International Journal of Molecular Sciences

16 pages, 1831 KiB

Open AccessArticle

Overexpression of the Transcription Factor GmbZIP60 Increases Salt and Drought Tolerance in Soybean (Glycine max)

by Mengnan Chai, Fan Yang, Shuping Cai, Tingyu Liu, Xiaoyuan Xu, Youmei Huang, Xinpeng Xi, Jiahong Yang, Zhuangyuan Cao, Ling Sun, Danlin Dou, Xunlian Fang, Maokai Yan and Hanyang Cai

Int. J. Mol. Sci. 2025, 26(7), 3455; https://doi.org/10.3390/ijms26073455 - 7 Apr 2025

Viewed by 431

Abstract

The regulation of downstream responsive genes by transcription factors (TFs) is a critical step in the stress response system of plants. While bZIP transcription factors are known to play important roles in stress reactions, their functional characterization in soybeans remains limited. Here, we [...] Read more.

The regulation of downstream responsive genes by transcription factors (TFs) is a critical step in the stress response system of plants. While bZIP transcription factors are known to play important roles in stress reactions, their functional characterization in soybeans remains limited. Here, we identified a soybean bZIP gene, GmbZIP60, which encodes a protein containing a typical bZIP domain with a basic region and a leucine zipper region. Subcellular localization studies confirmed that GmbZIP60 is localized in the nucleus. Expression analysis demonstrated that GmbZIP60 is induced by salt stress, drought stress, and various plant hormone treatments, including abscisic acid (ABA), ethylene (ETH), and methyl jasmonate acid (MeJA). Overexpressing GmbZIP60 (OE-GmbZIP60) in transgenic soybean and rice enhanced tolerance to both salt and drought stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the expression levels of abiotic stress-responsive genes were significantly higher in transgenic plants than in wild-type (WT) plants under stress conditions. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) analysis further confirmed that GmbZIP60 directly binds to the promoters of abiotic stress-related genes induced by ABA, ETH, JA, and salicylic acid (SA). Overall, these findings revealed GmbZIP60 as a positive regulator of salt and drought stress tolerance. Full article

(This article belongs to the Special Issue Plant Response to Drought, Heat, and Light Stress)

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15 pages, 5911 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of GASA Genes in Hevea brasiliensis Reveals Their Involvement in Response to Cold Stress

by Yuying Cong, Yanshi Hu, Zhi Deng, Wenguan Wu, Tingkai Wu, Yanhong Zhao and Zewei An

Int. J. Mol. Sci. 2025, 26(7), 3454; https://doi.org/10.3390/ijms26073454 - 7 Apr 2025

Viewed by 278

Abstract

The Gibberellic Acid Stimulated in Arabidopsis (GASA) gene family is regulated by gibberellins and plays a crucial role in regulating plant growth and development. Based on rubber tree genome data, 18 HbGASA genes, designated HbGASA1 to HbGASA18, were identified in Hevea brasiliensis [...] Read more.

The Gibberellic Acid Stimulated in Arabidopsis (GASA) gene family is regulated by gibberellins and plays a crucial role in regulating plant growth and development. Based on rubber tree genome data, 18 HbGASA genes, designated HbGASA1 to HbGASA18, were identified in Hevea brasiliensis. Comprehensive bioinformatics analyses were performed to characterize gene structures, chromosomal distributions, syntenic relationships, protein architectures, phylogenetic evolution, and expression profiles. The expression patterns of HbGASA genes under low-temperature stress were further validated by quantitative real-time polymerase chain reactions (qRT-PCR). The results demonstrated that the 18 HbGASA genes were unevenly distributed across 10 chromosomes. The encoded proteins ranged from 88 to 253 amino acids in length, and the number of exons varied from 2 to 4. Phylogenetic analysis clustered these genes into three distinct clades. Conserved motif analysis identified 10 conserved motifs, with Motif 1 and Motif 2 being highly conserved across all members. Promoter analysis revealed multiple hormone-responsive and stress-related regulatory cis-acting elements. Transcripts of the 18 HbGASA genes were detected in various tissues, and significant differences were observed in their expression levels. Under cold stress, qRT-PCR results showed that multiple HbGASA genes were significantly up-regulated. This study provides valuable insights into the structure, evolution, and functional diversification of GASA genes in the important tropical crop, H. brasiliensis. Full article

(This article belongs to the Special Issue Genomic Perspective on Forest Genetics and Phytopathobiomes)

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13 pages, 1583 KiB

Open AccessArticle

Genome-Wide Association Studies of Body Weight and Average Daily Gain in Chinese Dongliao Black Pigs

by Min Huang, Wenyu Zhang, Jiangpeng Dong, Zhengyu Hu, Xuhui Tan, Hao Li, Kailing Sun, Ayong Zhao and Tao Huang

Int. J. Mol. Sci. 2025, 26(7), 3453; https://doi.org/10.3390/ijms26073453 - 7 Apr 2025

Viewed by 274

Abstract

In the domain of swine production, body weight (BW) and average daily gain (ADG) are recognized as the primary performance indicators. Nevertheless, the genetic architecture of ADG and BW in Dongliao black (DLB) pigs remains to be fully elucidated. In this study, we [...] Read more.

In the domain of swine production, body weight (BW) and average daily gain (ADG) are recognized as the primary performance indicators. Nevertheless, the genetic architecture of ADG and BW in Dongliao black (DLB) pigs remains to be fully elucidated. In this study, we performed a genome-wide association analysis of BW, ADG, and body mass index (BMI) in 358 DLB pigs of different days of age. The genome-wide association study (GWAS) showed the following: (1) The most significant single nucleotide polymorphism (SNP) detected for BW was on Sus scrofa chromosome (SSC) 11:100,808 (p-value = 1.16 × 10⁻⁶) that was also the most significant SNP for ADG. (2) The most significant SNP associated with BMI was SSC17:51,463,521 (p-value = 5.16 × 10⁻⁸). (3) SNPs SSC10:6,523,844 and SSC17:23,852,682 were identified in both BW and ADG. A meta-analysis was conducted on BW at different days and demonstrated SSC5:39,028,335 (p-value = 8.37 × 10⁻⁶) which was not identified in the results of each single trait. The regions of two SNPs (SSC11:100,808, SSC4:10,703,277) exhibited considerable influence on both BW and ADG and the related regions were selected for linkage disequilibrium (LD) analyses that exhibited a notable linkage. In addition, several genes were identified that are associated with obesity and play roles in lipid metabolism, including MACROD2, PHLPP2, CYP2E1, and STT3B. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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19 pages, 4142 KiB

Open AccessArticle

Development of Sheep Duodenum Intestinal Organoids and Implementation of High-Throughput Screening Platform for Veterinary Applications

by Giulio Galli, Estela Melcón-Fernández, María Gracia de Garnica García, Beatriz Martínez-Fernández, Mahsa Dehnavi, Sonia Andrés, Yolanda Pérez-Pertejo, Rosa M. Reguera, Carlos García-Estrada, María Martínez-Valladares and Rafael Balaña-Fouce

Int. J. Mol. Sci. 2025, 26(7), 3452; https://doi.org/10.3390/ijms26073452 - 7 Apr 2025

Viewed by 358

Abstract

New therapeutic molecules for farm animals are needed to address worldwide problems in the food industry, like the rise of resistance among ruminant parasites and pathogenic microbes. Since in vivo testing would involve an excessive number of animals, with consequent ethical and economic [...] Read more.

New therapeutic molecules for farm animals are needed to address worldwide problems in the food industry, like the rise of resistance among ruminant parasites and pathogenic microbes. Since in vivo testing would involve an excessive number of animals, with consequent ethical and economic issues, the generation of sheep intestinal organoids represents a promising close-to-reality in vitro model for veterinary drug development; however, the characterization and application of such organoids remain limited. In this study, ovine intestinal organoids were generated from adult LGR5+ stem cells from the intestinal crypts of freshly slaughtered lambs, and developed in an in vitro culture system. Morphological analysis via brightfield microscopy and immunocytochemical staining revealed a pseudostratified epithelium with multiple cell types, and distinct apical–basal polarity, while RNA sequencing validated the preservation of the physiological characteristics of the original organ. The development and characterization of a robust and reproducible protocol for culturing sheep duodenum intestinal organoids in a high-throughput screening (HTS) compatible format demonstrated reliability in HTS applications, with Z’-factor tests indicating robust assay performance. Dose–response studies using pre-identified compounds showed comparable pharmacodynamic profiles between mouse and sheep organoids. These findings establish sheep intestinal organoids as an innovative tool for veterinary pharmacology and toxicology, offering a cost-effective and sustainable platform to address challenges such as drug resistance and improve livestock health. Full article

(This article belongs to the Special Issue Intestinal 3D Culture, Organoids and Gut-on-Chip in Intestinal Disorders)

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16 pages, 2853 KiB

Open AccessArticle

Monoclonality and Low Genetic Diversity in Vanilla shenzhenica: Highlighting Urgent Need for Genetic Preservation of China’s Only Endangered Vanilla

by Li Xiao, Ai-Qun Hu, Mei-Na Wang, Zhuo Cheng, Kuan-Bo Chi, Chun-Lin Long and Jin-Gang Liu

Int. J. Mol. Sci. 2025, 26(7), 3451; https://doi.org/10.3390/ijms26073451 - 7 Apr 2025

Viewed by 292

Abstract

Long-term clonality has profound consequences for genetic structure despite offering an alternative means of reproductive assurance under unfavorable conditions for sexual reproduction. Vanilla shenzhenica Z. J. Liu & S. C. Chen (Orchidaceae), the only endangered Vanilla species in China, exhibits a clear tendency [...] Read more.

Long-term clonality has profound consequences for genetic structure despite offering an alternative means of reproductive assurance under unfavorable conditions for sexual reproduction. Vanilla shenzhenica Z. J. Liu & S. C. Chen (Orchidaceae), the only endangered Vanilla species in China, exhibits a clear tendency towards asexual propagation, as evidenced by its small, fragmented wild populations. To develop effective conservation strategies for this species, it is essential to assess the extent of clonality and evaluate genetic diversity both within and among populations. In this study, we sampled 43 individuals from cultivated and wild populations of V. shenzhenica and analyzed their phylogenetic relationships, genetic structure, and diversity based on single-nucleotide polymorphisms (SNPs). Our results indicate that all the studied wild populations are predominantly sustained by vegetative growth, each forming a monoclonal patch with a single genotype. The overall genetic diversity within V. shenzhenica is low likely due to a combination of factors, including clonality, reduced effective population size, and environmental disturbances. These findings underscore the urgent need for the conservation management of this species. Conservation plans should prioritize ex situ conservation efforts, focusing on promoting assisted sexual reproduction to produce viable seeds and offspring that combine diverse genotypes from different populations. This study provides valuable insights in relation to effective conservation planning for endangered clonal species. Full article

(This article belongs to the Special Issue Genomic Perspective on Forest Genetics and Phytopathobiomes)

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20 pages, 443 KiB

Open AccessArticle

Agronomic and Metabolic Responses of Citrus clementina to Long-Term Irrigation with Saline Reclaimed Water as Abiotic Factor

by David Auñón-Calles, María Pinciroli, Emilio Nicolás, Angel Gil-Izquierdo, José Antonio Gabaldón, María Puerto Sánchez-Iglesias, Angel Antonio Carbonell-Barrachina, Federico Ferreres, Carlos J. García and Cristina Romero-Trigueros

Int. J. Mol. Sci. 2025, 26(7), 3450; https://doi.org/10.3390/ijms26073450 - 7 Apr 2025

Viewed by 194

Abstract

The Panel on Climate Change has predicted an intensification of drought and heat waves. The aim of this study was to determine the physiological response of mandarin trees in a semi-arid area to the effects of a long period of irrigation with saline [...] Read more.

The Panel on Climate Change has predicted an intensification of drought and heat waves. The aim of this study was to determine the physiological response of mandarin trees in a semi-arid area to the effects of a long period of irrigation with saline reclaimed water (RW) and freshwater (FW) in terms of leaf mineral constitution, free amino acids and phytohormone balance, and their influence on yield and fruit quality. Results showed that higher foliar levels of Cl⁻_, B, Li⁺, and Br⁻ were found in the RW treatment. In addition, fruit quality (juice content, soluble solid content, titratable acid, and maturity index) and yield (fruit weight and diameter) parameters and growth canopy were negatively affected by irrigation with RW. Regardless of the treatments, L-alanine (Ala) and proline were the most abundant amino acids, with Ala being described as a majority for the first time in the literature. Concretely, in FW, the total amino acid content was twice as high as the concentration in RW (51,359.46 and 23,833.31 ng g⁻¹, respectively). The most abundant hormones were 1-Aminocyclopropane-1-carboxylic acid and trans-zeatin in both treatments. The saline stress response would be reflected in the higher concentration of salicylic and abscisic acids in the leaves of RW trees. In view of the high correlations found in a simplified correlation matrix of (i) Ala with the canopy growth and (ii) the salicylic acid (SA) with most of the evaluated agrometabolic parameters, it can be concluded that the exogenous application of the Ala and SA would increase tree size and could mitigate the effects of salt stress, respectively. However, these treatments could be completed with the external application of ACC since this phytohormone presents the lowest parameter during treatment with RW. Full article

(This article belongs to the Special Issue Molecular Advances in Abiotic Stress Signaling in Plants: Focus on Atmospheric Stressors, 2nd Edition)

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26 pages, 2576 KiB

Open AccessReview

MicroRNAs as Endocrine Modulators of Breast Cancer

by Vinitha Richard, Kevin Lee and Michael Joseph Kerin

Int. J. Mol. Sci. 2025, 26(7), 3449; https://doi.org/10.3390/ijms26073449 - 7 Apr 2025

Viewed by 419

Abstract

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of [...] Read more.

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets. Full article

(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)

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47 pages, 1198 KiB

Open AccessReview

Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome

by Mariana Boulos, Rabia S. Mousa, Nizar Jeries, Elias Simaan, Klode Alam, Bulus Bulus and Nimer Assy

Int. J. Mol. Sci. 2025, 26(7), 3448; https://doi.org/10.3390/ijms26073448 - 7 Apr 2025

Viewed by 348

Abstract

Metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related, with rapidly increasing prevalence globally, driving significant public health concerns. Both conditions share common pathophysiological mechanisms such as insulin resistance (IR), adipose tissue dysfunction, oxidative stress, and gut microbiota dysbiosis, [...] Read more.

Metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related, with rapidly increasing prevalence globally, driving significant public health concerns. Both conditions share common pathophysiological mechanisms such as insulin resistance (IR), adipose tissue dysfunction, oxidative stress, and gut microbiota dysbiosis, which contribute to their co-occurrence and progression. While the clinical implications of this overlap, including increased cardiovascular, renal, and hepatic risk, are well recognized, current diagnostic and therapeutic approaches remain insufficient due to the clinical and individuals’ heterogeneity and complexity of these diseases. This review aims to provide an in-depth exploration of the molecular mechanisms linking MetS and MASLD, identify critical gaps in our understanding, and highlight existing challenges in early detection and treatment. Despite advancements in biomarkers and therapeutic interventions, the need for a comprehensive, integrated approach remains. The review also discusses emerging therapies targeting specific pathways, the potential of precision medicine, and the growing role of artificial intelligence in enhancing research and clinical management. Future research is urgently needed to combine multi-omics data, precision medicine, and novel biomarkers to better understand the complex interactions between MetS and MASLD. Collaborative, multidisciplinary efforts are essential to develop more effective diagnostic tools and therapies to address these diseases on a global scale. Full article

(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease: From Basic Science to Therapy)

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22 pages, 7954 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of Thionin Family in Rice (Oryza sativa) and Functional Characterization of OsTHION15 in Drought Stress and ABA Stress

by Maokai Yan, Mengnan Chai, Chang An, Xiaohu Jiang, Fan Yang, Xunlian Fang, Tingyu Liu, Yunfei Ju, Boping Tang, Hanyang Cai and Yuan Qin

Int. J. Mol. Sci. 2025, 26(7), 3447; https://doi.org/10.3390/ijms26073447 - 7 Apr 2025

Viewed by 330

Abstract

The OsTHION family represents a class of cysteine-rich signal peptides widely recognized for their significant roles in plant disease resistance and immunity. While members of this family are known to be induced under various biotic and abiotic stresses, their responses to environmental stressors [...] Read more.

The OsTHION family represents a class of cysteine-rich signal peptides widely recognized for their significant roles in plant disease resistance and immunity. While members of this family are known to be induced under various biotic and abiotic stresses, their responses to environmental stressors beyond disease resistance remain underexplored. This study investigates the evolution, expression patterns, and functional roles of the OsTHION gene family in rice (Oryza sativa) under diverse stress conditions. Using sequence data from the Phytozome database, we identified 44 OsTHION family members and classified them into four groups based on phylogenetic analysis. Cis-acting element analysis revealed that the promoter regions of OsTHION genes are enriched with regulatory elements associated with light response, hormone signaling, plant growth, and stress responses. The OsTHION genes exhibit complex organ-specific expression patterns, with OsTHION30 and OsTHION36 showing ubiquitous expression, while other members are highly expressed in specific tissues or developmental stages. Under drought, salt, and low-temperature stress, OsTHION genes undergo significant expression changes, underscoring their critical role in plant adaptation to environmental challenges. Notably, OsTHION15 was markedly upregulated under drought stress, and the Osthion15 mutant displayed heightened sensitivity to drought and ABA stress, confirming its pivotal role in stress resistance. RNA sequencing analysis identified many differentially expressed genes (DEGs), primarily enriched in pathways related to ribosomal function and plant hormone signaling, suggesting that OsTHION15 may regulate stress responses through multiple mechanisms. In summary, this study advances our understanding of the OsTHION gene family and highlights its intricate involvement in regulating rice growth, development, and environmental stress responses. These findings offer valuable insights and technical support for crop improvement, with potential applications in enhancing environmental adaptability and yield stability in crops. Full article

(This article belongs to the Special Issue Plant Response to Drought, Heat, and Light Stress)

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25 pages, 5048 KiB

Open AccessReview

Recent Advances in Ex Situ Surface Treatments for Lithium Metal Negative Electrodes in Secondary Batteries

by Paul Maldonado Nogales, Sangyup Lee, Seunga Yang and Soon-Ki Jeong

Int. J. Mol. Sci. 2025, 26(7), 3446; https://doi.org/10.3390/ijms26073446 - 7 Apr 2025

Viewed by 658

Abstract

Lithium metal negative electrodes are pivotal for next-generation batteries because of their exceptionally high theoretical capacity and low redox potential. However, their commercialization is constrained by critical challenges, including dendrite formation, volumetric instability, and the fragility of the solid electrolyte interphase (SEI). In [...] Read more.

Lithium metal negative electrodes are pivotal for next-generation batteries because of their exceptionally high theoretical capacity and low redox potential. However, their commercialization is constrained by critical challenges, including dendrite formation, volumetric instability, and the fragility of the solid electrolyte interphase (SEI). In this context, this review highlights the transformative potential of ex situ surface treatments, which stabilize lithium metal electrodes before cell assembly. Key advancements include inorganic and polymer-based coatings that enhance SEI stability and mitigate dendrite growth, three-dimensional host architectures that manage volumetric changes and improve lithium diffusion, and liquid-phase chemical modifications that enable uniform lithium deposition. These strategies are critically evaluated for their scalability, environmental sustainability, and long-term stability, paying particular attention to cost, complexity, and ecological considerations. In addition, their potential contributions to the development of advanced battery technologies are discussed, providing insights into pathways toward enhanced commercial viability. By synthesizing cutting-edge research and identifying unresolved challenges, this review provides a comprehensive roadmap for advancing safer, more efficient, and more durable lithium metal batteries, thereby bridging the gap between laboratory research and commercial adoption. Full article

(This article belongs to the Special Issue Advanced Electrode and Electrolyte Materials: Molecular Scale Design, Synthesis, Mechanisms and Applications)

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13 pages, 2585 KiB

Open AccessArticle

Effect of Hormonal Treatments on Cannabinoid Content Levels in Female Hemp (Cannabis sativa L.) Inflorescences

by Juyoung Kim, Dong-Gun Kim, Tae Hyun Ha, Woon Ji Kim, Jaihyunk Ryu, Jin-Baek Kim and Sang Hoon Kim

Int. J. Mol. Sci. 2025, 26(7), 3445; https://doi.org/10.3390/ijms26073445 - 7 Apr 2025

Viewed by 302

Abstract

The diverse hormonal treatments applied to hemp (Cannabis sativa L.) carry significant implications for cultivation, and yield optimization across a range of applications, including fiber, seed, oil production, and the enhancement of medicinal compounds. However, there is no evidence concerning the long-term [...] Read more.

The diverse hormonal treatments applied to hemp (Cannabis sativa L.) carry significant implications for cultivation, and yield optimization across a range of applications, including fiber, seed, oil production, and the enhancement of medicinal compounds. However, there is no evidence concerning the long-term consequences of hormonal treatment. To determine the connection between the effects of hormonal treatment and cannabinoid accumulation, hemp plants were treated with γ-aminobutyric acid (GABA), abscisic acid (ABA), and salicylic acid (SA) to investigate their effects on gene expression and cannabinoid content levels in female inflorescences at 3 days and 4 weeks after treatment. The treatments influenced the transcript levels of five key cannabinoid biosynthesis genes, with 1.0 mM GABA significantly increasing OAC, THCAS, and CBCAS transcripts within 48 to 72 h. Additionally, 1.0 mM GABA led to a significant increase in tetrahydrocannabinol content by day three and significant increases in total cannabidiol and cannabinoid by week four. In addition, both ABA and SA induced transient, dose-dependent increases or decreases in gene expressions, but cannabinoid accumulation at 4 weeks showed no significant changes compared to the control. These results provide valuable insights for hormonal application in cultivation and the development of traits that enhance cannabinoid production in cannabis cultivation, which could significantly contribute to optimizing industrial applications. Full article

(This article belongs to the Section Molecular Pharmacology)

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20 pages, 4550 KiB

Open AccessArticle

Multi-Target Protective Effects of Sanghuangporus sanghuang Against 5-Fluorouracil-Induced Intestinal Injury Through Suppression of Inflammation, Oxidative Stress, Epitheli-Al-Mesenchymal Transition, and Tight Junction

by Jaung-Geng Lin, Yu-Wen Sun, Wen-Liang Wu, Wen-Ping Jiang, Fang-Yu Zhung and Guan-Jhong Huang

Int. J. Mol. Sci. 2025, 26(7), 3444; https://doi.org/10.3390/ijms26073444 - 7 Apr 2025

Viewed by 263

Abstract

Sanghuang (Sanghuangporus sanghuang, SS) is a medicinal fungus with multiple pharmacological effects, including antioxidant, anti-inflammatory, immune-boosting, and anti-cancer activities. 5-fluorouracil (5-FU) is a commonly used chemotherapeutic agent for the treatment of colorectal cancer. It primarily exerts its antitumor effect by inhibiting [...] Read more.

Sanghuang (Sanghuangporus sanghuang, SS) is a medicinal fungus with multiple pharmacological effects, including antioxidant, anti-inflammatory, immune-boosting, and anti-cancer activities. 5-fluorouracil (5-FU) is a commonly used chemotherapeutic agent for the treatment of colorectal cancer. It primarily exerts its antitumor effect by inhibiting DNA and RNA synthesis, leading to cell apoptosis. However, it frequently induces adverse effects These issues limit the clinical application of 5-FU. This research aims to determine the potential of SS as a therapeutic agent in reducing 5-FU-induced intestinal mucositis in a mouse model. The results indicated that 5-FU administration significantly increased diarrhea severity, reduced colon length, caused small intestinal villus atrophy, disrupted intestinal architecture, led to insufficient crypt cell proliferation, and resulted in weight loss. It also significantly upregulated inflammatory responses, apoptosis, oxidative stress, and epithelial–mesenchymal transition (EMT) pathways, and disrupted the integrity of intestinal mucosal tight junction, while elevating pro-inflammatory cytokines and reducing antioxidant capacity. However, SS significantly ameliorating alleviating the adverse impacts of the chemotherapeutic agent on the intestinal mucosa. In conclusion, this investigation provides the first evidence of the protective effects of SS on 5-FU-induced mucositis. These findings suggest SS as a potential therapeutic application, offering a promising strategy for reducing the adverse effects of 5-FU chemotherapy and improving the treatment and quality of life for colorectal cancer patients. Full article

(This article belongs to the Special Issue The Role of Bioactive Compounds in Human Health and Disease: 2nd Edition)

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17 pages, 2554 KiB

Open AccessArticle

Merging High-Throughput, Amplicon-Based Second and Third Generation Sequencing Data: An Integrative and Modular Data Analysis Framework for Haplotype Prediction and Output Evaluation

by Sylvia Mink, Christian Attenberger, Yannik Busch, Johanna Kiefer, Wolfgang Peter, Janne Cadamuro, Tim A. Steiert, Andre Franke and Christoph Gassner

Int. J. Mol. Sci. 2025, 26(7), 3443; https://doi.org/10.3390/ijms26073443 - 7 Apr 2025

Viewed by 318

Abstract

Despite providing highly accurate results, the short reads generated by second generation sequencing have major limitations in mapping complex genomic regions. Longer reads can resolve these issues and additionally phase distant variants. The third generation sequencing platform ONT currently achieves the longest sequencing [...] Read more.

Despite providing highly accurate results, the short reads generated by second generation sequencing have major limitations in mapping complex genomic regions. Longer reads can resolve these issues and additionally phase distant variants. The third generation sequencing platform ONT currently achieves the longest sequencing reads but falls short in sequencing accuracy. Additionally, deriving phased haplotypes from amplicon-based NGS data remains a complex and time-consuming task that requires extensive bioinformatic expertise. We constructed an integrative, open-access modular data-analysis framework that allows for automated processing of high-throughput sequencing data from both second (Illumina) and third generation (ONT) sequencing platforms, combining the strengths of both technologies. Variant information is automatically evaluated and color-coded for discrepancies. Haplotypes are listed by frequency. All parts of the framework can be used independently. The framework’s performance was validated using synthetic and tested with real-life data by analyzing partly homologous FUT1/2/3 sequencing data from 400 blood donors. Full article

(This article belongs to the Section Molecular Informatics)

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18 pages, 2670 KiB

Open AccessReview

Recent Advances in Genome Editing and Bioinformatics: Addressing Challenges in Genome Editing Implementation and Genome Sequencing

by Hidemasa Bono

Int. J. Mol. Sci. 2025, 26(7), 3442; https://doi.org/10.3390/ijms26073442 - 7 Apr 2025

Viewed by 391

Abstract

Genome-editing technology has advanced significantly since the 2020 Nobel Prize in Chemistry was awarded for the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). While CRISPR–Cas9 has become widely used in academic research, its social implementation has [...] Read more.

Genome-editing technology has advanced significantly since the 2020 Nobel Prize in Chemistry was awarded for the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). While CRISPR–Cas9 has become widely used in academic research, its social implementation has lagged due to unresolved patent disputes and slower progress in gene function analysis. To address this, new approaches bypassing direct gene function analysis are needed, with bioinformatics and next-generation sequencing (NGS) playing crucial roles. NGS is essential for sequencing the genome of target species, but challenges such as data quality, genome heterogeneity, ploidy, and small individual sizes persist. Despite these issues, advancements in sequencing technologies, like PacBio high-fidelity (HiFi) long reads and high-throughput chromosome conformation capture (Hi-C), have improved genome sequencing. Bioinformatics contributes to genome editing through off-target prediction and target gene selection, both of which require accurate genome sequence information. In this review, I will give updates on the development of genome editing and bioinformatics technologies with a focus on the rapid progress in genome sequencing. Full article

(This article belongs to the Section Molecular Informatics)

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12 pages, 400 KiB

Open AccessArticle

A Large Multicenter Brazilian Case-Control Study Exploring Genetic Variations in Interferon Regulatory Factor 6 and the Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate

by Renato Assis Machado, Daniella Reis Barbosa Martelli, Silvia Regina de Almeida Reis, Luiz Evaristo Ricci Volpato, Rafaela Scariot, Juliana Feltrin-Souza, Ana Lúcia Carrinho Ayroza Rangel, Brazilian Oral Cleft Group, Hercílio Martelli-Júnior and Ricardo D. Coletta

Int. J. Mol. Sci. 2025, 26(7), 3441; https://doi.org/10.3390/ijms26073441 - 7 Apr 2025

Viewed by 277

Abstract

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is strongly associated with both environmental and genetic risk factors, but its genetic underpinnings remain partially known. While variants in interferon regulatory factor 6 (IRF6) are linked to NSCL ± P risk [...] Read more.

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is strongly associated with both environmental and genetic risk factors, but its genetic underpinnings remain partially known. While variants in interferon regulatory factor 6 (IRF6) are linked to NSCL ± P risk in populations from Asia and Europe, studies on the highly admixed Brazilian population are scarce and have produced ambiguous results. This study aimed to investigate the contribution of IRF6 variants to the risk of NSCL ± P. Five tag-single nucleotide polymorphisms (rs599021, rs2073485, rs2235375, rs7552506, and rs642961) were analyzed in a large multicenter cohort composed of 1006 patients with NSCL ± P and 942 healthy controls. Statistical analyses involved multiple logistic regression tests consideration the tri-hybrid genetic origin of the Brazilian population, under a Bonferroni p value correcting for multiple comparisons. The A allele (OR: 1.43, 95% CI: 1.22–1.67, p < 0.0001) and AA genotype (OR: 2.04, 95% CI: 1.46–2.86, p < 0.0001) frequencies of rs642961 were significantly associated with NSCL ± P risk. Stratified analyses indicated that the variant is associated with susceptibility to both nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP). However, the association with NSCLO was primarily observed in patients with high African ancestry, whereas the association with NSCLP was predominantly seen in patients with high European ancestry. No significant associations were found for the other investigated variants. Our results support the notion that the IRF6 rs642961 variant represents a marker of susceptibility to NSCL ± P in the Brazilian population, and that genetic ancestry composition plays a central role in the association with the cleft type. Full article

(This article belongs to the Special Issue Exploring the Genetics and Genomics of Complex Diseases)

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18 pages, 914 KiB

Open AccessReview

Abdominal Aortic Aneurysm and Liver Fibrosis: Clinical Evidence and Molecular Pathomechanisms

by Mohamad Jamalinia, Amedeo Lonardo and Ralf Weiskirchen

Int. J. Mol. Sci. 2025, 26(7), 3440; https://doi.org/10.3390/ijms26073440 - 7 Apr 2025

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Abstract

To stimulate further research, this review summarizes studies linking liver fibrosis with the risk of abdominal aortic aneurysms (AAA). AAA is defined as a permanently weakened and dilated abdominal aorta, which develops due to inflammation of the tunica media, activation of the renin–angiotensin–aldosterone [...] Read more.

To stimulate further research, this review summarizes studies linking liver fibrosis with the risk of abdominal aortic aneurysms (AAA). AAA is defined as a permanently weakened and dilated abdominal aorta, which develops due to inflammation of the tunica media, activation of the renin–angiotensin–aldosterone system, immune system activation, and coagulation disorders. Typically asymptomatic, AAA is often incidentally detected through imaging done for abdominal symptoms or as part of screening programs. AAA follows a variable course and has a mortality rate strongly dependent on age and sex. Risk factors for AAA include age, male sex, ethnicity, family history of AAA, lifestyle habits, arterial hypertension, dyslipidemia, and comorbid atherosclerotic cardiovascular disease. Conversely, individuals with type 2 diabetes, female sex, and certain ethnicities are at a reduced risk of AAA. Liver fibrosis, resulting from chronic liver diseases owing to varying etiologies, is increasingly recognized as a potential contributor to AAA development. Evidence increasingly indicates that metabolic dysfunction-associated steatotic liver disease (MASLD) and other chronic liver conditions may intensify inflammatory pathways shared with AAA, thereby potentially exacerbating AAA progression. This review specifically examines the epidemiology and risk factors associated with the link between AAA and liver fibrosis. It also highlights potential pathomechanisms, including systemic inflammation, oxidative stress, and extracellular matrix remodeling, which may contribute to both conditions. Although these findings underscore significant overlaps in risk profiles, additional research is needed to clarify whether type 2 diabetes, female sex, and certain ethnicities truly confer protection against AAA or if this association is influenced by other confounding variables. Ultimately, addressing these open questions will help guide targeted therapeutic interventions and the identification of novel biomarkers to predict disease progression. Full article

(This article belongs to the Section Molecular Endocrinology and Metabolism)

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22 pages, 12194 KiB

Open AccessArticle

Phylogenetic Analysis and Expression Patterns of Triterpenoid Saponin Biosynthesis Genes in 19 Araliaceae Plants

by Chi Ma, Yu Lin, Junjun Yin, Lijuan Zhu, Jinkai Fang and Dan Zhang

Int. J. Mol. Sci. 2025, 26(7), 3439; https://doi.org/10.3390/ijms26073439 - 7 Apr 2025

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Abstract

The Araliaceae family has significant economic and medicinal value. However, the phylogenetic relationships and the expression patterns of key genes of the active triterpenoid substance within this family are still unclear. In this study, we employed comparative transcriptomics to analyze the transcriptomes of [...] Read more.

The Araliaceae family has significant economic and medicinal value. However, the phylogenetic relationships and the expression patterns of key genes of the active triterpenoid substance within this family are still unclear. In this study, we employed comparative transcriptomics to analyze the transcriptomes of 19 species from 11 genera of Araliaceae, aiming to elucidate the evolutionary history of the family and the expression patterns of key genes in the ginsenoside biosynthesis pathway. Our results divide Araliaceae into two subfamilies: Aralioideae and Hydrocotyloideae. Aralioideae is further classified into three groups: the Aralia–Panax group, the Polyscias–Pseudopanax group, and the Asian Palmate group. PhyloNet analysis reveals that the common ancestor of Panax ginseng, Panax quinquefolius, and Panax japonicus was an allopolyploid, likely resulting from hybridization between Panax notoginseng and Panax pseudoginseng. Additionally, all Aralioideae species underwent the pg-β event, which may be critical for ginsenoside biosynthesis. We discovered that Panax species exhibit distinct expression patterns of key enzyme genes (β-AS, DDS, CYP450, UGTs) compared to other Araliaceae species. These enzyme genes show independent evolutionary lineages in gene trees, suggesting unique functional adaptations that enable Panax species to efficiently synthesize ginsenosides. This study provides a theoretical foundation for the conservation and utilization of Araliaceae germplasm resources. Full article

(This article belongs to the Section Molecular Plant Sciences)

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37 pages, 1374 KiB

Open AccessReview

Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2− Breast Cancer

by Paola Ferrari, Maria Luisa Schiavone, Cristian Scatena and Andrea Nicolini

Int. J. Mol. Sci. 2025, 26(7), 3438; https://doi.org/10.3390/ijms26073438 - 7 Apr 2025

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Abstract

Approximately 70–80% of breast cancers are estrogen receptor-positive (ER+), with 65% of these cases also being progesterone receptor-positive (ER+PR+). In most cases of ER+ advanced breast cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These [...] Read more.

Approximately 70–80% of breast cancers are estrogen receptor-positive (ER+), with 65% of these cases also being progesterone receptor-positive (ER+PR+). In most cases of ER+ advanced breast cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These include tamoxifen, a selective estrogen receptor modulator (SERM); fulvestrant, a selective estrogen receptor degrader (SERD); and aromatase inhibitors (AIs), which block estrogen synthesis. However, intrinsic or acquired hormone resistance eventually develops, leading to disease progression. The combination of ET with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) has been shown to significantly increase progression-free survival (PFS) and, in some cases, overall survival (OS). CDK4/6is works by arresting the cell cycle in the G1 phase, preventing DNA synthesis, and enhancing the efficacy of ET. This review highlights the key mechanisms of resistance to ET, whether used alone or in combination with biological agents, as well as emerging therapeutic strategies aimed at overcoming resistance. Addressing ET resistance remains a work in progress, and in the near future, better patient selection for different therapeutic approaches is expected through the identification of more precise biological and genetic markers. In particular, liquid biopsy may provide a real-time portrait of the disease, offering insights into mechanisms driving ET resistance and cancer progression. Full article

(This article belongs to the Special Issue Molecular Research and Cellular Biology of Breast Cancer)

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13 pages, 2137 KiB

Open AccessArticle

Genome-Wide Association Study and Candidate Gene Mining of Husk Number Trait in Maize

by Yancui Wang, Shukai Wang, Dusheng Lu, Ming Chen, Baokun Li, Zhenhong Li, Haixiao Su, Jing Sun, Pingping Xu and Cuixia Chen

Int. J. Mol. Sci. 2025, 26(7), 3437; https://doi.org/10.3390/ijms26073437 - 7 Apr 2025

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Abstract

Husk number (HN) trait is an important factor affecting maize kernel dehydration rate after the physiological maturity stage. In general, a reasonable reduction in HN is a key target sought for breeding maize varieties that are suitable for mechanized harvesting. In this study, [...] Read more.

Husk number (HN) trait is an important factor affecting maize kernel dehydration rate after the physiological maturity stage. In general, a reasonable reduction in HN is a key target sought for breeding maize varieties that are suitable for mechanized harvesting. In this study, the HN of a maize natural population panel containing 232 inbred lines was analyzed, and the results showed a broad-sense heritability of 0.89, along with a wide range of phenotypic variation. With the best linear unbiased prediction (BLUP) values across the three environments, a genome-wide association study (GWAS) was conducted using 995,106 single-nucleotide polymorphism (SNP) markers. A total of 16 SNPs significantly associated with HN were identified by the mixed linear model and general linear model using the TASSEL 5.0 software program. A local linkage disequilibrium (LD) study was performed to infer the candidate interval around the lead SNPs. A total of 19 functionally annotated genes were identified. The candidate genes were divided into multiple functional types, including transcriptional regulation, signal transduction, and metabolic and cellular transport. These results provide hints for the understanding of the genetic basis of the HN trait and for the breeding of maize varieties with fewer HN and faster dehydration rate. Full article

(This article belongs to the Special Issue Research on Plant Genomics and Breeding: 2nd Edition)

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13 pages, 2008 KiB

Open AccessArticle

Dppa2 Promotes Early Embryo Development Through Regulating PDH Expression Pattern During Zygotic Genome Activation

by Anqi Di, Xinyi Zhang, Lishuang Song, Song Wang, Xuefei Liu, Chunling Bai, Guanghua Su, Guangpeng Li and Lei Yang

Int. J. Mol. Sci. 2025, 26(7), 3436; https://doi.org/10.3390/ijms26073436 - 6 Apr 2025

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Abstract

During embryonic development, zygotic genome activation (ZGA) is a critical event that determines the rational process and the fate of embryonic cells. The tricarboxylic acid cycle (TCA cycle) provides necessary reactants and energy for biological activities such as genome activation, chromatin opening, and [...] Read more.

During embryonic development, zygotic genome activation (ZGA) is a critical event that determines the rational process and the fate of embryonic cells. The tricarboxylic acid cycle (TCA cycle) provides necessary reactants and energy for biological activities such as genome activation, chromatin opening, and epigenetic modifications during ZGA. Recent studies have shown that during ZGA, core enzymes associated with TCA briefly enter the nucleus and participate in initiating the ZGA process. However, the regulatory relationship between ZGA factors, such as Dux, Dppa2, and Dppa4, and the core enzymes of the TCA cycle remains unknown. In this study, we found that Dppa2 plays a key role in ZGA by directly determining the localization of TCA core enzymes, thereby affecting the early embryonic development. To further investigate the effect of Dppa2 on the localization of pyruvate dehydrogenase (PDH), we followed the establishment of an inducible Dppa2 transgenic mouse model. We found that the “chronoectopic” expression of Dppa2 prior to normal ZGA time could lead to the advanced nuclear localization of PDH. In summary, Dppa2 plays a key role in ZGA, directly determining the location of TCA core enzymes in early embryos. This study provides a theoretical basis for early embryonic development at the metabolic regulation level. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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7 pages, 428 KiB

Open AccessCommentary

Sidransky Syndrome—GBA1-Related Parkinson’s Disease and Its Targeted Therapies

by Majdolen Istaiti, Gilad Yahalom, Mikhal Cohen, Volha Skrahina, Aliaksandr Skrahin, Jan Lukas, Arndt Rolfs and Ari Zimran

Int. J. Mol. Sci. 2025, 26(7), 3435; https://doi.org/10.3390/ijms26073435 - 6 Apr 2025

Viewed by 287

Abstract

Sidransky syndrome represents a distinct variant of Parkinson’s disease (PD) that is linked to pathogenic variants in the glucocerebrosidase (GBA1) gene. This disorder exhibits an earlier onset, a more severe course, and a higher dementia prevalence compared to idiopathic PD. While [...] Read more.

Sidransky syndrome represents a distinct variant of Parkinson’s disease (PD) that is linked to pathogenic variants in the glucocerebrosidase (GBA1) gene. This disorder exhibits an earlier onset, a more severe course, and a higher dementia prevalence compared to idiopathic PD. While the pathogenesis remains debated between loss-of-function and gain-of-function mechanisms, targeted therapies are emerging. Pharmacological chaperones (PCs), like high-dose Ambroxol, aim to mitigate enzyme misfolding—a primary driver of this disorder—rather than addressing metabolic deficiencies seen in Gaucher disease. Despite failed trials of substrate reduction therapies, current clinical trials with Ambroxol and other PCs highlight promising avenues for disease modification. This commentary advocates for increased awareness of Sidransky syndrome to advance diagnostic strategies, promote genetic testing, and refine targeted treatments, with the potential to transform care for GBA1-related PD and prodromal stages of the disease. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Genetic Variants of Parkinson’s Disease)

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18 pages, 36758 KiB

Open AccessArticle

Prion-Dependent Lethality of sup35 Missense Mutations Is Caused by Low GTPase Activity of the Mutant eRF3 Protein

by Nina P. Trubitsina, Olga M. Zemlyanko, Andrew G. Matveenko, Stanislav A. Bondarev, Svetlana E. Moskalenko, Evgeniia M. Maksiutenko, Anna A. Zudilova, Tatiana M. Rogoza and Galina A. Zhouravleva

Int. J. Mol. Sci. 2025, 26(7), 3434; https://doi.org/10.3390/ijms26073434 - 6 Apr 2025

Viewed by 285

Abstract

The essential SUP35 gene encodes yeast translation termination factor Sup35/eRF3. The N-terminal domain of Sup35 is also responsible for Sup35 prionization that leads to generation of the [PSI⁺] prion. Previously we isolated different types of sup35 mutations (missense and nonsense) [...] Read more.

The essential SUP35 gene encodes yeast translation termination factor Sup35/eRF3. The N-terminal domain of Sup35 is also responsible for Sup35 prionization that leads to generation of the [PSI⁺] prion. Previously we isolated different types of sup35 mutations (missense and nonsense) and demonstrated that sup35 nonsense mutations (sup35-n) are incompatible with the [PSI⁺] prion, leading to lethality of sup35-n [PSI⁺] haploid cells. Here, we show that sup35 missense mutations (sup35-m) within conservative regions of the Sup35 C-domain result in lethality of [PSI⁺] cells because of weak activity of Sup35/eRF3 as a translation termination factor. Mutant Sup35 maintain their ability to be incorporated into pre-existing [PSI⁺] aggregates and to form amyloid aggregates in vitro, while sup35-m mutations do not influence the [PSI⁺] prion induction and stability. All these mutations (D363N, R372K, T378I) are located in the conservative GTPase region of Sup35, decreasing the GTPase activity of mutated proteins. We propose that such low activity of mutant Sup35 combined with aggregation of Sup35 constituting the [PSI⁺] prion is not sufficient to maintain the viability of yeast cells. Full article

(This article belongs to the Special Issue Yeast: Molecular and Cell Biology)

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24 pages, 1598 KiB

Open AccessReview

Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review

by Enrico Celestino Nista, Simone Parello, Mattia Brigida, Giulio Amadei, Angela Saviano, Sara Sofia De Lucia, Carmine Petruzziello, Alessio Migneco and Veronica Ojetti

Int. J. Mol. Sci. 2025, 26(7), 3433; https://doi.org/10.3390/ijms26073433 - 6 Apr 2025

Viewed by 493

Abstract

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP [...] Read more.

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation. Full article

(This article belongs to the Special Issue New Molecular Mechanisms and Markers in Inflammatory Disorders, 3rd Edition)

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16 pages, 2895 KiB

Open AccessArticle

Unveiling the Forensic Potential of Oral and Nasal Microbiota in Post-Mortem Interval Estimation

by Ji Chen, Qi Wei, Fan Yang, Yanan Liu, Yurong Zhao, Han Zhang, Xin Huang, Jianye Zeng, Xiang Wang and Suhua Zhang

Int. J. Mol. Sci. 2025, 26(7), 3432; https://doi.org/10.3390/ijms26073432 - 6 Apr 2025

Viewed by 299

Abstract

Microbiota have emerged as a promising tool for estimating the post-mortem interval (PMI) in forensic investigations. The role of oral and nasal microbiota in cadaver decomposition is crucial; however, their distribution across human cadavers at different PMIs remains underexplored. In this study, we [...] Read more.

Microbiota have emerged as a promising tool for estimating the post-mortem interval (PMI) in forensic investigations. The role of oral and nasal microbiota in cadaver decomposition is crucial; however, their distribution across human cadavers at different PMIs remains underexplored. In this study, we collected 88 swab samples from the oral and nasal cavities of 10 healthy volunteers and 34 human cadavers. Using 16S rRNA gene sequencing, we conducted comprehensive analyses of the alpha diversity, beta diversity, and relative abundance distribution to characterize the microbial communities in both healthy individuals and cadavers at varying PMIs and under different freezing conditions. Random forest models identified Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, and Fusobacteriota as potential PMI-associated biomarkers at the phylum level for both the oral and nasal groups, along with genus-level biomarkers specific to each group. These biomarkers exhibited nonlinear changes over increasing PMI, with turning points observed on days 5, 12, and 22. The random forest inference models demonstrated that oral biomarkers at both the genus and phylum levels achieved the lowest mean absolute error (MAE) values in the training dataset (MAE = 2.16 days) and the testing dataset (MAE = 5.14 days). Additionally, freezing had minimal impact on the overall phylum-level microbial composition, although it did affect the relative abundance of certain phyla. At the genus level, significant differences in microbial biomarkers were observed between frozen and unfrozen cadavers, with the oral group showing greater stability compared to the nasal group. These findings suggest that the influence of freezing should be considered when using genus-level microbial data to estimate PMIs. Overall, our results highlight the potential of oral and nasal microbiota as robust tools for PMI estimation and emphasize the need for further research to refine predictive models and explore the environmental factors shaping microbial dynamics. Full article

(This article belongs to the Special Issue New Perspectives on Biology in Forensic Diagnostics)

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11 pages, 234 KiB

Open AccessReview

Kidney Injury Molecule-1 as a Biomarker for Renal Cancer: Current Insights and Future Perspectives—A Narrative Review

by Dragoș Puia, Marius Ivănuță and Cătălin Pricop

Int. J. Mol. Sci. 2025, 26(7), 3431; https://doi.org/10.3390/ijms26073431 - 6 Apr 2025

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Abstract

Kidney injury molecule-1 (KIM-1) is a transmembrane protein that is significantly upregulated in renal cells following injury. It has considerable potential as a biomarker for diagnosing and monitoring renal cell carcinoma (RCC). This review examines KIM-1 expression across multiple biological sources—including tissue, blood, [...] Read more.

Kidney injury molecule-1 (KIM-1) is a transmembrane protein that is significantly upregulated in renal cells following injury. It has considerable potential as a biomarker for diagnosing and monitoring renal cell carcinoma (RCC). This review examines KIM-1 expression across multiple biological sources—including tissue, blood, and urine—and highlights its strong association with RCC risk. Clinical studies have shown that KIM-1 levels decline within weeks after nephrectomy, underscoring its utility in assessing therapeutic response. Additionally, urinary KIM-1 levels correlate with histopathological outcomes following cisplatin treatment, supporting its role as a non-invasive marker for treatment effectiveness. Despite these promising findings, several challenges remain. These include variability in assay performance and the modulatory effects of the tumour microenvironment on KIM-1 expression. Overcoming these technical limitations is crucial for integrating KIM-1 into clinical workflows. Furthermore, its potential role in guiding combination therapies—such as tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and mTOR inhibitors—could enhance therapeutic precision while minimizing toxicity. Continued research is essential to validate these applications and facilitate the routine clinical use of KIM-1 in RCC management. Full article

(This article belongs to the Section Molecular Oncology)

15 pages, 3462 KiB

Open AccessArticle

Ionic Liquid Electrolyte Technologies for High-Temperature Lithium Battery Systems

by Eleonora De Santis, Annalisa Aurora, Sara Bergamasco, Antonio Rinaldi, Rodolfo Araneo and Giovanni Battista Appetecchi

Int. J. Mol. Sci. 2025, 26(7), 3430; https://doi.org/10.3390/ijms26073430 - 6 Apr 2025

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Abstract

The advent of the lithium-ion batteries (LIBs) has transformed the energy storage field, leading to significant advances in electronics and electric vehicles, which continuously demand more and more performant devices. However, commercial LIB systems are still far from satisfying applications operating in arduous [...] Read more.

The advent of the lithium-ion batteries (LIBs) has transformed the energy storage field, leading to significant advances in electronics and electric vehicles, which continuously demand more and more performant devices. However, commercial LIB systems are still far from satisfying applications operating in arduous conditions, such as temperatures exceeding 100 °C. For instance, safety issues, materials degradation, and toxic stem development, related to volatile, flammable organic electrolytes, and thermally unstable salts (LiPF₆), limit the operative temperature of conventional lithium-ion batteries, which only occasionally can exceed 50–60 °C. To overcome this highly challenging drawback, the present study proposes advanced electrolyte technologies based on innovative, safer fluids such as ionic liquids (ILs). Among the IL families, we have selected ionic liquids based on tetrabutylphosphonium and 1-ethyl-3-methyl-imidazolium cations, coupled with per(fluoroalkylsulfonyl)imide anions, for standing out because of their remarkable thermal robustness. The thermal behaviour as well as the ion transport properties and electrochemical stability were investigated even in the presence of the lithium bis(trifluoromethylsulfonyl)imide salt. Conductivity measurements revealed very interesting ion transport properties already at 50 °C, with ion conduction values ranging from 10⁻³ and 10⁻² S cm⁻¹ levelled at 100 °C. Thermal robustness exceeding 150 °C was detected, in combination with anodic stability above 4.5 V at 100 °C. Preliminary cycling tests run on Li/LiFePO₄ cells at 100 °C revealed promising performance, i.e., more than 94% of the theoretical capacity was delivered at a current rate of 0.5C. The obtained results make these innovative electrolyte formulations very promising candidates for high-temperature LIB applications and advanced energy storage systems. Full article

(This article belongs to the Special Issue Electrochemical Research of Metal Compounds and Its Energy Storage Applications)

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21 pages, 3971 KiB

Open AccessArticle

Genome-Wide Identification of the BTB Domain-Containing Protein Gene Family in Pepper (Capsicum annuum L.)

by Qiaoling Yuan, Jin Wang, Feng Liu, Xiongze Dai, Fan Zhu, Xuexiao Zou and Cheng Xiong

Int. J. Mol. Sci. 2025, 26(7), 3429; https://doi.org/10.3390/ijms26073429 - 6 Apr 2025

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Abstract

Pepper (Capsicum annuum L.), recognized as a globally preeminent vegetable, holds substantial economic and nutritional value. The BTB (broad-complex, tramtrack, and bric-a-brac) family of proteins, characterized by a highly conserved BTB domain, also denoted as the POZ domain, are intricately involved in [...] Read more.

Pepper (Capsicum annuum L.), recognized as a globally preeminent vegetable, holds substantial economic and nutritional value. The BTB (broad-complex, tramtrack, and bric-a-brac) family of proteins, characterized by a highly conserved BTB domain, also denoted as the POZ domain, are intricately involved in a diverse array of biological processes. However, the existing corpus of research regarding pepper BTB genes remains relatively meager. In this study, a total of 72 CaBTB gene members were meticulously identified from the entire genome of pepper. Phylogenetic analysis illuminated the presence of conspicuous collinear relationships between the CaBTB genes and those of its closely affiliated species. Gene expression profiling and RT-qPCR analysis revealed that multiple CaBTB genes exhibited pronounced differential expression under diverse treatment regimens. Expression pattern analysis unveiled that CaBTB25 manifested a remarkably elevated abundance in leaves. Moreover, its promoters were replete with an abundance of light-responsive cis-elements. Our comprehensive and in-depth explorations into subcellular localization revealed that CaBTB25 was predominantly detected to localize within the nucleus and lacked transcriptional activation. This research provides a crucial theoretical edifice, enabling a more profound understanding of the biological functions of the BTB gene family in pepper, thereby underscoring its potential significance within the intricate network of gene–environment interactions. Full article

(This article belongs to the Special Issue Plant Responses to Abiotic and Biotic Stresses)

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23 pages, 5646 KiB

Open AccessArticle

Therapeutic Potential of Cannabidiol Cyclodextrin Complex in Polymeric Micelle and Tetrahydrocurcumin Cyclodextrin Complex Loaded in Hydrogel to Treat Lymphedema

by Waritorn Srakhao, Titpawan Nakpheng, Mohd Cairul Iqbal Mohd Amin and Teerapol Srichana

Int. J. Mol. Sci. 2025, 26(7), 3428; https://doi.org/10.3390/ijms26073428 - 6 Apr 2025

Viewed by 501

Abstract

Cannabidiol (CBD) and tetrahydrocurcumin (THC) have demonstrated anti-inflammatory activity as well as generating new lymph vessels. We present the formulations and evaluations of CBD and THC loaded in hydrogels for the treatment of lymphedema to promote angiogenesis of lymph vessels and an anti-inflammatory [...] Read more.

Cannabidiol (CBD) and tetrahydrocurcumin (THC) have demonstrated anti-inflammatory activity as well as generating new lymph vessels. We present the formulations and evaluations of CBD and THC loaded in hydrogels for the treatment of lymphedema to promote angiogenesis of lymph vessels and an anti-inflammatory response. Six CBD-THC hydrogel formulations were prepared and evaluated. The hydrodynamic particle sizes were 302.0–545.1 nm and the zeta potentials were from −58.80 to −33.63 mV. The hydrogel pHs were 6.43–6.54. The hydrogel formulations were non-toxic for both CBD (<25 µg/mL) and THC (<12.5 µg/mL). It was observed that high-molecular-weight hyaluronic acid in hydrogel affected collagen production. Hydrogel formulations at 2 µg/mL of CBD and 1 µg/mL of THC induced human dermal lymphatic endothelial cell tube formation. CBD-THC hydrogel formulations showed a notable ability to induce angiogenesis, which suggested its potential effectiveness in promoting new lymphatic vessel formation. Moreover, CBD-THC hydrogels showed anti-inflammatory properties. Further research is needed to ensure these treatments effectively enhance lymphatic repair. Full article

(This article belongs to the Special Issue Molecular Advances on Cannabinoid and Endocannabinoid Research 2.0)

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28 pages, 12104 KiB

Open AccessArticle

The Ancestral KEAP1-NRF Pathway in Amphioxus Branchiostoma japonicum: Implications for the Evolution of Antioxidant Defense System

by Weichen Li, Xiaoqian Liang, Keyu Xiang, Hongyan Li and Yu Zhang

Int. J. Mol. Sci. 2025, 26(7), 3427; https://doi.org/10.3390/ijms26073427 - 6 Apr 2025

Viewed by 319

Abstract

The Kelch-like ECH-associated protein 1 (KEAP1)/Nuclear factor E2-related factor 2 (NRF2) pathway is a key mechanism that responds to oxidative stress and xenobiotic stimuli in vertebrates. However, knowledge of its evolutionary origins remains limited. In this study, we identify the ancestral homologues of [...] Read more.

The Kelch-like ECH-associated protein 1 (KEAP1)/Nuclear factor E2-related factor 2 (NRF2) pathway is a key mechanism that responds to oxidative stress and xenobiotic stimuli in vertebrates. However, knowledge of its evolutionary origins remains limited. In this study, we identify the ancestral homologues of KEAP1 and NRF (BjKEAP1 and BjNRF) in cephalochordate amphioxus (Branchiostoma japonicum). BjNRF uniquely combines the feature domains of vertebrates NRF1 and NRF2, marking it as an evolutionary intermediate. High expression levels of Bjkeap1 and Bjnrf in the gill, hepatic cecum, and intestine highlight their roles in environmental defense at key interface tissues. Functional studies reveal that BjKEAP1 regulates the cytoplasmic localization of BjNRF. Typical NRF2 activator sulforaphane (SFN) induces its nuclear translocation and significantly elevates the transcriptional expression of BjNRF and phase II detoxification enzymes. Moreover, exposure to the environmental toxin Benzo[a]pyrene (BaP) activates this stress response system. These findings bridge critical gaps in our understanding of this pathway in basal chordates and offer new insights into the evolutionary trajectory of the KEAP1-NRF system. Furthermore, this study highlights crucial implications for the conservation of amphioxus in deteriorating marine environments. Full article

(This article belongs to the Special Issue Gene Regulation in Endocrine Disease)

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7 pages, 185 KiB

Open AccessEditorial

Cellular and Molecular Regulatory Signals in Root Growth and Development

by Guzel Kudoyarova

Int. J. Mol. Sci. 2025, 26(7), 3426; https://doi.org/10.3390/ijms26073426 - 6 Apr 2025

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Abstract

The responses of root growth and development to environmental changes ensure that plants adequately adapt to the availability of water and nutrients [...] Full article

(This article belongs to the Special Issue Cellular and Molecular Regulatory Signals in Root Growth and Development)

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Int. J. Mol. Sci., Volume 26, Issue 7 (April-1 2025) – 628 articles

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