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFβ-related signal pathway. Full article (This article belongs to the Special Issue Molecular and Cellular Mechanisms of Skin Diseases) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 102 KiB) 21 pages, 10213 KiB Open AccessArticle Low-Temperature Regulates the Cell Structure and Chlorophyll in Addition to Cellulose Metabolism of Postharvest Red Toona sinensis Buds across Different Seasons by Qian Zhao, Fu Wang, Yifei Wang, Xiulai Zhong, Shunhua Zhu, Xinqi Zhang, Shuyao Li, Xiujuan Lei, Zhenyuan Zang, Guofei Tan and Jian Zhang Int. J. Mol. Sci. 2024, 25(14), 7719; https://doi.org/10.3390/ijms25147719 (registering DOI) - 14 Jul 2024 Abstract Postharvest fibrosis and greening of Toona sinensis buds significantly affect their quality during storage. This study aimed to clarify the effects of low-temperature storage on postharvest red TSB quality harvested in different seasons. Red TSB samples were collected from Guizhou province, China, 21 [...] Read more. Postharvest fibrosis and greening of Toona sinensis buds significantly affect their quality during storage. This study aimed to clarify the effects of low-temperature storage on postharvest red TSB quality harvested in different seasons. Red TSB samples were collected from Guizhou province, China, 21 days after the beginning of spring (Lichun), summer (Lixia), and autumn (Liqiu), and stored at 4 °C in dark conditions. We compared and analyzed the appearance, microstructure, chlorophyll and cellulose content, and expression levels of related genes across different seasons. The results indicated that TSB harvested in spring had a bright, purple-red color, whereas those harvested in summer and autumn were green. All samples lost water and darkened after 1 day of storage. Severe greening occurred in spring-harvested TSB within 3 days, a phenomenon not observed in summer and autumn samples. Microstructural analysis revealed that the cells in the palisade and spongy tissues of spring and autumn TSB settled closely during storage, while summer TSB cells remained loosely aligned. Xylem cells were smallest in spring-harvested TSB and largest in autumn. Prolonged storage led to thickening of the secondary cell walls and pith cell autolysis in the petioles, enlarging the cavity area. Chlorophyll content was higher in leaves than in petioles, while cellulose content was lower in petioles across all seasons. Both chlorophyll and cellulose content increased with storage time. Gene expression analysis showed season-dependent variations and significant increases in the expression of over half of the chlorophyll-related and cellulose-related genes during refrigeration, correlating with the observed changes in chlorophyll and cellulose content. This research provides valuable insights for improving postharvest storage and freshness preservation strategies for red TSB across different seasons. Full article (This article belongs to the Special Issue New Insights into Environmental Stresses and Plants) ►▼ Show Figures

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14 pages, 1008 KiB Open AccessArticle Itch and Pain Behaviors in Irritant Contact Dermatitis Produced by Sodium Lauryl Sulfate in Mice by Nathalie M. Malewicz-Oeck, Zhe Zhang, Steven G. Shimada and Robert H. LaMotte Int. J. Mol. Sci. 2024, 25(14), 7718; https://doi.org/10.3390/ijms25147718 (registering DOI) - 14 Jul 2024 Abstract Irritant contact dermatitis (ICD) is a nonspecific skin inflammation caused by irritants, leading to itch and pain. We tested whether differential responses to histamine-dependent and -independent pruritogens can be evoked in ICD induced by sodium lauryl sulfate (SLS). An ICD mouse model was [...] Read more. Irritant contact dermatitis (ICD) is a nonspecific skin inflammation caused by irritants, leading to itch and pain. We tested whether differential responses to histamine-dependent and -independent pruritogens can be evoked in ICD induced by sodium lauryl sulfate (SLS). An ICD mouse model was established with 5% SLS in acetone versus a vehicle topically applied for 24 h to the cheek. Site-directed itch- and pain-like behaviors, occurring spontaneously and in response to mechanical, thermal, and chemical stimuli (histamine, ß-alanine, BAM8-22, and bradykinin) applied to the cheek, were recorded before (day 0) and after irritant removal (days 1, 2, 3, and 4). Skin inflammation was assessed through visual scoring, ultrasound, and measurements of skin thickness. SLS-treated mice exhibited hyperalgesia-like behavior in response to mechanical and heat stimuli on day 1 compared to the controls. SLS mice exhibited more spontaneous wipes (pain) but not scratching bouts (itch) on day 1. Pruritogen injections caused more scratching but not wiping in SLS-treated mice compared to the controls. Only bradykinin increased wiping behavior compared to saline. SLS-treated mice developed noticeable erythema, scaling, and increased skin thickness on days 1 and 2. SLS induced cutaneous inflammation and behavioral signs of spontaneous pain and itching, hyperalgesia to mechanical and heat stimuli and a chemical algogen, and enhanced itch response to pruritogens. These sensory reactions preceded the inflammation peak and lasted up to two days. Full article (This article belongs to the Section Molecular Immunology) 20 pages, 985 KiB Open AccessReview Fatty Acid-Binding Protein 4-Mediated Regulation Is Pivotally Involved in Retinal Pathophysiology: A Review by Hiroshi Ohguro, Megumi Watanabe, Fumihito Hikage, Tatsuya Sato, Nami Nishikiori, Araya Umetsu, Megumi Higashide, Toshifumi Ogawa and Masato Furuhashi Int. J. Mol. Sci. 2024, 25(14), 7717; https://doi.org/10.3390/ijms25147717 (registering DOI) - 14 Jul 2024 Abstract Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member [...] Read more. Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member of this family of proteins that are expressed in adipocytes and macrophages, plays pivotal roles in the pathogenesis of various cardiovascular and metabolic diseases, including diabetes mellitus (DM) and hypertension (HT). Since significant increases in the serum levels of FABP4 were detected in those patients, FABP4 has been identified as a crucial biomarker for these systemic diseases. In addition, in the field of ophthalmology, our group found that intraocular levels of FABP4 (ioFABP4) and free fatty acids (ioFFA) were substantially elevated in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), for which DM and HT are also recognized as significant risk factors. Recent studies have also revealed that ioFABP4 plays important roles in both retinal physiology and pathogenesis, and the results of these studies have suggested potential molecular targets for retinal diseases that might lead to future new therapeutic strategies. Full article (This article belongs to the Special Issue Cell Signaling and Molecular Pathology of Retinal Diseases : 2nd Edition) attachment Supplementary material: Supplementary File 1 (ZIP, 282 KiB) 14 pages, 2493 KiB Open AccessArticle Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance by Karla G. Hernández-Gómez, Laura A. Velázquez-Villegas, Omar Granados-Portillo, Azalia Avila-Nava, Luis E. González-Salazar, Aurora E. Serralde-Zúñiga, Berenice Palacios-González, Edgar Pichardo-Ontiveros, Rocio Guizar-Heredia, Adriana M. López-Barradas, Mónica Sánchez-Tapia, Violeta Larios-Serrato, Viridiana Olin-Sandoval, Andrea Díaz-Villaseñor, Isabel Medina-Vera, Lilia G. Noriega, Gabriela Alemán-Escondrillas, Victor M. Ortiz-Ortega, Nimbe Torres, Armando R. Tovar and Martha Guevara-Cruzadd Show full author list remove Hide full author list Int. J. Mol. Sci. 2024, 25(14), 7716; https://doi.org/10.3390/ijms25147716 (registering DOI) - 14 Jul 2024 Abstract The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the [...] Read more. The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR. Full article (This article belongs to the Special Issue Role of MicroRNAs in Human Diseases) ►▼ Show Figures

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26 pages, 5180 KiB Open AccessReview Mesenchymal Stem Cell-Derived Exosomes as Drug Delivery Vehicles in Disease Therapy by Wenzhe Zhao, Kaixuan Li, Liangbo Li, Ruichen Wang, Yang Lei, Hui Yang and Leming Sun Int. J. Mol. Sci. 2024, 25(14), 7715; https://doi.org/10.3390/ijms25147715 (registering DOI) - 14 Jul 2024 Abstract Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing [...] Read more. Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing side effects. Mesenchymal stem cells (MSCs) are a class of stem cells widely used for tissue engineering, regenerative medicine, and immunotherapy. Exosomes derived from MSCs have special immunomodulatory functions, low immunogenicity, the ability to penetrate tumor tissues, and high yield, which are expected to be engineered into efficient drug delivery systems. Despite the promising promise of MSC-derived exosomes, exploring their optimal preparation methods, drug-loading modalities, and therapeutic potential remains challenging. Therefore, this article reviews the related characteristics, preparation methods, application, and potential risks of MSC-derived exosomes as drug delivery systems in order to find potential therapeutic breakthroughs. Full article (This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine: 2nd Edition) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 141 KiB) 15 pages, 1475 KiB Open AccessArticle Promoter of Cassava MeAHL31 Responds to Diverse Abiotic Stresses and Hormone Signals in Transgenic Arabidopsis by Xiao-Tong Wang, Xiang-Ning Tang, Ya-Wen Zhang, Yu-Qiang Guo, Yuan Yao, Rui-Mei Li, Ya-Jie Wang, Jiao Liu and Jian-Chun Guo Int. J. Mol. Sci. 2024, 25(14), 7714; https://doi.org/10.3390/ijms25147714 (registering DOI) - 14 Jul 2024 Abstract The AT-hook motif nuclear-localized (AHL) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress [...] Read more. The AT-hook motif nuclear-localized (AHL) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis-acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal. Full article (This article belongs to the Section Molecular Plant Sciences) attachment Supplementary material: Supplementary File 1 (ZIP, 379 KiB) 23 pages, 4091 KiB Open AccessArticle Grape Seed Proanthocyanidin Extract Attenuates Cafeteria-Diet-Induced Liver Metabolic Disturbances in Rats: Influence of Photoperiod by Romina M. Rodríguez, Marina Colom-Pellicer, Julia Hernández-Baixauli, Enrique Calvo, Manuel Suárez, Anna Arola-Arnal, Cristina Torres-Fuentes, Gerard Aragonès and Miquel Mulero Int. J. Mol. Sci. 2024, 25(14), 7713; https://doi.org/10.3390/ijms25147713 (registering DOI) - 14 Jul 2024 Abstract This study investigated the influence of photoperiod (day length) on the efficacy of grape seed proanthocyanidin extract (GSPE) in mitigating metabolic disorders in obese rats fed a cafeteria diet. Rats were exposed to standard (L12), long (L18), or short (L6) photoperiods and treated [...] Read more. This study investigated the influence of photoperiod (day length) on the efficacy of grape seed proanthocyanidin extract (GSPE) in mitigating metabolic disorders in obese rats fed a cafeteria diet. Rats were exposed to standard (L12), long (L18), or short (L6) photoperiods and treated with GSPE or vehicle. In the standard photoperiod, GSPE reduced body weight gain (50.5%), total cholesterol (37%), and triglycerides (34.8%), while increasing the expression of hepatic metabolic genes. In the long photoperiod, GSPE tended to decrease body weight gain, increased testosterone levels (68.3%), decreased liver weight (12.4%), and decreased reverse serum amino acids. In the short photoperiod, GSPE reduced glycemia (~10%) and lowered triglyceride levels (38.5%), with effects modified by diet. The standard photoperiod showed the greatest efficacy against metabolic syndrome-associated diseases. The study showed how day length affects GSPE’s benefits and underscores considering biological rhythms in metabolic disease therapies. Full article (This article belongs to the Special Issue Lipid Molecules in Inflammation and Chronic Diseases 2.0) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 859 KiB) 22 pages, 6209 KiB Open AccessArticle Functional Characterisation of Surfactant Protein A as a Novel Prophylactic Means against Oncogenic HPV Infections by Sinead Carse, Tim Reid, Jens Madsen, Howard Clark, Artur Kirjakulov, Martina Bergant Marušič and Georgia Schäfer Int. J. Mol. Sci. 2024, 25(14), 7712; https://doi.org/10.3390/ijms25147712 (registering DOI) - 14 Jul 2024 Abstract Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule [...] Read more. Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A’s suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A’s ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types. Full article (This article belongs to the Special Issue Viral Infections and Host Immune Responses) ►▼ Show Figures

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35 pages, 541 KiB Open AccessReview The Off-Target Cardioprotective Mechanisms of Sodium–Glucose Cotransporter 2 Inhibitors: An Overview by Loredana N. Ionică, Adina V. Lința, Alina D. Bătrîn, Iasmina M. Hâncu, Bogdan M. Lolescu, Maria D. Dănilă, Lucian Petrescu, Ioana M. Mozoș, Adrian Sturza and Danina M. Muntean Int. J. Mol. Sci. 2024, 25(14), 7711; https://doi.org/10.3390/ijms25147711 (registering DOI) - 14 Jul 2024 Abstract Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a novel class of glucose-lowering drugs, have revolutionized the management of heart failure with reduced and preserved ejection fraction, regardless of the presence of diabetes, and are currently incorporated in the heart failure guidelines. While these drugs have [...] Read more. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a novel class of glucose-lowering drugs, have revolutionized the management of heart failure with reduced and preserved ejection fraction, regardless of the presence of diabetes, and are currently incorporated in the heart failure guidelines. While these drugs have consistently demonstrated their ability to decrease heart failure hospitalizations in several landmark clinical trials, their cardioprotective effects are far from having been completely elucidated. In the past decade, a growing body of experimental research has sought to address the molecular and cellular mechanisms of SGLT2i in order to provide a better understanding of the off-target acute and chronic cardiac benefits, beyond the on-target renal effect responsible for blood glucose reduction. The present narrative review addresses the direct cardioprotective effects of SGLT2i, delving into the off-target mechanisms of the drugs currently approved for heart failure therapy, and provides insights into future perspectives. Full article (This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cardiovascular and Metabolic Diseases 2.0) 20 pages, 3698 KiB Open AccessReview Curcumin and Gut Microbiota: A Narrative Overview with Focus on Glycemic Control by Simona Servida, Alessandra Piontini, Francesca Gori, Laura Tomaino, Gianluca Moroncini, Vito De Gennaro Colonna, Carlo La Vecchia and Luisella Vigna Int. J. Mol. Sci. 2024, 25(14), 7710; https://doi.org/10.3390/ijms25147710 (registering DOI) - 14 Jul 2024 Abstract Turmeric is a spice widely used in China, Southeast Asia, and in traditional Ayurvedic medicine. Its safety profile and efficacy as an antioxidant, anti-inflammatory, antimicrobial, antitumor, antidiabetic, and anti-obesity agent have led to extensive research into its potential role in preventing and treating [...] Read more. Turmeric is a spice widely used in China, Southeast Asia, and in traditional Ayurvedic medicine. Its safety profile and efficacy as an antioxidant, anti-inflammatory, antimicrobial, antitumor, antidiabetic, and anti-obesity agent have led to extensive research into its potential role in preventing and treating metabolic diseases. The active compound in turmeric is curcumin, which exhibits low systemic bioavailability after oral administration. However, it is detectable in the gut, where it bidirectionally interacts with the gut microbiota (GM), which plays a crucial role in maintaining host health. The favorable effects of curcumin, particularly its hypoglycemic properties, are linked to alteration in intestinal dysbiosis observed in type 2 diabetes mellitus and metabolic syndrome patients. Restoration of the eubiotic GM may contribute to glycemic homeostasis. Preclinical and clinical studies have demonstrated the involvement of the GM in the regulation of glucose and lipid metabolism. Although the underlying mechanism remains incompletely understood, intestinal dysbiosis is associated with insulin resistance, hyperglycemia, and low-grade inflammation. In the present overview, we summarize the biological properties of curcumin, focusing on its link with GM and, therefore, on its potential role in metabolic diseases. Full article (This article belongs to the Special Issue Health Benefits of Curcumin) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 79 KiB) 16 pages, 5952 KiB Open AccessArticle Gastrodin Improves the Activity of the Ubiquitin–Proteasome System and the Autophagy–Lysosome Pathway to Degrade Mutant Huntingtin by He Sun, Miao Li, Yunling Li, Na Zheng, Jiaxin Li, Xiang Li, Yingying Liu, Qianyun Ji, Liping Zhou, Jingwen Su, Wanxu Huang, Zhongbo Liu, Peng Liu and Libo Zou Int. J. Mol. Sci. 2024, 25(14), 7709; https://doi.org/10.3390/ijms25147709 (registering DOI) - 14 Jul 2024 Abstract Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called “Tianma” in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a [...] Read more. Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called “Tianma” in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington’s disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1–100 μM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24–48 h of incubation. The ubiquitin–proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 μM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy–lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose–response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD. Full article (This article belongs to the Special Issue Molecular Mechanisms and Treatments in Neurodegenerative Diseases) ►▼ Show Figures

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22 pages, 5975 KiB Open AccessArticle Optimization of Four Different Rosemary Extraction Techniques Using Plackett–Burman Design and Comparison of Their Antioxidant Compounds by Vassilis Athanasiadis, Theodoros Chatzimitakos, Martha Mantiniotou, Dimitrios Kalompatsios, Konstantina Kotsou, Ioannis Makrygiannis, Eleni Bozinou and Stavros I. Lalas Int. J. Mol. Sci. 2024, 25(14), 7708; https://doi.org/10.3390/ijms25147708 (registering DOI) - 14 Jul 2024 Abstract Rosemary has many medicinal and therapeutic properties and therefore it is important to study how to maximize the recovery of its bioactive compounds. In the present study, four different extraction techniques were used, namely stirring extraction (STE), pulsed electric field-assisted extraction (PEF), ultrasound [...] Read more. Rosemary has many medicinal and therapeutic properties and therefore it is important to study how to maximize the recovery of its bioactive compounds. In the present study, four different extraction techniques were used, namely stirring extraction (STE), pulsed electric field-assisted extraction (PEF), ultrasound probe-assisted extraction (UPAE), and ultrasound bath-assisted extraction (UBAE). First, some primary experiments were carried out in order to optimize each technique individually through the Plackett–Burman design. Then, each technique was applied under optimal conditions and the results were compared with each other. The optimal total polyphenol content (TPC) of STE is ~19 mg gallic acid equivalents per gram of dry weight (dw), while the antioxidant activity of the extract is 162 μmol ascorbic acid equivalents (AAEs) per gram of dw via FRAP and ~110 μmol AAE per gram of dw via DPPH. As for PEF, the optimal TPC is ~12 mg GAE/g dw, and the FRAP and DPPH values are ~102 and ~70 μmol AAE per gram of dw, respectively. When it comes to UPAE, the optimal TPC is ~16 mg GAE/g dw and the antioxidant capacity of the extract is ~128 μmol AAE/g dw through FRAP and ~98 μmol AAE/g dw through DPPH. UBAE optimal extract yielded ~17 mg GAE/g dw TPC, ~146 μmol AAE/g dw for FRAP, and ~143 μmol AAE/g dw for DPPH. The highest flavonoid content (~6.5 mg rutin equivalent/g dw) and DPPH (~143 μmol ascorbic acid equivalent/g dw) is obtained through UBAE. UPAE has been shown to be more efficient in recovering ascorbic acid (~20 mg/g dw). Additionally, the chlorophyll-to-carotenoid ratios of UPAE and UBAE were 2.98 and 2.96, respectively, indicating that the extracts had a generally positive impact on health. Considering the environmental impact of each extraction technique but also which antioxidant factor needs to be maximized, the most suitable extraction technique will be chosen. Full article (This article belongs to the Special Issue Insights into Antioxidant Compounds: From Extraction to Mechanism of Action) ►▼ Show Figures

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20 pages, 10553 KiB Open AccessArticle A Study on the Functional Identification of Overexpressing Winter Wheat Expansin Gene TaEXPA7-B in Rice under Salt Stress by Xue Wang, Jing Ma, Fumeng He, Linlin Wang, Tong Zhang, Dan Liu, Yongqing Xu, Fenglan Li and Xu Feng Int. J. Mol. Sci. 2024, 25(14), 7707; https://doi.org/10.3390/ijms25147707 (registering DOI) - 14 Jul 2024 Abstract Expansin is a cell wall relaxant protein that is common in plants and directly or indirectly participates in the whole process of plant root growth, development and morphogenesis. A well-developed root system helps plants to better absorb water and nutrients from the soil [...] Read more. Expansin is a cell wall relaxant protein that is common in plants and directly or indirectly participates in the whole process of plant root growth, development and morphogenesis. A well-developed root system helps plants to better absorb water and nutrients from the soil while effectively assisting them in resisting osmotic stress, such as salt stress. In this study, we observed and quantified the morphology of the roots of Arabidopsis overexpressing the TaEXPAs gene obtained by the research group in the early stage of development. We combined the bioinformatics analysis results relating to EXPA genes in five plants and identified TaEXPA7-B, a member of the EXPA family closely related to root development in winter wheat. Subcellular localization analysis of the TaEXPA7-B protein showed that it is located in the plant cell wall. In this study, the TaEXPA7-B gene was overexpressed in rice. The results showed that plant height, root length and the number of lateral roots of rice overexpressing the TaEXPA7-B gene were significantly higher than those of the wild type, and the expression of the TaEXPA7-B gene significantly promoted the growth of lateral root primordium and cortical cells. The plants were treated with 250 mM NaCl solution to simulate salt stress. The results showed that the accumulation of osmotic regulators, cell wall-related substances and the antioxidant enzyme activities of the overexpressed plants were higher than those of the wild type, and they had better salt tolerance. This paper discusses the effects of winter wheat expansins in plant root development and salt stress tolerance and provides a theoretical basis and relevant reference for screening high-quality expansin regulating root development and salt stress resistance in winter wheat and its application in crop molecular breeding. Full article (This article belongs to the Section Molecular Genetics and Genomics) ►▼ Show Figures

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attachment Supplementary material: Supplementary File 1 (ZIP, 353 KiB) 12 pages, 3841 KiB Open AccessArticle Genetically Predicted Peripheral Immune Cells Mediate the Effect of Gut Microbiota on Influenza Susceptibility by Shiqi Wang, Guosen Ou, Jialin Wu, Yaokang Chen, Lu Xu and Huachong Xu Int. J. Mol. Sci. 2024, 25(14), 7706; https://doi.org/10.3390/ijms25147706 (registering DOI) - 14 Jul 2024 Abstract The communication mechanism of the gut–lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not [...] Read more. The communication mechanism of the gut–lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut–lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells. Full article (This article belongs to the Special Issue Microbiota’s Role in Respiratory Disorders and Diseases) ►▼ Show Figures

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19 pages, 1786 KiB Open AccessReview Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases by Ranjeet Singh Mahla, Esther L. Jones and Lynn B. Dustin Int. J. Mol. Sci. 2024, 25(14), 7705; https://doi.org/10.3390/ijms25147705 (registering DOI) - 14 Jul 2024 Abstract The Ro60/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including [...] Read more. The Ro60/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including YRNAs (for the ‘y’ in ‘cytoplasmic’), retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal toll-like receptors (TLRs) and cytoplasmic RNA sensors, which typically sense pathogen-associated molecular patterns, and mount the first line of defence against invading pathogens. However, the recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases, including Sjögren’s disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for anti-drug antibody responses among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mechanisms of autoimmune conditions. Full article (This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome 3.0) ►▼ Show Figures

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11 pages, 3388 KiB Open AccessArticle Nordalbergin Synergizes with Novel β-Lactam Antibiotics against MRSA Infection by Haiting Wang, Sangyu Hu, Yuzhu Pei and Hongxiang Sun Int. J. Mol. Sci. 2024, 25(14), 7704; https://doi.org/10.3390/ijms25147704 (registering DOI) - 14 Jul 2024 Abstract The synergetic strategy has created tremendous advantages in drug-resistance bacterial infection treatment, whereas challenges related to novel compound discovery and identifying drug-binding targets still remain. The mechanisms of antimicrobial resistance involving β-lactamase catalysis and the degradation of β-lactam antibiotics are being [...] Read more. The synergetic strategy has created tremendous advantages in drug-resistance bacterial infection treatment, whereas challenges related to novel compound discovery and identifying drug-binding targets still remain. The mechanisms of antimicrobial resistance involving β-lactamase catalysis and the degradation of β-lactam antibiotics are being revealed, with relevant therapies promising to improve the efficacy of existing major classes of antibiotics in the foreseeable future. In this study, it is demonstrated that nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, efficiently potentiated the activities of β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by suppressing β-lactamase performance and improving the bacterial biofilm susceptibility to antibiotics. Nordalbergin was found to destabilize the cell membrane and promote its permeabilization. Moreover, nordalbergin efficiently improved the therapeutic efficacy of amoxicillin against MRSA pneumonia in mice, as supported by the lower bacterial load, attenuated pathological damage, and decreased inflammation level. These results demonstrate that nordalbergin might be a promising synergist of amoxicillin against MRSA infections. This study provided a new approach for developing potentiators for β-lactam antibiotics against MRSA infections. Full article (This article belongs to the Section Bioactives and Nutraceuticals) ►▼ Show Figures