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Keywords = related gene expression

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19 pages, 3849 KB  
Article
Gibberellin-Treated Seedless Cultivation Alters Berry Fracture Behavior, Cell Size and Cell Wall Components in the Interspecific Hybrid Table Grape (Vitis labruscana × Vitis vinifera) ‘Shine Muscat’
by Hikaru Ishikawa, Kaho Masuda and Tomoki Shibuya
Plants 2026, 15(2), 287; https://doi.org/10.3390/plants15020287 (registering DOI) - 17 Jan 2026
Abstract
Gibberellin (GA)-based seedless cultivation is widely used in the skin-edible interspecific table grape (Vitis labruscana × Vitis vinifera) ‘Shine Muscat’, yet when and how GA treatment reshapes fracture-type texture during berry development remains unclear. This study aimed to identify developmental stages [...] Read more.
Gibberellin (GA)-based seedless cultivation is widely used in the skin-edible interspecific table grape (Vitis labruscana × Vitis vinifera) ‘Shine Muscat’, yet when and how GA treatment reshapes fracture-type texture during berry development remains unclear. This study aimed to identify developmental stages and tissue/cell-wall features associated with GA-dependent differences in berry fracture behavior. We integrated intact-berry fracture testing at harvest (DAFB105), quantitative histology of pericarp/mesocarp tissues just before veraison (DAFB39) and at harvest, sequential cell-wall fractionation assays targeting pectin-rich (uronic acid) and hemicellulose/cellulose-related pools at cell division period, cell expansion period and harvest, and stage-resolved RNA-Seq across the same three developmental stages. GA-treated berries had a larger diameter and showed a higher fracture load and a lower fracture strain than non-treated berries at harvest, while toughness did not differ significantly. Histology revealed thicker pericarp tissues and lower mesocarp cell density in GA-treated berries, together with increased cell-size heterogeneity and enhanced radial cell expansion. Cell wall analyses showed stage-dependent decreases in uronic acid contents in water-, EDTA-, and Na2CO3-soluble fractions in GA-treated berries. Transcriptome profiling indicated GA-responsive expression of putative cell expansion/primary-wall remodeling genes, EXORDIUM and xyloglucan endotransglucosylase/hydrolases, at DAFB24 and suggested relatively enhanced ethylene-/senescence-associated transcriptional programs together with pectin-modifying related genes, Polygaracturonase/pectate lyase and pectin methylesterase, in non-treated mature berries. Collectively, GA treatment modifies mesocarp cellular architecture and pectin-centered wall status in a stage-dependent manner, providing a tissue- and cell wall–based framework for interpreting fracture-related texture differences under GA-based seedless cultivation in ‘Shine Muscat’. Full article
(This article belongs to the Special Issue Fruit Development and Ripening)
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15 pages, 5795 KB  
Article
Identification and Analysis of the Terpene Synthases (TPS) Gene Family in Camellia Based on Pan-Genome
by Renjie Yin, Haibin Liu, Shanyuanrui Lin, Zhuolin Li, Linna Ma and Peng Liu
Genes 2026, 17(1), 94; https://doi.org/10.3390/genes17010094 (registering DOI) - 17 Jan 2026
Abstract
Terpenes are major determinants of tea aroma, and terpene synthases (TPSs) catalyze key steps in terpenoid biosynthesis. To capture gene-family variation beyond a single reference, we performed a pan-genome–based analysis of TPS genes across nine Camellia genomes (three wild tea relatives and six [...] Read more.
Terpenes are major determinants of tea aroma, and terpene synthases (TPSs) catalyze key steps in terpenoid biosynthesis. To capture gene-family variation beyond a single reference, we performed a pan-genome–based analysis of TPS genes across nine Camellia genomes (three wild tea relatives and six cultivated Camellia sinensis accessions) and integrated pan-transcriptome profiling across eight tissues. We identified 381 TPS genes; wild species contained more TPSs than cultivated accessions (mean 58.3 vs. 34.3), suggesting a putative contraction. Phylogenetic analysis with Arabidopsis TPSs classified Camellia TPSs into five subfamilies, dominated by TPS-b (149) and TPS-a (140), whereas TPS-c was rare (8). Gene-structure and physicochemical analyses revealed marked subfamily divergence, with TPS-c showing highly conserved coding-region length. Orthology clustering assigned 355 TPSs to 19 orthogroups, including five core groups (190 genes, 53.5%) and 14 dispensable groups (165 genes, 46.5%); core/non-core status was significantly associated with subfamily composition. Tandem and proximal duplication contributed most to TPS expansion (29.4% and 29.1%), and all orthogroups exhibited copy-number variation, with pronounced lineage-specific expansions. Ka/Ks analyses indicated pervasive purifying selection (median 0.516) but heterogeneous constraints among subfamilies. Finally, cultivated tea showed higher TPS expression in most tissues, especially mature leaf and stem, and TPS-g displayed the broadest and strongest expression. Together, these results provide a pan-genome resource for Camellia TPSs and highlight how domestication, duplication, and CNV shape terpene-related genetic diversity. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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16 pages, 3024 KB  
Article
CDE6 Regulates Chloroplast Ultrastructure and Affects the Sensitivity of Rice to High Temperature
by Shihong Yang, Biluo Li, Pan Qi, Wuzhong Yin, Liang Xu, Siqi Liu, Chiyu Wang, Xiaoqing Yang, Xin Gu and Yungao Hu
Plants 2026, 15(2), 284; https://doi.org/10.3390/plants15020284 (registering DOI) - 17 Jan 2026
Abstract
Chloroplasts are key organelles in plants that carry out photosynthesis, convert light energy into chemical energy, and synthesize organic compounds. In this study, a stably heritable chlorophyll-deficient mutant was screened from the ethyl methanesulfonate-induced mutation library of Wuyunjing 21 (WYJ21). This mutant was [...] Read more.
Chloroplasts are key organelles in plants that carry out photosynthesis, convert light energy into chemical energy, and synthesize organic compounds. In this study, a stably heritable chlorophyll-deficient mutant was screened from the ethyl methanesulfonate-induced mutation library of Wuyunjing 21 (WYJ21). This mutant was designated as chlorophyll deficient 6 (cde6). The cde6 mutant exhibits a low chlorophyll content, photosynthetic defects, an impaired chloroplast structure, a significant reduction in the number of stacked thylakoid layers, and a yellow-green leaf phenotype in the early tillering stage. Through MutMap analysis, it was found that the cde6 mutant harbors a single-base mutation (T→A) in the LOC_Os07g38300 gene. This mutation results in an amino acid substitution from valine (Val) to aspartic acid (Asp) in the encoded protein, thereby affecting the protein’s structure and function. The mutation of CDE6 leads to decreased expression of genes related to chloroplast development and chlorophyll biosynthesis. Further studies revealed that the CDE6, a potential chloroplast ribosome recycle factor, leads to high temperature sensitivity in rice when mutated. As high-temperature stress is a primary constraint to global rice productivity, the identification of CDE6 provides a genetic target for improving thermotolerance. In conclusion, these findings demonstrate that CDE6 plays a crucial role in chloroplast biogenesis and provide new insights into its regulatory function in high-temperature tolerance. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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20 pages, 3094 KB  
Article
The PIN-LIKES Auxin Transport Genes Involved in Regulating Yield in Soybean
by Siming Wei, Jiayin Han, Chun Tang, Lei Zhang, Mingliang Yang, Fubin Cao, Yuyao Zhao, Xinghua Li, Hao Xu, Zhaoming Qi and Qingshan Chen
Agronomy 2026, 16(2), 226; https://doi.org/10.3390/agronomy16020226 (registering DOI) - 17 Jan 2026
Abstract
PIN-LIKES (PILS) auxin transport genes play key roles in plant development, but their functions and molecular mechanism in soybean yield remain unclear. Here, we characterized the 44-member soybean GmPILS genes via comprehensive analyses. Phylogenetic analysis classified GmPILS into three subfamilies, with [...] Read more.
PIN-LIKES (PILS) auxin transport genes play key roles in plant development, but their functions and molecular mechanism in soybean yield remain unclear. Here, we characterized the 44-member soybean GmPILS genes via comprehensive analyses. Phylogenetic analysis classified GmPILS into three subfamilies, with most proteins being hydrophobic, stable, and membrane-localized. Chromosomal distribution showed random scattering across 17 chromosomes, with gene duplication driving family expansion. Expression profiling identified GmPILS36 and GmPILS40 as seed-specific and differentially expressed between cultivated Suinong14 (SN14) and wild ZYD00006 (ZYD06) soybeans. Population genetic analyses revealed GmPILS40 experienced a domestication bottleneck without yield-related superior haplotypes, while GmPILS36 underwent selection during landrace-to-improved variety domestication. A coding region CC/TT natural variation in GmPILS36 (S/A substitution) was significantly associated with seed weight per plant and 100-seed weight, with the TT genotype conferring superior traits. This study provides insights into GmPILS genes’ evolution and identifies GmPILS36 as an important candidate gene for further functional study and investigation of the molecular mechanisms regulating soybean yield. Full article
(This article belongs to the Special Issue Functional Genomics and Molecular Breeding of Soybeans—2nd Edition)
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23 pages, 2243 KB  
Article
Transcriptional Modulation in Grapevine by a Biostimulant Treatment for Improved Plant Resilience to Stress Events
by Asia Mostacci, Domenico Di Cosmo, Ornella Incerti, Antonio Ippolito, Rita Milvia De Miccolis Angelini and Simona Marianna Sanzani
Plants 2026, 15(2), 283; https://doi.org/10.3390/plants15020283 (registering DOI) - 17 Jan 2026
Abstract
Grapevine (Vitis vinifera L.) is a globally significant crop increasingly affected by a variety of biotic and abiotic stresses. Plant biostimulants offer a promising approach to enhance plant resilience by modulating key physiological and metabolic processes. This study aimed to demonstrate that [...] Read more.
Grapevine (Vitis vinifera L.) is a globally significant crop increasingly affected by a variety of biotic and abiotic stresses. Plant biostimulants offer a promising approach to enhance plant resilience by modulating key physiological and metabolic processes. This study aimed to demonstrate that the preventive application of a Fabaceae-based biostimulant can prime grapevine defense pathways, thereby improving plants’ ability to endure potential stress conditions. Indeed, resistance to both biotic and abiotic stresses in plants involves common pathways, including Ca2+ and ROS signaling, MAPK cascades, hormone cross-talk, transcription factor activation, and induction of defense genes. Grapevine leaves were subjected to high-throughput transcriptomic analysis coupled with qPCR validation 6 and 24 h following treatment application. Differentially expressed genes were visualized using MapMan to identify the major metabolic and signaling pathways responsive to the treatment. This integrative analysis revealed several defense-related pathways triggered by the biostimulant, with representative protein families showing both up- and downregulation across key functional categories. Overall, the results indicate that a wider array of pathways associated with stress tolerance and growth regulation were stimulated in treated plants compared to untreated controls. These findings support the conclusion that a preventive biostimulant application can effectively prime grapevine metabolism, enhancing its preparation to cope with forthcoming environmental challenges. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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13 pages, 853 KB  
Article
Dysregulated MicroRNAs in Parkinson’s Disease: Pathogenic Mechanisms and Biomarker Potential
by Yasemin Ünal, Dilek Akbaş, Çilem Özdemir and Tuba Edgünlü
Int. J. Mol. Sci. 2026, 27(2), 930; https://doi.org/10.3390/ijms27020930 (registering DOI) - 17 Jan 2026
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal α-synuclein aggregation. Circulating microRNAs (miRNAs) have emerged as promising biomarkers and potential modulators of PD-related molecular pathways. In this study, we investigated the expression levels of four candidate [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal α-synuclein aggregation. Circulating microRNAs (miRNAs) have emerged as promising biomarkers and potential modulators of PD-related molecular pathways. In this study, we investigated the expression levels of four candidate miRNAs—miR-15a-5p, miR-16-5p, miR-139-5p, and miR-34a-3p—in patients with PD compared with healthy controls. A total of 47 PD patients and 45 age- and sex-matched controls were enrolled. Plasma miRNA levels were quantified using standardized RNA extraction, cDNA synthesis, and qPCR protocols. We observed marked upregulation of miR-15a-5p and robust downregulation of both miR-139-5p and miR-34a-3p in PD patients, whereas miR-16-5p showed no significant difference between groups. Target gene prediction and functional enrichment analysis identified 432 unique genes, with enrichment in biological processes related to protein ubiquitination and catabolic pathways, and signaling cascades such as mTOR, PI3K-Akt, MAPK, and Hippo pathways, all of which are implicated in neurodegeneration. Elevated miR-15a-5p may contribute to pro-apoptotic mechanisms, while reduced miR-139-5p and miR-34a-3p expression may reflect impaired mitochondrial function, diminished neuroprotection, or compensatory regulatory responses. Together, these dysregulated circulating miRNAs provide novel insight into PD pathophysiology and highlight their potential as accessible, non-invasive biomarkers. Further longitudinal studies in larger and more diverse cohorts are warranted to validate their diagnostic and prognostic value and to explore their utility as therapeutic targets. Full article
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13 pages, 4569 KB  
Article
Transcriptomic Insights into the Molecular Responses of Red Imported Fire Ants (Solenopsis invicta) to Beta-Cypermethrin and Cordyceps cicadae
by Ruihang Cai, Xiaola Li, Yiqiu Chai, Zhe Liu, Yihu Pan and Yougao Liu
Genes 2026, 17(1), 92; https://doi.org/10.3390/genes17010092 (registering DOI) - 17 Jan 2026
Abstract
Background: Solenopsis invicta, commonly known as the red imported fire ant (RIFA), is an important global invasive pest, and its management is challenging because of insecticide resistance and environmental problems. Methods: In this research, we applied transcriptomics to analyze the molecular responses [...] Read more.
Background: Solenopsis invicta, commonly known as the red imported fire ant (RIFA), is an important global invasive pest, and its management is challenging because of insecticide resistance and environmental problems. Methods: In this research, we applied transcriptomics to analyze the molecular responses of S. invicta worker ants exposed to different types of pesticides, beta-cypermethrin (BC) and the entomopathogenic fungus Cordyceps cicadae (CC), as well as to different concentrations of these pesticides. Results: A total of 2727 differentially expressed genes (DEGs) were identified across all samples. The number of DEGs in the BC treatment group was significantly higher than that in the CC treatment group (2520 vs. 433), and higher concentrations resulted in more DEGs (an increase of 47 in the BC group and 229 in the CC group). KEGG pathway analysis revealed that the DEGs were significantly enriched in lipid metabolism, carbohydrate metabolism, amino acid metabolism, signal transduction, and membrane transport. Immune-related gene analysis showed more general down-regulation (average FPKM value in BC 741.37 to 756.06 vs. CK 1914.42) of pathogen recognition genes (PGRP-SC2) under BC stress conditions, while CC treatment resulted in increases in expression of important immune effectors such as various serine proteases. Conclusions: Overall, this study provides useful insights into the molecular basis of responses to different pesticides in S. invicta and offers a basis to develop new approaches to control this pest. Full article
(This article belongs to the Section Bioinformatics)
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23 pages, 3599 KB  
Article
Antioxidant Intervention in NAFLD: Astaxanthin and Kokum Modulate Redox Status and Lysosomal Degradation
by Natalia Ksepka, Natalia Kuzia, Sara Frazzini, Luciana Rossi, Małgorzata Łysek-Gładysińska, Michał Ławiński and Artur Jóźwik
Molecules 2026, 31(2), 321; https://doi.org/10.3390/molecules31020321 (registering DOI) - 16 Jan 2026
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article
(This article belongs to the Special Issue Antioxidant, and Anti-Inflammatory Activities of Natural Plants)
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23 pages, 1041 KB  
Article
Dietary Green-Algae Chaetomorpha linum Extract Supplementation on Growth, Digestive Enzymes, Antioxidant Defenses, Immunity, Immune-Related Gene Expression, and Resistance to Aeromonas hydrophila in Adult Freshwater Snail, Bellamya bengalensis
by Hairui Yu, Govindharajan Sattanathan, Mansour Torfi Mozanzadeh, Pitchai Ruba Glory, Swaminathan Padmapriya, Thillainathan Natarajan, Ramasamy Rajesh and Sournamanikam Venkatalakshmi
Animals 2026, 16(2), 289; https://doi.org/10.3390/ani16020289 (registering DOI) - 16 Jan 2026
Abstract
Macroalgae plays a significant role in the formulation of innovative and environmentally sustainable approaches to address food challenges. Specifically, green macroalgae serve as dietary supplements aimed at improving the health, growth, and feeding efficiency of various species of marine and freshwater fishes, as [...] Read more.
Macroalgae plays a significant role in the formulation of innovative and environmentally sustainable approaches to address food challenges. Specifically, green macroalgae serve as dietary supplements aimed at improving the health, growth, and feeding efficiency of various species of marine and freshwater fishes, as well as mollusks. The effects of Chaetomorpha linum extract (CLE) on growth performance, physiological responses, and disease resistance are studied in Bellamya bengalensis against Aeromonas hydrophila. In this experiment, adult B. bengalensis (4412 ± 165.25 mg) were randomly divided into 15 rectangular glass aquariums (35 snail/aquaria; 45 L capacity) and their basal diet was supplemented with different levels of CLE, including 0 (CLE0), 1 (CLE1), 2 (CLE2), 3 (CLE3), and 4 (CLE4) g/kg for 60 days. The growth performance in the CLE3 dietary group was significantly higher that of the CLE0 group, exhibiting both linear and quadratic trends in relation to dietary CLE levels (p < 0.05). The activities of pepsin, amylase, and lipase were found to be highest in CLE3 and lowest in CLE0. Both linear and quadratic responses to dietary CLE levels in digestive enzymes were observed (p < 0.05). The activities of superoxide dismutase and catalase in the hepatopancreas were found to be elevated in snails due to the synergistic effect of the supplemented CLE diet. Among different levels of diet given, CLE2-supplemented snails showed an increase in their enzyme activity (p < 0.05). Interestingly, all the CLE-treated snails expressed elevated levels of mucus lysozyme and mucus protein when compared to control (p < 0.05). Additionally, hepatopancreatic acid phosphatase and alkaline phosphatase activity were elevated in snails consuming CLE3 (p < 0.05). The transcription levels of immune-related genes, including mucin-5ac and cytochrome, were significantly elevated in snails that were fed a diet supplemented with 2–4 g of CLE/kg. Furthermore, the transcription level of the acid phosphatase-like 7 protein gene also increased in snails receiving CLE-supplemented diets. After a 14-day period of infection, snails that consumed a diet supplemented with 3–4 g/kg of CLE exhibited a notable increase in survival rates against virulent A. hydrophila. Based on the above findings, it is suggested that a diet supplemented with 3 g/kg of CLE may enhance growth, antioxidant and immune defense, and disease resistance in the freshwater snail B. bengalensis. Full article
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12 pages, 3774 KB  
Article
Gene Expression Profiles of Melanocytes Over-Expressing miR-5110 in Alpaca
by Shanshan Yang, Dingxing Jiao, Fengsai Li, Xuqi Wang, Tao Song, Lili Wang, Ping Rui and Zengjun Ma
Curr. Issues Mol. Biol. 2026, 48(1), 93; https://doi.org/10.3390/cimb48010093 (registering DOI) - 16 Jan 2026
Abstract
Previous studies have shown that miR-5110 regulates pigmentation by cotargeting melanophilin (MLPH) and WNT family member 1 (WNT1). In order to find the possible molecular mechanism for pigmentation, we examined the mRNA expression profiles in melanocytes of alpaca transfected with miR-5110, inhibitor or [...] Read more.
Previous studies have shown that miR-5110 regulates pigmentation by cotargeting melanophilin (MLPH) and WNT family member 1 (WNT1). In order to find the possible molecular mechanism for pigmentation, we examined the mRNA expression profiles in melanocytes of alpaca transfected with miR-5110, inhibitor or negative control (NC) plasmids using high-throughput RNA sequencing. The results showed that a total of 91,976 unigenes were assembled from the reads, among which 13,262 had sequence sizes greater than 2000 nucleotides. According to the KEGG pathway analysis, four pathways related to melanogenesis, the MAPK signaling pathway, Wnt signaling pathway, and cAMP signaling pathway were identified. Compared to the NC, 162 gene were upregulated and 41 genes were downregulated in melanocytes over expressed by miR-5110. The differential expressions of mRNAs Dickkopf 3 (DKK3), premelanosome protein (Pmel), insulin-like growth factor 1 receptor (IGF1R), cyclin-dependent kinase 5 (CDK5), endothelin receptor type B (Ednrb), kit ligand (Kitl), Myc, and S100 were verified using qRT-PCR, which agreed with the results of RNA sequencing. We also verified the differential expressions of mRNAs of some genes in the MAPK signaling pathway using qRT-PCR, which agreed with the results of RNA sequencing. Interestingly, several genes were screened as candidates for the melanogenesis regulated by miR-5110, including Kitl and MAPK-activated protein kinase 3 (MAPKAPK3). These findings provide new insights for further molecular studies on the effects of miR-5110 on the melanogenesis and pigmentation. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
26 pages, 5913 KB  
Article
Differential Regulatory Effects of Cannabinoids and Vitamin E Analogs on Cellular Lipid Homeostasis and Inflammation in Human Macrophages
by Mengrui Li, Sapna Deo, Sylvia Daunert and Jean-Marc Zingg
Antioxidants 2026, 15(1), 119; https://doi.org/10.3390/antiox15010119 (registering DOI) - 16 Jan 2026
Abstract
Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the [...] Read more.
Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the regulatory effects on the expression of genes involved in cellular lipid homeostasis (e.g., CD36/FAT cluster of differentiation/fatty acid transporter and scavenger receptor SR-B1) and inflammation (e.g., inflammatory cytokines, TNFα, IL1β) by cannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) in human THP-1 macrophages with/without co-treatment with natural alpha-tocopherol (RRR-αT), natural RRR-αTA (αTAn), and synthetic racemic all-rac-αTA (αTAr). In general, αTAr inhibited both lipid accumulation and the inflammatory response (TNFα, IL6, IL1β) more efficiently compared to αTAn. Our results suggest that induction of CD36/FAT mRNA expression after treatment with THC can be prevented, albeit incompletely, by αTA (either αTAn or αTAr) or CBD. A similar response pattern was observed with genes involved in lipid efflux (ABCA1, less with SR-B1), suggesting an imbalance between uptake, metabolism, and efflux of lipids/αTA, increasing macrophage foam cell formation. THC increased reactive oxygen species (ROS), and co-treatment with αTAn or αTAr only partially prevented this. To study the mechanisms by which inflammatory and lipid-related genes are modulated, HEK293 cells overexpressing cannabinoid receptors (CB1 or TRPV-1) were transfected with luciferase reporter plasmids containing the human CD36 promoter or response elements for transcription factors involved in its regulation (e.g., LXR and NFκB). In cells overexpressing CB1, we observed activation of NFκB by THC that was inhibited by αTAr. Full article
(This article belongs to the Special Issue Health Implications of Vitamin E and Its Analogues and Metabolites)
11 pages, 817 KB  
Article
Cyclic ADP-Ribose Modulates Intracellular Calcium Homeostasis and Anagen-Associated Signaling Pathways in Human Hair Follicle Dermal Papilla Cells
by Jihwan Shin, Migyoung Yang and Geunsik Jung
Appl. Sci. 2026, 16(2), 950; https://doi.org/10.3390/app16020950 - 16 Jan 2026
Abstract
Background: Hair loss (alopecia) is primarily driven by the premature transition of hair follicles from the anagen (growth) to the catagen (regression) phase. Intracellular calcium signaling is implicated in hair follicle biology, including the regulation of Wnt/β-catenin activity and the modulation of [...] Read more.
Background: Hair loss (alopecia) is primarily driven by the premature transition of hair follicles from the anagen (growth) to the catagen (regression) phase. Intracellular calcium signaling is implicated in hair follicle biology, including the regulation of Wnt/β-catenin activity and the modulation of catagen-associated factors such as TGF-β2. Cyclic ADP-ribose (cADPR), a calcium-mobilizing second messenger synthesized by CD38, has recently emerged as a potential modulator of intracellular calcium dynamics. This study investigated whether cADPR is associated with changes in intracellular calcium retention and anagen-associated signaling pathways in human hair follicle dermal papilla cells (HHDPCs). Methods: HHDPCs were treated with cADPR (0.001–0.5 ppm) and analyzed for cell viability, intracellular calcium retention, β-catenin-dependent transcription, and the gene expression of LEF-1 and TGF-β2. Cell viability was evaluated using the MTT assay, intracellular calcium content was quantified by ICP–OES, β-catenin activation was assessed using a TOPFlash luciferase assay, and gene expression was measured by qRT-PCR. Results: cADPR did not induce marked cytotoxicity, maintaining more than 98% cell viability across all concentrations. The highest response was observed at 0.05 ppm, at which intracellular calcium content remained elevated for up to six hours as assessed by ICP–OES. At this concentration, β-catenin-dependent transcription increased by approximately 2.3-fold relative to control, LEF-1 expression was significantly upregulated (~2.5-fold), and TGF-β2 expression was significantly downregulated (~0.3-fold). These responses showed an overall concentration-dependent trend across assays. Conclusions: These findings indicate an association between cADPR treatment and modulation of intracellular calcium retention and anagen-related signaling readouts in HHDPCs, supporting the need for further studies to establish mechanistic causality and physiological relevance. Full article
14 pages, 1856 KB  
Article
Autophagy Activation in Mesenchymal Stem Cells with Lithium Chloride and Trehalose: Implications for Regenerative Medicine
by Ali Fouad, Yasser ElSherbini, Elsayed Abdelhady and Mohamed Abdraboh
BioMed 2026, 6(1), 4; https://doi.org/10.3390/biomed6010004 - 16 Jan 2026
Abstract
Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in [...] Read more.
Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article
35 pages, 2832 KB  
Article
Dietary Methionine Supplementation Improves Rainbow Trout (Oncorhynchus mykiss) Immune Responses Against Viral Haemorrhagic Septicaemia Virus (VHSV)
by Mariana Vaz, Gonçalo Espregueira Themudo, Inês Carvalho, Felipe Bolgenhagen Schöninger, Carolina Tafalla, Patricia Díaz-Rosales, Benjamín Costas and Marina Machado
Biology 2026, 15(2), 163; https://doi.org/10.3390/biology15020163 - 16 Jan 2026
Abstract
Several studies have demonstrated that methionine supplementation in fish diets enhances immune status, inflammatory response, and resistance to bacterial infections by modulating for DNA methylation, aminopropylation, and transsulfuration pathways. However, the immunomodulatory effects of methionine in viral infections remain unexplored. This study aimed [...] Read more.
Several studies have demonstrated that methionine supplementation in fish diets enhances immune status, inflammatory response, and resistance to bacterial infections by modulating for DNA methylation, aminopropylation, and transsulfuration pathways. However, the immunomodulatory effects of methionine in viral infections remain unexplored. This study aimed to evaluate the effect of methionine supplementation on immune modulation and resistance to the viral haemorrhagic septicaemia virus (VHSV) in rainbow trout (Oncorhynchus mykiss). Two diets were formulated and fed to juvenile rainbow trout for four weeks: a control diet (CTRL) with all nutritional requirements, including the amino acid profile required for the species, and a methionine-supplemented diet (MET), containing twice the normal requirement of DL-methionine. After feeding, fish were bath-infected with VHSV, while control fish were exposed to a virus-free bath. Samples were collected at 0 (after feeding trial), 24, 72, and 120 h post-infection for the haematological profile, humoral immune response, oxidative stress, viral load, RNAseq, and gene expression analysis. In both diets, results showed a peak in viral activity at 72 h, followed by a reduction in viral load at 120 h, indicating immune recovery. During the peak of infection, leukocytes, thrombocytes, and monocytes migrated to the infection site, while oxidative stress biomarkers (superoxide dismutase glutathione S-transferase, and glutathione redox ratio) suggested a compromised ability to manage cellular imbalance due to intense viral activity. At 120 h, immune recovery and homeostasis were observed due to an increase in the amount of nitric oxide, GSH/GSSG levels, leukocyte replacement, monocyte influx, and a reduction in the viral load. When focusing on the infection peak, gene ontology (GO) analysis showed several exclusively enriched pathways in the skin and gills of MET-fed fish, driven by the upregulation of several key genes. Genes involved in recognition/signalling, inflammatory response, and other genes with direct antiviral activity, such as TLR3, MYD88, TRAF2, NF-κB, STING, IRF3, -7, VIG1, caspases, cathepsins, and TNF, were observed. Notably, VIG1 (viperin), a key antiviral protein, was significantly upregulated in gills, confirming the modulatory role of methionine in inducing its transcription. Viperin, which harbours an S-adenosyl-L-methionine (SAM) radical domain, is directly related to methionine biosynthesis and plays a critical role in the innate immune response to VHSV infection in rainbow trout. In summary, this study suggests that dietary methionine supplementation can enhance a more robust fish immune response to viral infections, with viperin as a crucial mediator. The improved antiviral readiness observed in MET-fed fish underscores the potential of targeted nutritional adjustments to sustain fish health and welfare in aquaculture. Full article
(This article belongs to the Section Immunology)
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31 pages, 1615 KB  
Article
From Antioxidant Defenses to Transcriptomic Signatures: Concentration-Dependent Responses to Polystyrene Nanoplastics in Reef Fish
by Manuela Piccardo, Mirko Mutalipassi, Lucia Pittura, Rosa Maria Sepe, Pasquale De Luca, Laurence Besseau, Monia Renzi, Stefania Gorbi, Vincent Laudet, Alberto Pallavicini, Paolo Sordino and Antonio Terlizzi
Microplastics 2026, 5(1), 14; https://doi.org/10.3390/microplastics5010014 - 16 Jan 2026
Abstract
Nanoplastics (NPs) pose significant risks due to their small size and ability to penetrate biological tissues. However, the molecular pathways and cellular mechanisms affected by NP exposure in marine teleosts remain poorly understood, especially in tropical reef fishes. This study examined the impact [...] Read more.
Nanoplastics (NPs) pose significant risks due to their small size and ability to penetrate biological tissues. However, the molecular pathways and cellular mechanisms affected by NP exposure in marine teleosts remain poorly understood, especially in tropical reef fishes. This study examined the impact of short-term (7 days) waterborne exposure of 100 nm-carboxyl-modified polystyrene NPs on the false clownfish (Amphiprion ocellaris) exposed at two daily concentrations: low (20 µg/L, environmentally relevant) and high (2000 µg/L). A multidisciplinary approach, including biochemical and transcriptomic analyses, was conducted to assess toxic effects. Biochemical assays revealed limited changes in antioxidant defenses (CAT, GR, GST, TOSC). However, the Integrated Biomarker Response index (IBRv2i) suggested a compromised physiological condition, supported by transcriptomic data. Transcriptomic profiling revealed 409 significantly differentially expressed genes (DEGs) in the high-concentration and 354 DEGs in the low-concentration groups, with 120 shared DEGs mostly upregulated and indicative of a core molecular response. Collectively, the transcriptional profile of the low-concentration group resembled an early-warning, energy-reallocation strategy aimed at preserving essential sensory functions while minimizing expendable functions. The high-concentration group amplified the shared stress signature and recruited an additional 289 unique genes, resulting in pronounced enrichment of Gene Ontology terms related to “muscle contraction”, “oxygen transport”, “hydrogen-peroxide catabolism”, and “extracellular-matrix”. This study demonstrates that PS-NP exposure can alter gene expression and physiology in juvenile reef fish, even at environmentally relevant concentrations. Molecular responses varied with concentrations highlighting the role of exposure level in influencing biological systems and potential long-term impacts of NP pollution in marine environments. Full article
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