International Journal of Molecular Sciences

18 pages, 3360 KiB

Open AccessArticle

Positive Effect of Elevated Thawing Rate for Cryopreservation of Human Ovarian Tissue: Transcriptomic Analysis of Fresh and Cryopreserved Cells

by Qingduo Kong, Plamen Todorov, Cheng Pei, Evgenia Isachenko, Gohar Rahimi, Nina Mallmann-Gottschalk and Volodimir Isachenko

Int. J. Mol. Sci. 2024, 25(24), 13747; https://doi.org/10.3390/ijms252413747 - 23 Dec 2024

Viewed by 699

Abstract

Ovarian tissue cryopreservation has been gradually applied. It is essential to elucidate the differences between cryopreserved and fresh ovarian tissue and to refine cryopreservation protocols for improved outcomes. To explore the transcriptomic differences between fresh ovarian tissue and tissue cryopreserved with an elevated [...] Read more.

Ovarian tissue cryopreservation has been gradually applied. It is essential to elucidate the differences between cryopreserved and fresh ovarian tissue and to refine cryopreservation protocols for improved outcomes. To explore the transcriptomic differences between fresh ovarian tissue and tissue cryopreserved with an elevated thawing rate. Ovarian tissue samples were collected and cryopreserved (frozen and thawed) following RNA sequencing and histological evaluation. Three groups were formed: fresh tissue (Group 1), frozen tissue after quick thawing at 100 °C (Group 2), and frozen tissue after slow thawing at 37 °C (Group 3). KEGG analysis showed that in comparison with Group 1, DEGs in Group 2 were mainly enriched in the cortisol synthesis and ovarian steroidogenesis pathways, and DEGs in the cells of Group 3 were mainly enriched in the ovarian steroidogenesis pathway. GO analysis showed that compared to cells of Group 2, DEGs in Group 3 were primarily enriched in the SRP-dependent co-translational protein targeting pathway and co-translational protein targeting to the membrane. The results were formulated with a minimal difference in the histological evaluation of cells after quick and slow thawed tissue. Cryopreservation of ovarian tissue by the described method does not decrease follicle production but downregulates the ovarian steroidogenesis pathway, reducing estrogen and progesterone secretion. The quick thawing of ovarian tissue increases the proliferation and apoptosis pathways of cells. Full article

(This article belongs to the Special Issue Understanding Reproductive Health and Infertility: Molecular and Genetic Insights)

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24 pages, 9932 KiB

Open AccessArticle

SCOBY Cellulose-Based Materials Hydrophobized Using Stearic Acid and Apple Powder

by Malgorzata Anita Bryszewska, Daniel Gutierez Pareja, Lukasz Kaczmarek, Anna Sobczyk-Guzenda, Malgorzata Piotrowska and Damian Batory

Int. J. Mol. Sci. 2024, 25(24), 13746; https://doi.org/10.3390/ijms252413746 - 23 Dec 2024

Viewed by 534

Abstract

Bacterial cellulose (BC) is a subject of interest for researchers due to its advantageous characteristics, including a straightforward manufacturing process, biocompatibility, and extensive modification potential. The hydrophilic nature of the material is beneficial in some applications, yet a limiting factor in others. This [...] Read more.

Bacterial cellulose (BC) is a subject of interest for researchers due to its advantageous characteristics, including a straightforward manufacturing process, biocompatibility, and extensive modification potential. The hydrophilic nature of the material is beneficial in some applications, yet a limiting factor in others. This study aimed to develop BC-based materials with goFogureod moisture resistance. The modification of bacterial cellulose (BC) using apple powder, stearic acid, or a combination of these modifiers resulted in the formation of a range of materials, some of which had their surfaces additionally functionalised by coating with a mixture of apple powder and stearic acid (HSt). The nature and type of changes were confirmed by FTIR and theoretical analysis, which was conducted by modelling the interaction between cellulose and homogalacturonan or rhamnogalacturonan using SCIGRESS v.FJ 2.7 software. Changes in hydrogen bonding resulting in a weakening of the interactions between cellulose and water in the presence of pectin were demonstrated by both empirical data and modelling. The effectiveness of BC functionalisation was confirmed by material wettability. The water contact angle changed from 38° for the unmodified material to 125° for the material obtained by modification of the bacterial cellulose with glycerol followed by modification with a mixture of HSt at a concentration of 10% and AP at a concentration of 60%. The modifications produced a material with a robust hydrophobic surface. The results suggest that the surface roughness may not be the primary factor influencing the hydrophilicity or hydrophobicity of these materials but that it is more likely to be related to the interactions of components. None of the tested materials demonstrated antimicrobial activity against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger, or Candida albicans. Full article

(This article belongs to the Special Issue Recent Advances in Biopolymer Composites)

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15 pages, 6729 KiB

Open AccessArticle

Mesenchymal Stem Cell Extract Promotes Skin Wound Healing

by Zi Deng, Kengo Iwasaki, Yihao Peng and Yoshitomo Honda

Int. J. Mol. Sci. 2024, 25(24), 13745; https://doi.org/10.3390/ijms252413745 - 23 Dec 2024

Viewed by 463

Abstract

Recently, it has been reported that mesenchymal stem cell (MSC)-derived humoral factors promote skin wound healing. As these humoral factors are transiently stored in cytoplasm, we collected them as part of the cell extracts from MSCs (MSC-ext). This study aimed to investigate the [...] Read more.

Recently, it has been reported that mesenchymal stem cell (MSC)-derived humoral factors promote skin wound healing. As these humoral factors are transiently stored in cytoplasm, we collected them as part of the cell extracts from MSCs (MSC-ext). This study aimed to investigate the effects of MSC-ext on skin wound healing. We examined the effects of MSC-ext on cell proliferation and migration. Additionally, the effect of MSC-ext on skin wound healing was evaluated using a mouse skin defect model. The MSC-ext enhanced the proliferation of dermal fibroblasts, epithelial cells, and endothelial cells. It also increased the number of migrating fibroblasts and epithelial cells. The skin defects treated with MSC-ext demonstrated rapid wound closure compared to those treated with phosphate-buffered saline. The MSC-ext group exhibited a thicker dermis, larger Picrosirius red-positive areas, and a higher number of Ki67-positive cells. Our results indicate that MSC-ext promotes the proliferation and/or migration of fibroblasts, epithelial cells, and endothelial cells, and enhances skin wound healing. This suggests the therapeutic potential of MSC-ext in treating skin defects as a novel cell-free treatment modality. Full article

(This article belongs to the Special Issue Natural Product-Based Strategy for Skin Inflammatory Disorders and Regeneration)

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17 pages, 298 KiB

Open AccessArticle

Could Selected Adipokines/Cytokines Serve as Markers of Adipose Tissue Dysfunction?

by Lucyna Ostrowska, Joanna Smarkusz-Zarzecka, Beata Zyśk, Karolina Orywal, Barbara Mroczko and Urszula Cwalina

Int. J. Mol. Sci. 2024, 25(24), 13744; https://doi.org/10.3390/ijms252413744 - 23 Dec 2024

Viewed by 462

Abstract

Elevated levels of pro-inflammatory adipokines and cytokines increase the risk of developing metabolic disorders and diseases. The aim of this study was to conduct a comparative analysis of selected adipokines/cytokines in the blood serum of adults with obesity and normal body weight. The [...] Read more.

Elevated levels of pro-inflammatory adipokines and cytokines increase the risk of developing metabolic disorders and diseases. The aim of this study was to conduct a comparative analysis of selected adipokines/cytokines in the blood serum of adults with obesity and normal body weight. The study also evaluated the correlation of these adipokines/cytokines with selected biochemical blood parameters. The study included 46 individuals with first- and second-degree obesity and 35 individuals with normal body weight. The participants underwent nutritional status assessments, biochemical tests, and evaluations of adipokine and cytokine concentrations in blood serum. The study found higher median CRP concentrations in women with obesity than in those with normal weight. This increase was statistically significant. The results also showed significantly higher IL-6 levels in the obesity group compared to the control group in both women and men. Resistin and MMP-2 were significantly different between women with obesity and women with normal body weight. Multiple regression results indicated that higher total fat content was significantly associated with higher serum CRP and IL-6 levels and lower adiponectin levels. Interleukin 6 was the strongest predictor of adipose tissue dysfunction in both women and men. Potential markers in women could also include resistin and MMP-2. The findings suggest that gender significantly influences the regulation of inflammatory factors. Full article

(This article belongs to the Special Issue Cytokines in Inflammatory Signaling: 2nd Edition)

8 pages, 243 KiB

Open AccessEditorial

Animal Models of Human Disease 2.0

by Sigrun Lange and Jameel M. Inal

Int. J. Mol. Sci. 2024, 25(24), 13743; https://doi.org/10.3390/ijms252413743 - 23 Dec 2024

Viewed by 549

Abstract

The use of animal models is crucial for advancing translational research by identifying effective treatment targets and strategies for clinical application in human disease [...] Full article

(This article belongs to the Topic Animal Models of Human Disease 2.0)

11 pages, 1248 KiB

Open AccessBrief Report

Optimizing Yeast Homologous Recombination for Splicing Large Coronavirus Genome Fragments

by Guoqing Xiong, Xuan Huang, Ao Hu, Zhixin Meng, Jiazhen Cui, Yuzhong Feng, Zhili Chen, Yuanyuan Lu, Qi Yang and Gang Liu

Int. J. Mol. Sci. 2024, 25(24), 13742; https://doi.org/10.3390/ijms252413742 - 23 Dec 2024

Viewed by 579

Abstract

Reverse genetics is a useful tool for studying viruses and developing vaccines for coronaviruses. However, constructing and manipulating the coronavirus genome in Escherichia coli can be time-consuming and challenging due to its large size and instability. Homologous recombination, a genetic manipulation mechanism found [...] Read more.

Reverse genetics is a useful tool for studying viruses and developing vaccines for coronaviruses. However, constructing and manipulating the coronavirus genome in Escherichia coli can be time-consuming and challenging due to its large size and instability. Homologous recombination, a genetic manipulation mechanism found in organisms, is essential for DNA repair, gene recombination, and genetic engineering. In yeast, particularly Saccharomyces cerevisiae, homologous recombination technology is commonly used for constructing gene expression plasmids and genome editing. In this study, we successfully split and spliced a 30 kb viral genome fragment using yeast homologous recombination. By optimizing the program parameters, such as homologous arm lengths and fragment-to-vector ratios, we achieved a splicing efficiency of up to 97.9%. The optimal parameters selected were a 60 bp homologous sequence size and a vector fragment ratio of 1:2:2:2:2:2 for yeast homologous recombination of large DNA fragments. Full article

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

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23 pages, 8034 KiB

Open AccessArticle

Inflammaging Markers in the Extremely Cold Climate: A Case Study of Yakutian Population

by Alena Kalyakulina, Igor Yusipov, Elena Kondakova, Tatiana Sivtseva, Raisa Zakharova, Sergey Semenov, Tatiana Klimova, Elena Ammosova, Arseniy Trukhanov, Claudio Franceschi and Mikhail Ivanchenko

Int. J. Mol. Sci. 2024, 25(24), 13741; https://doi.org/10.3390/ijms252413741 - 23 Dec 2024

Viewed by 533

Abstract

Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near −40 °C and the minimum below −60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to [...] Read more.

Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near −40 °C and the minimum below −60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to their Central Russian counterparts, residing in a considerably milder climate. In this paper, we analyzed these cohorts from the inflammaging perspective and addressed two hypotheses: a mismatch in the immunological profiles and accelerated inflammatory aging in Yakuts. We found that the levels of 17 cytokines displayed statistically significant differences in the mean values between the groups (with minimal p-value = 2.06 × 10⁻¹⁹), and 6 of them are among 10 SImAge markers. We demonstrated that five out of these six markers (PDGFB, CD40LG, VEGFA, PDGFA, and CXCL10) had higher mean levels in the Yakutian cohort, and therefore, due to their positive chronological age correlation, might indicate a trend toward accelerated inflammatory aging. At the same time, a statistically significant biological age acceleration difference between the two cohorts according to the inflammatory SImAge clock was not detected because they had similar levels of CXCL9, CCL22, and IL6, the top contributing biomarkers to SImAge. We introduced an explainable deep neural network to separate individual inflammatory profiles between the two groups, resulting in over 95% accuracy. The obtained results allow for hypothesizing the specificity of cytokine and chemokine profiles among people living in extremely cold climates, possibly reflecting the effects of long-term human (dis)adaptation to cold conditions related to inflammaging and the risk of developing a number of pathologies. Full article

(This article belongs to the Section Molecular Immunology)

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18 pages, 4207 KiB

Open AccessReview

The Therapeutic Potential of Physical Exercise in Cancer: The Role of Chemokines

by Glenda B. B. Buzaglo, Guilherme D. Telles, Rafaela B. Araújo, Gilmar D. S. Junior, Olivia M. Ruberti, Marina L. V. Ferreira, Sophie F. M. Derchain, Felipe C. Vechin and Miguel S. Conceição

Int. J. Mol. Sci. 2024, 25(24), 13740; https://doi.org/10.3390/ijms252413740 - 23 Dec 2024

Viewed by 615

Abstract

The global increase in cancer cases and mortality has been associated with inflammatory processes, in which chemokines play crucial roles. These molecules, a subfamily of cytokines, are essential for the migration, adhesion, interaction, and positioning of immune cells throughout the body. Chemokines primarily [...] Read more.

The global increase in cancer cases and mortality has been associated with inflammatory processes, in which chemokines play crucial roles. These molecules, a subfamily of cytokines, are essential for the migration, adhesion, interaction, and positioning of immune cells throughout the body. Chemokines primarily originate in response to pathogenic stimuli and inflammatory cytokines. They are expressed by lymphocytes in the bloodstream and are divided into four classes (CC, CXC, XC, and CX3C), playing multifaceted roles in the tumor environment (TME). In the TME, chemokines regulate immune behavior by recruiting cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), which promote tumor survival. Additionally, they directly influence tumor behavior, promoting pathological angiogenesis, invasion, and metastasis. On the other hand, chemokines can also induce antitumor responses by mobilizing CD8+ T cells and natural killer (NK) cells to the tumor, reducing pro-inflammatory chemokines and enhancing essential antitumor responses. Given the complex interaction between chemokines, the immune system, angiogenic factors, and metastasis, it becomes evident how important it is to target these pathways in therapeutic interventions to counteract cancer progression. In this context, physical exercise emerges as a promising strategy due to its role modulating the expression of anti-inflammatory chemokines and enhancing the antitumor response. Aerobic and resistance exercises have been associated with a beneficial inflammatory profile in cancer, increased infiltration of CD8+ T cells in the TME, and improvement of intratumoral vasculature. This creates an environment less favorable to tumor growth and supports the circulation of antitumor immune cells and chemokines. Therefore, understanding the impact of exercise on the expression of chemokines can provide valuable insights for therapeutic interventions in cancer treatment and prevention. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Brazil, 3rd Edition)

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20 pages, 2123 KiB

Open AccessArticle

Metabolic Biomarkers of Liver Failure in Cell Models and Patient Sera: Toward Liver Damage Evaluation In Vitro

by Simone Rentschler, Sandra Doss, Lars Kaiser, Helga Weinschrott, Matthias Kohl, Hans-Peter Deigner and Martin Sauer

Int. J. Mol. Sci. 2024, 25(24), 13739; https://doi.org/10.3390/ijms252413739 - 23 Dec 2024

Viewed by 551

Abstract

Recent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The [...] Read more.

Recent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The aim of the presented study was to identify translational biomarkers for acute liver injury in human patients that can serve as biomarkers for hepatocellular injury in vivo and in vitro in simple cell models. Therefore, 188 different metabolites from patients with acute-on-chronic liver failure before and after liver transplantation were analyzed with mass spectrometry. The identified potential metabolic biomarker set, including acylcarnitines, phosphatidylcholines and sphingomyelins, was used to screen primary and permanent hepatocyte culture models for their ability to model hepatotoxic responses caused by different drugs with known and unknown hepatotoxic potential. The results obtained suggest that simple in vitro cell models have the capability to display metabolic responses in biomarkers for liver cell damage in course of the treatment with different drugs and therefore can serve as a basis for in vitro models for metabolic analysis in drug toxicity testing. The identified metabolites should further be evaluated for their potential to serve as a metabolic biomarker set indicating hepatocellular injury in vitro as well as in vivo. Full article

(This article belongs to the Special Issue Mechanism Research and Disease Assessment of Drug-Induced Liver Injury)

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20 pages, 7853 KiB

Open AccessArticle

RTL4, a Retrovirus-Derived Gene Implicated in Autism Spectrum Disorder, Is a Microglial Gene That Responds to Noradrenaline in the Postnatal Brain

by Fumitoshi Ishino, Johbu Itoh, Ayumi Matsuzawa, Masahito Irie, Toru Suzuki, Yuichi Hiraoka, Masanobu Yoshikawa and Tomoko Kaneko-Ishino

Int. J. Mol. Sci. 2024, 25(24), 13738; https://doi.org/10.3390/ijms252413738 - 23 Dec 2024

Viewed by 631

Abstract

Retrotransposon Gag-like 4 (RTL4), a gene acquired from a retrovirus, is a causative gene in autism spectrum disorder. Its knockout mice exhibit increased impulsivity, impaired short-term spatial memory, failure to adapt to novel environments, and delayed noradrenaline (NA) recovery in the [...] Read more.

Retrotransposon Gag-like 4 (RTL4), a gene acquired from a retrovirus, is a causative gene in autism spectrum disorder. Its knockout mice exhibit increased impulsivity, impaired short-term spatial memory, failure to adapt to novel environments, and delayed noradrenaline (NA) recovery in the frontal cortex. However, due to its very low expression in the brain, it remains unknown which brain cells express RTL4 and its dynamics in relation to NA. We addressed these issues using knock-in mice carrying endogenous Rtl4 fused to Venus, which encodes a fluorescent protein. The RTL4-Venus fusion protein was detected as a secreted protein in the midbrain, hypothalamus, hippocampus and amygdala in the postnatal brain. Its signal intensity was high during critical periods of neonatal adaptation to novel environments. It was upregulated by various stimuli, including isoproterenol administration, whereas it was decreased by anesthesia but was maintained by milnacipran administration, suggesting its highly sensitive response to stressors, possible dependence on the arousal state and involvement in the NA reuptake process. In vitro mixed glial culture experiments demonstrated that Rtl4 is a microglial gene and suggested that RTL4 secretion responds rapidly to isoproterenol. Microglial RTL4 plays an important role in the NA response and possibly in the development of the NAergic neuronal network in the brain. Full article

(This article belongs to the Special Issue Molecular Research on Human Retrovirus Infection: 2nd Edition)

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1 pages, 150 KiB

Open AccessCorrection

Correction: Dłuski et al. Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population. Int. J. Mol. Sci. 2024, 25, 7040

by Dominik Franciszek Dłuski, Marek Cieśla and Dorota Darmochwał-Kolarz

Int. J. Mol. Sci. 2024, 25(24), 13737; https://doi.org/10.3390/ijms252413737 - 23 Dec 2024

Viewed by 285

Abstract

In the original publication [...] Full article

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

17 pages, 7886 KiB

Open AccessArticle

A Potent Antibacterial Peptide (P6) from the De Novo Transcriptome of the Microalga Aureococcus anophagefferens

by Kexin Zhang, Xiaoting Yin, Yu Huang, Chao Liu, Qingchun Zhang, Qing Liu, Senyu Wang, Wenwu Fei, Qiong Shi and Limei Qiu

Int. J. Mol. Sci. 2024, 25(24), 13736; https://doi.org/10.3390/ijms252413736 - 23 Dec 2024

Viewed by 587

Abstract

Marine microalgae are a rich source of natural products, and their amino acid-based antimicrobial agents are usually obtained by enzymatic hydrolysis, which is inefficient and limits the research on antimicrobial peptides (AMPs) from microalgae. In this study, Aureococcus anophagefferens is used as a [...] Read more.

Marine microalgae are a rich source of natural products, and their amino acid-based antimicrobial agents are usually obtained by enzymatic hydrolysis, which is inefficient and limits the research on antimicrobial peptides (AMPs) from microalgae. In this study, Aureococcus anophagefferens is used as a model to predict antimicrobial peptides through high-throughput methods, and 471 putative peptides are identified based on the de novo transcriptome technique. Among them, three short peptides, P1, P6, and P7 were found to have antimicrobial activity against Escherichia coli, Staphylococcus aureus, Micro1coccus luteus, and yeast Pichia pastoris, and they showed no hemolytic activity even at higher concentrations up to 10 mg/mL. Especially P6, a 12-amino acid peptide with three positive charges, which exhibited the most significant microbicidal effect with the lowest MIC of 31.25 μg/mL against E. coli, and electron microscope observations showed the surface of P6 treated E. coli with granular protrusions and ruptures, suggesting that it likely caused cell death by directly destroying the bacterial cell membrane. This study may enrich the database of microalgal AMPs and demonstrate an efficient process for searching and validating microalgal source AMPs by combining computer analysis with bioactivity experiments. Full article

(This article belongs to the Special Issue Advances in Research on Antifungal Resistance)

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19 pages, 5387 KiB

Open AccessArticle

Cytotoxic Natural Products from Cryptomeria japonica (Thunb. ex L.) D.Don

by Bjørn Tobiassen Heieren, Anja Strandvoll Dyrdal, Lars Herfindal, Bjarte Holmelid, Cato Brede, Heidi Lie Andersen and Torgils Fossen

Int. J. Mol. Sci. 2024, 25(24), 13735; https://doi.org/10.3390/ijms252413735 - 23 Dec 2024

Viewed by 427

Abstract

Cryptomeria japonica is a commercially important tree native to Japan. The tree belongs to the ancient genus Cryptomeria and has found important uses as a medicinal plant, as well as a main source of timber in Japan. In recent years, there has been [...] Read more.

Cryptomeria japonica is a commercially important tree native to Japan. The tree belongs to the ancient genus Cryptomeria and has found important uses as a medicinal plant, as well as a main source of timber in Japan. In recent years, there has been an increased interest in discovering extended uses of C. japonica as a source of novel bioactive natural products with potential applications as lead compounds for active principles of future drugs. The compounds were isolated by a combination of two-phase extraction, XAD-7 Amberlite column chromatography, Sephadex LH-20 column chromatography and preparative High Performance Liquid Chromatography (HPLC). The structures were determined by a combination of several 1D and 2D Nuclear Magnetic Resonance (NMR) experiments and high-resolution mass spectrometry. Here, we report on the isolation and characterization of the novel biflavone glucoside hinokiflavone 7″-O-β-glucopyranoside, in addition to sixteen known compounds including the flavonols quercetin, quercetin 3-O-α-rhamnopyranoside and quercetin 3-O-β-galactopyranoside, the dihydroflavonols taxifolin 3-O-β-glucopyranoside, taxifolin 7-O-β-glucopyranoside, the flavanones naringenin, naringenin 7-O-β-galactopyranoside and eriodictyol 4′-O-β-glucopyranoside, the flavanol catechin, the biflavonoid amentoflavone, the dihydrochalcone phloretin 2′-O-β-glucopyranoside, the sesquiterpenoid roseoside, the polyphenolic compounds chlorogenic acid, methyl chlorogenate and the flavanocoumarins catechin-(7,8)-7″-(3,4 dihydroxyphenyl)-dihydro-8″(3H)-pyranone, and mururin A. The compounds exhibited low-to-moderate cytotoxic activity against MOLM-13 leukemia cells. Full article

(This article belongs to the Special Issue New Pharmacological Insights on Natural Macromolecules and Natural Small Molecules)

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35 pages, 12488 KiB

Open AccessArticle

LncSL: A Novel Stacked Ensemble Computing Tool for Subcellular Localization of lncRNA by Amino Acid-Enhanced Features and Two-Stage Automated Selection Strategy

by Lun Zhu, Hong Chen and Sen Yang

Int. J. Mol. Sci. 2024, 25(24), 13734; https://doi.org/10.3390/ijms252413734 - 23 Dec 2024

Viewed by 431

Abstract

Long non-coding RNA (lncRNA) is a non-coding RNA longer than 200 nucleotides, crucial for functions like cell cycle regulation and gene transcription. Accurate localization prediction from sequence information is vital for understanding lncRNA’s biological roles. Computational methods offer an effective alternative to traditional [...] Read more.

Long non-coding RNA (lncRNA) is a non-coding RNA longer than 200 nucleotides, crucial for functions like cell cycle regulation and gene transcription. Accurate localization prediction from sequence information is vital for understanding lncRNA’s biological roles. Computational methods offer an effective alternative to traditional experimental methods for annotating lncRNA subcellular positions. Existing machine learning-based methods are limited and often overlook regions with coding potential that affect the function of lncRNA. Therefore, we propose a new model called LncSL. For feature encoding, both lncRNA sequences and amino acid sequences from open reading frames (ORFs) are employed. And we selected the most suitable features by CatBoost and integrated them into a new feature set. Additionally, a voting process with seven feature selection algorithms identified the higher contributive features for training our final stacked model. Additionally, an automatic model selection strategy is constructed to find a better performance meta-model for assembling LncSL. This study specifically focuses on predicting the subcellular localization of lncRNA in the nucleus and cytoplasm. On two benchmark datasets called S1 and S2 datasets, LncSL outperformed existing methods by 6.3% to 12.3% in the Matthew’s correlation coefficient on a balanced test dataset. On an unbalanced independent test dataset sourced from S1, LncSL improved by 4.7% to 18.6% in the Matthew’s correlation coefficient, which further demonstrates that LncSL is superior to other compared methods. In all, this study presents an effective method for predicting lncRNA subcellular localization through enhancing sequence information, which is always overlooked by traditional methods, and addressing contributive meta-model selection problems, which can offer new insights for other bioinformatics problems. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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18 pages, 8001 KiB

Open AccessArticle

Studies on the Physiological Response of Hemerocallis middendorffii to Two Types of Drought Stresses

by Qi Wang, Xi Lu, Yue Sun, Jiahui Yu, Qingtao Cao, Yiting Xiao, Nan Jiang, Lifei Chen and Yunwei Zhou

Int. J. Mol. Sci. 2024, 25(24), 13733; https://doi.org/10.3390/ijms252413733 - 23 Dec 2024

Viewed by 373

Abstract

Drought is a major environmental factor limiting plant growth and development. Hemerocallis middendorffii is a perennial herbaceous plant with high drought resistance, and high ornamental and application values. Understanding the mechanism of drought stress resistance in H. middendorffii is helpful for better utilization [...] Read more.

Drought is a major environmental factor limiting plant growth and development. Hemerocallis middendorffii is a perennial herbaceous plant with high drought resistance, and high ornamental and application values. Understanding the mechanism of drought stress resistance in H. middendorffii is helpful for better utilization of plant resources and selection of excellent germplasms. In this study, the phenological and physiological traits of H. middendorffii were comprehensively analyzed under natural drought stress (ND) and PEG-simulated drought stress (PD), and the resistance of H. middendorffii to different levels of drought stress was evaluated. ND was treated using a natural water loss method. PD was treated under drought stress by using PEG-6000. H. middendorffii were able to grow within 15 d of ND and 4 d of 20% PD. Beyond this drought time, H. middendorffii will wilt and lose their ornamental value. Further study showed that H. middendorffii protect themselves from damage and enhance drought resistance mainly by increasing the content of osmoregulatory substances, enhancing the activity of antioxidant enzymes, and inhibiting photosynthesis. Malondialdehyde (MDA) content accumulated rapidly at 15 d of ND and 7 d of PD. Antioxidant enzyme activities peaked at 15 d of ND and 4 d of PD. Photosynthetic parameters decreased at 15 d of ND and 4 d of 20% PD, respectively. Moreover, we identified that the HmWRKY9 gene was up-regulated for expression in the leaves after ND and PD. HmWRKY9 may be involved in regulating the response of H. middendorffii to drought stress. Full article

(This article belongs to the Special Issue Physiology and Molecular Biology of Plant Stress Tolerance: 2nd Edition)

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11 pages, 2756 KiB

Open AccessArticle

Identification and Transcriptome Analysis of Bursaphelenchus xylophilus with Excellent Low Temperature Resistance

by Yue Zhang, Ruiwen Zhao, Tingting Jing, Sixi Lin and Xiaolei Ding

Int. J. Mol. Sci. 2024, 25(24), 13732; https://doi.org/10.3390/ijms252413732 - 23 Dec 2024

Viewed by 353

Abstract

Bursaphelenchus xylophilus is one of the most destructive quarantine pests, causing irreversible damage to pine trees. However, the unexpected identification of pine wilt disease in Northern China indicates that Bursaphelenchus xylophilus can survive under low temperatures. In this study, we analyzed the reproductivity [...] Read more.

Bursaphelenchus xylophilus is one of the most destructive quarantine pests, causing irreversible damage to pine trees. However, the unexpected identification of pine wilt disease in Northern China indicates that Bursaphelenchus xylophilus can survive under low temperatures. In this study, we analyzed the reproductivity variations among 18 different isolates, and SC13 was identified to have excellent low temperature resistance. Subsequent molecular analysis of SC13 indicated its distinct gene expression under low temperatures. The epidermal growth factor, nematode cuticle collagen and G-protein-coupled receptor genes with environmental adaptation functions were demonstrated to be differentially expressed under low temperatures. Meanwhile, morphological observations also indicated that SC13 contained significantly more lipid drops in low-temperature treatments. Generally, the identification of representative Bursaphelenchus xylophilus isolates will facilitate relevant studies in the future, and the discovery of the gene expression and morphological changes of Bursaphelenchus xylophilus under low temperatures could expand the current understanding of the environmental adaption abilities of such invasive nematodes. Full article

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

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10 pages, 8815 KiB

Open AccessArticle

Comparative Analysis of Symmetry Parameters in the E2 Inner Core of the Pyruvate Dehydrogenase Complex

by Han-ul Kim, Myeong Seon Jeong, Mi Young An, Yoon Ho Park, Sun Hee Park, Sang J. Chung, Yoon-sun Yi, Sangmi Jun, Young Kwan Kim and Hyun Suk Jung

Int. J. Mol. Sci. 2024, 25(24), 13731; https://doi.org/10.3390/ijms252413731 - 23 Dec 2024

Viewed by 393

Abstract

Recent advances in cryo-electron microscopy (cryo-EM) have facilitated the high-resolution structural determination of macromolecular complexes in their native states, providing valuable insights into their dynamic behaviors. However, insufficient understanding or experience with the cryo-EM image processing parameters can result in the loss of [...] Read more.

Recent advances in cryo-electron microscopy (cryo-EM) have facilitated the high-resolution structural determination of macromolecular complexes in their native states, providing valuable insights into their dynamic behaviors. However, insufficient understanding or experience with the cryo-EM image processing parameters can result in the loss of biological meaning. In this paper, we investigate the dihydrolipoyl acetyltransferase (E2) inner core complex of the pyruvate dehydrogenase complex (PDC) and reconstruct the 3D maps using five different symmetry parameters. The results demonstrate that the reconstructions yield structurally identical 3D models even at a near-atomic structure. This finding underscores a crucial message for researchers engaging in single-particle analysis (SPA) with relatively user-friendly and convenient image processing software. This approach helps reduce the risk of missing critical biological details, such as the dynamic properties of macromolecules. Full article

(This article belongs to the Special Issue Structural Dynamics of Macromolecules)

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12 pages, 1865 KiB

Open AccessArticle

A Possible Phenotype-to-Genotype Association of Novel Single-Nucleotide Variants in the Coding Exons of the ZNF469 Gene to Arterial Aneurysmal and Dissection Diseases

by Adam Wolf, Peyton Moore, Charles Hong and Mohanakrishnan Sathyamoorthy

Int. J. Mol. Sci. 2024, 25(24), 13730; https://doi.org/10.3390/ijms252413730 - 23 Dec 2024

Viewed by 386

Abstract

After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a [...] Read more.

After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a total cohort of 135 with arterial aneurysms or dissections who revealed single-nucleotide variants in ZNF469 with no other alterations in a panel of 35 genes associated with aneurysmal and dissection disorders. Five out of nine (5/9) single-nucleotide variants were in Exon 1, and four out of nine (4/9) mutations were in Exon 2, both of which are principal coding exons for this gene. Eight out of nine (8/9) were ACMG variants of unknown significance (VUSs), and one out of nine (1/9) was an ACMG pathogenic mutation previously associated to brittle cornea syndrome (BCS). Of our nine subjects, four (44.4%) experienced clinically significant vascular dissection, and four (44.4%) had a family history of one or more first-degree relatives with aneurysmal or dissection diseases. This novel genetic case series significantly strengthens our initial discovery of ZNF469’s potential association with arterial aneurysmal/dissection diseases through the study of this cohort of unrelated patients. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Zinc Finger Proteins in Biological Processes and Diseases)

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11 pages, 6590 KiB

Open AccessArticle

Genome-Wide Analysis of the Metallocarboxypeptidase Inhibitor Family Reveals That AbMCPI8 Affects Root Development and Tropane Alkaloid Production in Atropa belladonna

by Shengyu Yang, Yi Wang, Shiyu Wan, Can Zhang, Siyuan Liao, Min Chen, Xiaozhong Lan, Zhihua Liao and Lingjiang Zeng

Int. J. Mol. Sci. 2024, 25(24), 13729; https://doi.org/10.3390/ijms252413729 - 23 Dec 2024

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Abstract

Atropa belladonna is a medicinal plant and an important source for the commercial production of tropane alkaloids (TAs), such as scopolamine and hyoscyamine, which are used clinically for their anticholinergic properties. In this study, we identified 16 metallocarboxypeptidase inhibitor (MCPI) genes from A. [...] Read more.

Atropa belladonna is a medicinal plant and an important source for the commercial production of tropane alkaloids (TAs), such as scopolamine and hyoscyamine, which are used clinically for their anticholinergic properties. In this study, we identified 16 metallocarboxypeptidase inhibitor (MCPI) genes from A. belladonna (AbMCPIs), which are grouped into three subgroups based on phylogenetic relationships and are distributed across 10 chromosomes. Promoter analysis showed that most cis-regulatory elements were related to defense and stress responses, such as drought, low-temperature, ABA (abscisic acid), GA (gibberellin), auxin, light and MeJA responsiveness. A gene encoding a putative metallocarboxypeptidase inhibitor (AbMCPI8) is cloned from A. belladonna and characterized. AbMCPI8 shows similar tissue expression pattern to TA biosynthesis genes such as AbPMT, AbAT4, AbTRI, etc., with exclusive expression in the roots. When AbMCPI8 is silenced by virus-induced gene silencing (VIGS), the root growth is markedly inhibited and the production of hyoscyamine and scopolamine is significantly reduced. Our findings indicate a positive role of AbMCPI8 in root development, which could positively affect TA production in A. belladonna. Full article

(This article belongs to the Special Issue Regulation and Application of Bioactive Metabolites in Plants)

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18 pages, 8167 KiB

Open AccessArticle

Genome-Wide Analysis of the PYL Gene Family in Betula platyphylla and Its Responses to Abiotic Stresses

by Jiajie Yu, Ruiqi Wang, Xiang Zhang and Su Chen

Int. J. Mol. Sci. 2024, 25(24), 13728; https://doi.org/10.3390/ijms252413728 - 23 Dec 2024

Viewed by 436

Abstract

Abscisic acid (ABA) is a key phytohormone that participates in various plant biological processes, such as seed germination, senescence, stomatal movement, and flowering. In the ABA signal transduction pathway, Pyrabactin Resistance 1 (PYR1)/PYR1-Like (PYL)/Regulatory Component is the core module for ABA perception. In [...] Read more.

Abscisic acid (ABA) is a key phytohormone that participates in various plant biological processes, such as seed germination, senescence, stomatal movement, and flowering. In the ABA signal transduction pathway, Pyrabactin Resistance 1 (PYR1)/PYR1-Like (PYL)/Regulatory Component is the core module for ABA perception. In this study, a total of 12 PYL family members were identified in birch (Betula platyphylla Suk.) from a genome-wide range that can be divided into 3 subgroups according to their evolutionary relationships. The physiochemical properties of the 12 BpPYLs were characterized, and the members of the same subgroups share more similar exon–intron and motif patterns. The results of synteny analysis showed two syntenic gene pairs within BpPYL family members and 12, 8, 19, and 6 syntenic gene pairs between BpPYLs and AtPYLs, OsPYLs, PtPYLs, and ZmPYLs, respectively. Multiple cis-acting elements were identified in the promoters of BpPYLs, including stress response, phytohormone signaling, and growth and development. The results of GO and KEGG enrichment analysis showed that BpPYLs were enriched in the pathways mainly related to ABA signaling and cell communication. The results of RT-qPCR verified the expressional responses of BpPYLs to ABA, salt, and PEG treatments. Furthermore, the positive roles of BpPYL3 and BpPYL11 were proven by using salt-tolerant yeast transformation. This study provides a reference for research on ABA signal transduction and forest tree responses upon abiotic stresses. Full article

(This article belongs to the Special Issue Advances in Forest Tree Physiology, Breeding and Genetic Research: 2nd Edition)

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38 pages, 3166 KiB

Open AccessReview

The Impact of Calcium Overload on Cellular Processes: Exploring Calcicoptosis and Its Therapeutic Potential in Cancer

by Adrianna Gielecińska, Mateusz Kciuk and Renata Kontek

Int. J. Mol. Sci. 2024, 25(24), 13727; https://doi.org/10.3390/ijms252413727 - 23 Dec 2024

Viewed by 734

Abstract

The key role of calcium in various physiological and pathological processes includes its involvement in various forms of regulated cell death (RCD). The concept of ‘calcicoptosis’ has been introduced as a calcium-induced phenomenon associated with oxidative stress and cellular damage. However, its definition [...] Read more.

The key role of calcium in various physiological and pathological processes includes its involvement in various forms of regulated cell death (RCD). The concept of ‘calcicoptosis’ has been introduced as a calcium-induced phenomenon associated with oxidative stress and cellular damage. However, its definition remains controversial within the research community, with some considering it a general form of calcium overload stress, while others view it as a tumor-specific calcium-induced cell death. This review examines ‘calcicoptosis’ in the context of established RCD mechanisms such as apoptosis, necroptosis, ferroptosis, and others. It further analyzes the intricate relationship between calcium dysregulation and oxidative stress, emphasizing that while calcium overload often triggers cell death, it may not represent an entirely new type of RCD but rather an extension of known pathways. The purpose of this paper is to discuss the implications of this perspective for cancer therapy focusing on calcium-based nanoparticles. By investigating the connections between calcium dynamics and cell death pathways, this review contributes to the advancement of our understanding of calcicoptosis and its possible therapeutic uses. Full article

(This article belongs to the Section Molecular Biology)

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14 pages, 6770 KiB

Open AccessArticle

Genomic Analysis and Functional Validation of Bidirectional Promoters in Medaka (Oryzias latipes)

by Jingjie Liang, Yan Huang, Jiangling Li, Ruoxue Chen, Yanlong Lin, Haiqing Li, Xiangrui Cao and Tiansheng Chen

Int. J. Mol. Sci. 2024, 25(24), 13726; https://doi.org/10.3390/ijms252413726 - 23 Dec 2024

Viewed by 361

Abstract

Bidirectional promoters (BDPs) regulate the transcription of two adjacent, oppositely oriented genes, offering a compact structure with significant potential for multigene expression systems. Although BDPs are evolutionarily conserved, their regulatory roles and sequence characteristics vary across species, with limited studies in fish. Here, [...] Read more.

Bidirectional promoters (BDPs) regulate the transcription of two adjacent, oppositely oriented genes, offering a compact structure with significant potential for multigene expression systems. Although BDPs are evolutionarily conserved, their regulatory roles and sequence characteristics vary across species, with limited studies in fish. Here, we systematically analyzed the distribution, sequence features, and expression patterns of BDPs in the medaka (Oryzias latipes) genome. A total of 1737 divergent gene pairs, representing 13% of medaka genes, were identified as potentially regulated by BDPs. These genes are enriched in essential biological processes, including organelle function, RNA processing, and ribosome biogenesis. Transcriptomic analysis revealed that co-regulation (co-expression and co-silencing) is a prominent feature of these gene pairs, with variability influenced by tissue and sex. Sequence analysis showed that medaka BDPs are compact, with most fragments under 400 bp and an average GC content of 42.06%. Validation experiments confirmed the bidirectional transcriptional activity of three histone-related BDPs in both medaka SG3 cells and embryos, demonstrating effective and robust regulatory efficiency. This study enhances our understanding of the genomic organization and transcriptional regulation in fish and provides a valuable reference for developing species-specific multigene expression systems in fish genetic engineering. Full article

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

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19 pages, 11189 KiB

Open AccessArticle

Mode of Metal Ligation Governs Inhibition of Carboxypeptidase A

by Jorge Antonio Amador Balderas, Frank Beierlein, Anselm H. C. Horn, Senta Volkenandt, Leon Völcker, Nikoo Mokhtari, Jules Cesar Epee Ndongue and Petra Imhof

Int. J. Mol. Sci. 2024, 25(24), 13725; https://doi.org/10.3390/ijms252413725 - 23 Dec 2024

Viewed by 425

Abstract

Carboxypeptidase is a Zn-dependent protease that specifically recognises and hydrolyses peptides with a hydrophobic side chain at the C-terminal residue. According to hydrolysis mechanisms proposed in the literature, catalysis requires a water molecule to be close to the Zn ion so as to [...] Read more.

Carboxypeptidase is a Zn-dependent protease that specifically recognises and hydrolyses peptides with a hydrophobic side chain at the C-terminal residue. According to hydrolysis mechanisms proposed in the literature, catalysis requires a water molecule to be close to the Zn ion so as to be activated as a nucleophile. Among small molecules that resemble the slowly hydrolysed Gly-Tyr peptide, which have been previously designed as inhibitors and characterised structurally, a variant with the terminal amino acid in a D-configuration has been the most effective. Our molecular dynamics simulations of carboxypeptidase complexed with different variants of those inhibitor ligands as well as variants of the Gly-Tyr peptide show that the strength of the inhibitory effect is not related to the binding strength of the ligand. Our data rather support an earlier notion that the inhibition is, at least partially, due to blocking a coordination site at the Zn ion by the ligand coordinating the metal ion in a bidentate fashion. Full article

(This article belongs to the Special Issue Mechanism of Enzyme Catalysis: When Structure Meets Function)

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20 pages, 8670 KiB

Open AccessArticle

Cell Membrane- and Extracellular Vesicle-Coated Chitosan Methacrylate-Tripolyphosphate Nanoparticles for RNA Delivery

by Wen Jie Melvin Liew, Syed Abdullah Alkaff, Sheng Yuan Leong, Marin Zhen Lin Yee, Han Wei Hou and Bertrand Czarny

Int. J. Mol. Sci. 2024, 25(24), 13724; https://doi.org/10.3390/ijms252413724 - 23 Dec 2024

Viewed by 1149

Abstract

mRNA-based vaccines against the COVID-19 pandemic have propelled the use of nucleic acids for drug delivery. Conventional lipid-based carriers, such as liposomes and nanolipogels, effectively encapsulate and deliver RNA but are hindered by issues such as premature burst release and immunogenicity. To address [...] Read more.

mRNA-based vaccines against the COVID-19 pandemic have propelled the use of nucleic acids for drug delivery. Conventional lipid-based carriers, such as liposomes and nanolipogels, effectively encapsulate and deliver RNA but are hindered by issues such as premature burst release and immunogenicity. To address these challenges, cell membrane-coated nanoparticles offer a promising alternative. We developed a novel nanoparticle system using chitosan methacrylate-tripolyphosphate (CMATPP), which capitalizes on interactions involving membrane proteins at biointerfaces. Ionic crosslinking between chitosan methacrylate and tripolyphosphate facilitates the formation of nanoparticles amenable to coating with red blood cell (RBC) membranes, extracellular vesicles (EVs), and cell-derived nanovesicles (CDNs). Coating CMATPP nanoparticles with RBC membranes effectively mitigated the initial burst release of encapsulated small interfering RNA (siRNA), sustaining controlled release while preserving membrane proteins. This concept was extended to EVs, where CMATPP nanoparticles and CDNs were incorporated into a microfluidic device and subjected to electroporation to create hybrid CDN-CMATPP nanoparticles. Our findings demonstrate that CMATPP nanoparticles are a robust siRNA delivery system with suppressed burst release and enhanced membrane properties conferred by cell or vesicle membranes. Furthermore, the adaptation of the CDN-CMATPP nanoparticle formation in a microfluidic device suggests its potential for personalized therapies using diverse cell sources and increased throughput via automation. This study underscores the versatility and efficacy of CMATPP nanoparticles in RNA delivery, offering a pathway towards advanced therapeutic strategies that utilize biomimetic principles and microfluidic technologies. Full article

(This article belongs to the Special Issue Biomaterials for Drug Delivery and Advanced Therapies)

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10 pages, 258 KiB

Open AccessArticle

The Prevalence and the Underlying Mechanisms of Fosfomycin Resistance of Escherichia coli and Salmonella spp. Among Cattle in Japan

by Yuta Hosoi, Michiko Kawanishi, Saki Harada, Mio Kumakawa, Mari Matsuda and Hideto Sekiguchi

Int. J. Mol. Sci. 2024, 25(24), 13723; https://doi.org/10.3390/ijms252413723 - 23 Dec 2024

Viewed by 424

Abstract

To investigate fosfomycin resistance rates in cattle across Japan, we carried out susceptibility tests. To identify the genes contributing to fosfomycin resistance, we performed whole-genome sequencing on the fosfomycin-resistant strains. Escherichia coli were sampled from healthy cattle (n = 292, combined total [...] Read more.

To investigate fosfomycin resistance rates in cattle across Japan, we carried out susceptibility tests. To identify the genes contributing to fosfomycin resistance, we performed whole-genome sequencing on the fosfomycin-resistant strains. Escherichia coli were sampled from healthy cattle (n = 292, combined total from 2017, 2020, 2021, and 2022) and diseased cattle (n = 73, from 2021 to 2022). Salmonella spp. were obtained from diseased cattle (n = 74 from 2021 to 2022). These samples originated from different and non-duplicated farms. The MICs to fosfomycin were measured using an agar dilution method with a breakpoint of 256 μg/mL. We conducted whole-genome sequencing with a MiSeq, followed by in silico analysis of the acquired draft genomes. The resistance rates were 0.3% (95% CI [0–1.9%]), 6.8% (95% CI [2.3–15.3%]), and 1.4% (95% CI [0–7.3%]). The FosA3 gene was detected in five out of six fosfomycin-resistant E. coli strains and one Salmonella spp. strain. The fosfomycin-resistant Salmonella spp. strain also has a fosA7 gene. One E. coli strain showed resistance to fosfomycin without having the fosA3 gene, and with the mutations of glpT, uhpT, uhpT and ptsI, and with the existence of efflux pumps. The nationwide scale of resistance rates to fosfomycin in E. coli isolated from healthy and diseased cattle and that of Salmonella spp. from diseased cattle were revealed for the first time, and the resistance rates were low. In addition, genes linked to the mechanism of fosfomycin resistance were identified. Full article

(This article belongs to the Special Issue Current Advances and Perspectives in Microbial Genetics and Genomics)

13 pages, 2204 KiB

Open AccessReview

The Emerging Role of Schwann Cells in the Tumor Immune Microenvironment and Its Potential Clinical Application

by Shan Zhang, Jing Chen, Fanjun Cheng and Fang Zheng

Int. J. Mol. Sci. 2024, 25(24), 13722; https://doi.org/10.3390/ijms252413722 - 23 Dec 2024

Viewed by 570

Abstract

As the primary glial cells in the peripheral nervous system (PNS), Schwann cells (SCs) have been proven to influence the behavior of cancer cells profoundly and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Indeed, the [...] Read more.

As the primary glial cells in the peripheral nervous system (PNS), Schwann cells (SCs) have been proven to influence the behavior of cancer cells profoundly and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Indeed, the tumor microenvironment (TME) is a critical factor that can significantly limit the efficacy of immunotherapeutic approaches. The TME promotes tumor progression in part by reshaping an immunosuppressive state. The immunosuppressive TME is the result of the crosstalk between the tumor cells and the different immune cell subsets, including macrophages, natural killer (NK) cells, dendritic cells (DCs), lymphocytes, myeloid-derived suppressor cells (MDSCs), etc. They are closely related to the anti-tumor immune status and the clinical prognosis of cancer patients. Increasing research demonstrates that SCs influence these immune cells and reshape the formation of the immunosuppressive TME via the secretion of various cytokines, chemokines, and other effector molecules, eventually facilitating immune evasion and tumor progression. In this review, we summarize the SC reprogramming in TME, the emerging role of SCs in tumor immune microenvironment, and the underlying mechanisms involved. We also discuss the possible therapeutic strategies to selectively target SCs, providing insights and perspectives for future research and clinical studies involving SC-targeted treatment. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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15 pages, 2977 KiB

Open AccessArticle

Jeju Citrus (Citrus unshiu) Leaf Extract and Hesperidin Inhibit Small Intestinal α-Glucosidase Activities In Vitro and Postprandial Hyperglycemia in Animal Model

by Gi-Jung Kim, Yelim Jang, Kyoung-Tae Kwon, Jae-Won Kim, Seong-IL Kang, Hee-Chul Ko, Jung-Yun Lee, Emmanouil Apostolidis and Young-In Kwon

Int. J. Mol. Sci. 2024, 25(24), 13721; https://doi.org/10.3390/ijms252413721 - 23 Dec 2024

Viewed by 442

Abstract

Citrus fruits are widely distributed in East Asia, and tea made from citrus peels has demonstrated health benefits, such as a reduction in fever, inflammation, and high blood pressure. However, citrus leaves have not been evaluated extensively for their possible health benefits. In [...] Read more.

Citrus fruits are widely distributed in East Asia, and tea made from citrus peels has demonstrated health benefits, such as a reduction in fever, inflammation, and high blood pressure. However, citrus leaves have not been evaluated extensively for their possible health benefits. In this study, the α-glucosidase-inhibitory activity of Jeju citrus hot-water (CW) and ethyl alcohol (CE) extracts, along with hesperidin (HP) (a bioactive compound in citrus leaf extracts), was investigated, and furthermore, their effect on postprandial blood glucose reduction in an animal model was determined. The hesperidin contents of CW and CE were 15.80 ± 0.18 and 39.17 ± 0.07 mg/g-extract, respectively. Hesperidin inhibited α-glucosidase (IC₅₀, 4.39), sucrase (0.50), and CE (2.62) and demonstrated higher α-glucosidase inhibitory activity when compared to CW (4.99 mg/mL). When using an SD rat model, during sucrose and starch loading tests with CE (p < 0.01) and HP (p < 0.01), a significant postprandial blood glucose reduction effect was observed when compared to the control. The maximum blood glucose levels (Cmax) of the CE administration group decreased by about 15% (from 229.3 ± 14.5 to 194.0 ± 7.4, p < 0.01) and 11% (from 225.1 ± 13.8 to 201.1 ± 7.2 hr·mg/dL, p < 0.05) in the sucrose and starch loading tests, respectively. Our findings suggest that citrus leaf extracts standardized to hesperidin may reduce postprandial blood glucose levels through the observed inhibitory effect against sucrase, which results in delayed carbohydrate absorption. Our findings provide a biochemical rationale for further evaluating the benefits of citrus leaves. Full article

(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2024)

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9 pages, 273 KiB

Open AccessCommunication

Compartmentalization of the Inflammatory Response in the Pericardial Cavity in Patients Undergoing Cardiac Surgery

by Mohammad M. El-Diasty, Javier Rodríguez, Luis Pérez, Souhayla Souaf, Sonia Eiras and Angel L. Fernández

Int. J. Mol. Sci. 2024, 25(24), 13720; https://doi.org/10.3390/ijms252413720 - 23 Dec 2024

Viewed by 527

Abstract

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in [...] Read more.

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in all pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included, of which 66% were males. Serum levels of IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery. Full article

(This article belongs to the Section Molecular Immunology)

16 pages, 1066 KiB

Open AccessReview

The Impact of Alkaline Stress on Plant Growth and Its Alkaline Resistance Mechanisms

by Shuo Yang, Yiqing Xu, Zhenzhong Tang, Shumei Jin and Shuang Yang

Int. J. Mol. Sci. 2024, 25(24), 13719; https://doi.org/10.3390/ijms252413719 - 23 Dec 2024

Viewed by 941

Abstract

Alkaline stress can induce significant injury to plants, resulting in a range of negative effects, including ion toxicity, oxidative stress, and damage from high pH values. These stress factors can substantially affect normal plant growth and development, as well as yield and quality [...] Read more.

Alkaline stress can induce significant injury to plants, resulting in a range of negative effects, including ion toxicity, oxidative stress, and damage from high pH values. These stress factors can substantially affect normal plant growth and development, as well as yield and quality loss. To counteract alkaline stress, plants have developed a range of defense strategies, enabling them to adapt and thrive in challenging environments. These defense mechanisms operate at multiple levels such as morphological, physiological, biochemical, and molecular. The continuous advancement of genetic engineering has enabled significant breakthroughs in enhancing plant alkali resistance through human intervention. This research provides a scientific basis for crop production and ecological environment construction, and also promotes the effective development and utilization of saline-alkali lands, improving the sustainability of agricultural production. Full article

(This article belongs to the Special Issue Environmental Stress and Metabolic Responses in Plants)

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35 pages, 8312 KiB

Open AccessArticle

Comparison of the Effects of UV-C Light in the Form of Flash or Continuous Exposure: A Transcriptomic Analysis on Arabidopsis thaliana L.

by Seyed Mehdi Jazayeri, Jawad Aarrouf, Laurent Urban and Félicie Lopez-Lauri

Int. J. Mol. Sci. 2024, 25(24), 13718; https://doi.org/10.3390/ijms252413718 - 22 Dec 2024

Viewed by 822

Abstract

Ultraviolet C (UV-C) flash treatment represents a promising method for priming plants. This study compared the effects of 1 s (flash) and 60 s (60 s) UV-C exposures on the transcriptome of Arabidopsis thaliana L. plants. A dose of 200 J m⁻² [...] Read more.

Ultraviolet C (UV-C) flash treatment represents a promising method for priming plants. This study compared the effects of 1 s (flash) and 60 s (60 s) UV-C exposures on the transcriptome of Arabidopsis thaliana L. plants. A dose of 200 J m⁻² delivered in one second was observed to effectively stimulate plant defenses without causing any adverse effects on plant health. A total of 3054 and 1865 differentially expressed genes (DEGs) were identified in the flash and 60 s treatments, respectively, in comparison to the control plants. Of these, 1131 were common to both treatments. The flash treatment affected a greater number of transcription factors (415 genes) than the 60 s treatment (254 genes), indicating more pronounced alterations in gene expression. The flash treatment resulted in a significant overexpression of heat shock proteins (HSPs), heat shock factors (HSFs), and their associated genes, which impacted oxidative stress, proteostasis, genome stability, cell survival, and thermotolerance. The majority of mitochondrial genes were found to be upregulated, while photosynthetic genes exhibited a downregulation. These expression patterns coordinate electron transport and crosstalk between the nucleus, chloroplasts, and mitochondria, eliciting an adaptive protective response to UV-C flash. Additionally, the flash treatment resulted in alterations to several genes involved in cell cycle regulation, division, and DNA replication. These included ATP BMMs, BRCA2 s, IQDs, kinesin complex, MCM complex, CYCs, and CDKs, which ultimately led to cell cycle arrest as a temporary preparation for subsequent conditions. The present study demonstrates that a 1 s exposure to UV-C induces distinctive plant responses through coordinated gene expression. The findings suggest that the flash treatment is an innovative method that triggers a unique cellular response, prioritizing repair mechanisms and potentially enhancing plant immunity, resilience, and priming. It can be used as a plant resistance inducer and stimulator. Full article

(This article belongs to the Section Molecular Plant Sciences)

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