Search Results (243)

Sarcopenia is characterized by a reduction in muscle function and skeletal muscle mass relative to that of healthy individuals. In older adults and those who are less resistant to sarcopenia, glucocorticoid secretion or accumulation during treatment exacerbates muscle protein degradation, potentially causing sarcopenia. This study assessed the preventive effects and mechanisms of heat-killed Lactobacillus plantarum postbiotic beLP-K (beLP-K) against dexamethasone (DEX)-induced sarcopenia in C2C12 myotubes and Sprague-Dawley rats. The administration of beLP-K did not induce cytotoxicity and mitigated cell damage caused by DEX. Furthermore, beLP-K significantly reduced the expression of forkhead box O3 α (FoxO3α), muscle atrophy f-box (MAFbx)/atrogin-1, and muscle RING-finger protein-1 (MuRF1), which are associated with muscle protein degradation. DEX induced weight loss in rats; however, in the beLP-K group, weight gain was observed. Micro-computed tomography analysis revealed that beLP-K increased muscle mass, correlating with weight and grip strength. beLP-K alleviated the DEX-induced reduction in grip strength and increased the mass of hind leg muscles. The correlation between beLP-K administration and increased muscle mass was associated with decreased expression levels of muscle degradation-related proteins such as MAFbx/atrogin-1 and MuRF1. Therefore, beLP-K may serve as a treatment for sarcopenia or as functional food material. Full article

Topically applied TH1579 alleviated the psoriatic phenotype in the imiquimod-induced psoriasis mouse model by decreasing CD45⁺, Ly6b⁺, and CD3⁺ cell infiltration and downregulating the expression of the proliferation marker PCNA. Moreover, TH1579 strongly suppressed IL-17 expression in mouse skin, accompanied by reduced infiltration of IL-17-producing γδ-T cells. Furthermore, TH1579 decreased keratinocyte viability and proliferation. Mass spectrometry data analysis revealed the enrichment of proteins associated with nucleotide excision repair and cell cycle regulation. The key cell cycle regulatory protein F-box protein S-phase kinase-associated protein 2 (SKP2) was significantly downregulated, along with the psoriasis-associated proliferation marker WNT5a, identified as a SKP2 downstream target. The downregulation of SKP2 and WNT5a was confirmed in MTH1i-treated mouse skin. Our findings support the topical administration of MTH1i TH1579 as a psoriasis treatment. The therapeutic effects depended on the SKP2/WNT5a pathway, which mediates psoriatic hyperproliferation. This study introduces a conceptually innovative topical treatment for psoriasis patients with mild-to-moderate disease who have limited therapeutic options. Full article

Sarcopenia, the age-related loss of skeletal muscle mass and function, is associated with inflammation, mitochondrial dysfunction, and gut barrier impairment. This study investigates the postbiotic effects of heat-killed Lactiplantibacillus plantarum HY7715 (HY7715) and its extracellular vesicles (EVs) on muscle health and intestinal integrity. In C2C12 myotubes, both treatments enhanced myogenic differentiation by upregulating Myf5 and MYOG, and improved mitochondrial activity and biogenesis via increased PGC1α and mTOR expression. Under TNFα-induced muscle atrophy, they suppressed expression of atrophy-related markers (Fbox32, MuRF1, and myostatin). EVs showed stronger anti-inflammatory effects by reducing IL6 expression in muscle cells. In intestinal Caco-2 cells, HY7715-derived EVs improved barrier function by upregulating tight junction proteins (ZO-1, occludin, and claudins), and effectively reduced LPS-induced inflammation. These findings suggest that heat-killed HY7715 and its EVs may alleviate sarcopenia by enhancing muscle regeneration and maintaining intestinal homeostasis, highlighting their potential as safe, gut–muscle axis-targeting postbiotic interventions for healthy aging. Full article

Tubby-like proteins (TLPs) are essential multifunctional transcription factors in plants that significantly influence plant growth and development, signal transduction, and adaptation to environmental stress. Despite their importance, there is limited knowledge of the identification and functional roles of the TLP gene family in the common bean. In this study, we identified the PvTLP gene family, which consists of 10 PvTLP genes distributed unevenly across seven chromosomes. Phylogenetic analysis revealed that these genes could be classified into three subfamilies (A, B, and C). All PvTLP proteins contained both conserved tubby and F-box domains, with the exception of PvTLP7, which lacks the F-box domain. Conserved motif analysis revealed that 10 PvTLP genes contained motif 1 and motif 3. Cis-acting elements analysis indicated that PvTLP genes might be involved in light, hormone, and stress responses. Synteny analysis revealed a closer phylogenetic relationship between the common bean and dicotyledons than monocotyledons. qRT-PCR analysis confirmed the significant differences in the expression of most PvTLP genes in both leaves and roots under salt and drought stresses. These findings provide valuable insights for further exploration of the molecular functions of TLPs in plant responses to various stresses and offer key candidate genes for enhancing stress resistance in the common bean through molecular breeding. Full article

Anthocyanins, which accumulate in fruits, flowers, and vegetative organs, play a critical role in plant reproduction, disease resistance, stress tolerance, and promoting human health. Although light significantly influences the development of various fruit pigments, the specific mechanisms through which it regulates anthocyanin accumulation during fruit ripening are not yet fully understood. This study aimed to investigate the role of light in anthocyanin biosynthesis using Aft tomato fruits, which accumulate pigments in the epidermis. To explore the effects of light on anthocyanin biosynthesis, half of each fruit was covered with aluminum foil to establish light-exposed and bagged conditions for comparative analysis. The results showed that the bagged treatment led to a significant decrease in the total anthocyanin content of the fruits. Transcriptome analysis revealed a notable upregulation of several structural genes involved in the anthocyanin biosynthetic pathway, specifically Sl4CL, SlCHS, SlCHI, SlF3H, SlDFR, and Sl3GT in the light-exposed fruits. Additionally, the expression levels of light-responsive genes and transcription factors, such as SlCRY1, SlSPA, SlUVR3, SlHY5, SlBBX24, SlMYB11, MADS-box transcription factor 23, SlHD-ZIP I/II, SlAN2-like, SlbHLH and SlWD40 proteins, were significantly higher in the light-exposed samples compared to those subjected to the bagged treatment. Weighted Gene Co-Expression Network Analysis (WGCNA) demonstrated a strong association between light-induced gene expression such as SlPAL, SlCHS1, SlDFR, SlF3H, SlF3′5′H, SlANS, SlHY5, and SlAN2-like quantified by qRT-PCR analysis and anthocyanin biosynthesis. Moreover, as the fruit matured, both anthocyanin accumulation and the expression of genes related to its biosynthetic pathway increased. These findings contribute to a foundational understanding of the regulatory network that influences light-induced processes and fruit development impacting anthocyanin accumulation, which will facilitate in-depth study of the functions of these identified genes and provide a foundation for breeding anthocyanin-rich tomato varieties. Full article

YTH domain-containing proteins act as the primary readers of N⁶-methyladenosine (m⁶A), playing an important role in plant development and stress responses. However, little is known about the YTH proteins in medicinal plants. Genome-wide identification of the YTH gene family in the medicinal model plant, Salvia miltiorrhiza Bunge, identified a total of nineteen SmYTH genes from five chromosomes, with SmYTH8–SmYTH19 clustered on chromosome 8. Phylogenetic analysis showed that SmYTH proteins belong to the YTHDF category. No YTHDC members were identified. Conserved domain identification, amino acid sequence alignment, and phase separation prediction revealed that SmYTH1–SmYTH4 exhibited the characteristic m⁶A reader protein feature, containing conserved aromatic cages (WWW) capable of binding m⁶A residues. SmYTH5–SmYTH19 proteins contain a unique conserved F-box protein interaction domain that has not been reported previously. qRT-PCR analysis revealed tissue-specific patterns, with SmYTH1–SmYTH4 genes highly expressed in roots and leaves, whereas SmYTH8–SmYTH19 were mainly expressed in leaves. The results were consistent with RNA-seq data. The expression of various SmYTHs and the content of phenolic acid active ingredients were significantly altered under MeJA and SA treatments. The results provide useful information for further studies on the biological functions of m⁶A and YTH proteins in S. miltiorrhiza. Full article

Drought ranks among the key abiotic stresses that limit the growth and yield of grapevines (Vitis vinifera L.). Flavonols, a class of antioxidants commonly found in grapevines, play a crucial role in combating drought stress. In this study, we characterized the function and regulatory mechanism of the grapevine VviMYC4 in mediating flavonol biosynthesis in response to drought stress. VviMYC4 encodes a protein of 468 amino acids with conserved bHLH-MYC_N and bHLH domains. Phylogenetic analysis confirmed its homology with the grapevine VviMYC2 and similarity in function. The expression of VviMYC4 in ‘Cabernet Sauvignon’ grapevine seedling leaves increased initially and then decreased during prolonged drought stress. The homologous and heterologous transformation of VviMYC4 in grape suspension cells, Arabidopsis plants, tobacco leaves, and grapevine leaves demonstrated its ability to positively regulate flavonol biosynthesis and accumulation by promoting the expression of flavonol-related genes, thereby enhancing the drought tolerance of transgenic plants. Furthermore, VviMYC4 could bind to specific E-box sites on the promoters of VviF3H and VviFLS to improve their activities. This study highlights VviMYC4 as a pivotal positive regulator of drought tolerance in grapevines and proposes that VviMYC4 enhances the antioxidant and reactive oxygen species (ROS) scavenging abilities of grapevines in challenging environments and improves their stress resilience by mediating flavonol biosynthesis. Our findings offer crucial candidate genes and valuable insights for the molecular breeding of grapevine drought resistance. Full article

Pathogens deploy various molecular mechanisms to overcome host defenses, among which glycoside hydrolases (GHs) play a critical role as virulence factors. Understanding the functional roles of these enzymes is essential for uncovering pathogen–host interactions and developing strategies for disease management. Fusarium wilt has occurred in the main Piper nigrum cultivation regions, which seriously affects the yield and quality of P. nigrum. Here, we identified and characterized FsGH28c, a GH28 family member in Fusarium solani. Its expression was significantly upregulated during the infection of black pepper (Piper nigrum) roots by F. solani cv. WN-1, indicating its potential role in pathogenicity. FsGH28c elicited cell death in Nicotiana benthamiana and modulated the expression of genes related to pathogenesis. FsGH28c exerts a positive influence on the pathogenicity of F. solani. The knockout of FsGH28c mutant strains markedly attenuated F. solani ’s virulence in black pepper plants. The knockout mutant strains decrease the ability of F. solani to utilize carbon sources. The FsGH28c deletion did not affect mycelial growth on PDA but did impact spore development. We identified a U-box protein, PnPUB35, interacting with FsGH28c using yeast two-hybrid and bimolecular fluorescence complementation assays. PnPUB35 conferred enhanced resistance to F. solani in black pepper through positive regulation. These findings suggest that FsGH28c may function as a virulence factor by modulating host immune responses through its interaction with PnPUB35. Full article

Muscle atrophy leads to decreased muscle mass, weakness, inactivity, and increased mortality. E3 ubiquitin ligases, key regulators of protein degradation via the ubiquitin–proteasome system, play a critical role in atrophic mechanisms. This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and its objective was to evaluate the association between E3 ligases Muscle Atrophy F-box (MAFbx)/Atrogin-1 (Fbxo32) and Muscle RING-finger protein 1 (MuRF-1) (TRIM63) E3 ligase mRNA levels, reductions in skeletal muscle CSA measures, and atrophy conditions. We examined papers published on PubMed^®, Scopus, and Web of Science that studied E3 ligase gene expression signatures for Fbxo32 (MAFbx/Atrogin-1) and Trim63 (MuRF1) in different types of muscle atrophy and hypertrophy murine models. Twenty-nine studies selected by two independent raters were analyzed. Standardized mean differences (SMDs)/effect sizes (ESs) and 95% confidence intervals (CIs) were calculated for the outcomes using fixed-effects models. We found that 6- and 4.8-fold upregulation, respectively, of Fbxo32 and Trim63 was sufficient to reduce the ES to −3.89 (95% CI: −4.45 to −3.32) for the muscle fiber cross-sectional area and the development of skeletal muscle atrophy. I² and Q test statistics did not indicate heterogeneous data. There was a low probability of bias after both the funnel plot and Egger’s test analyses. These results were sustained independently of the atrophic model and muscle type. Therefore, the magnitude of the increase in muscle Fbxo32 and Trim63 mRNA is a feasible, reliable molecular marker for skeletal muscle atrophy in mice. The next step for the Ubiquitin-proteasome system (UPS) field involves elucidating the targets of E3 ligases, paving the way for diagnostic and treatment applications in humans. Full article

Waterlogging stress significantly impacts the growth and productivity of crops. As a traditional oil crop, sesame (Sesamum indicum L.) suffers substantial damage due to waterlogging stress. However, the mechanism underlying waterlogging stress in sesame is still unclear. In this study, we investigated the physiological indicators of two sesame genotypes under waterlogging stress. The results revealed that the activity of antioxidant enzymes in sesame was affected, with the contents of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) significantly increased. Additionally, transcriptional analysis identified a total of 15,143 differentially expressed genes (DEGs). Among them, 759 DEGs exhibited consistent differential expression across all time points, representing the core waterlogging-responsive genes. Gene Ontology (GO) enrichment analysis indicated that the DEGs were primarily associated with hypoxia, stimulus response, and oxidoreductase enzyme activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEGs were mainly enriched in the metabolic and biosynthesis of secondary metabolites, glycolysis/gluconeogenesis, phenylpropanoid biosynthesis, MAPK signaling pathway-plant, carbon fixation by Calvin cycle, plant hormone signal transduction, and plant-pathogen interaction pathways. Furthermore, transcription factors (TFs) such as AP2/ERF, bHLH, bZIP, and WRKY may play key roles in the transcriptional changes induced by waterlogging stress. Combined with weighted gene co-expression network analysis (WGCNA) analysis and K-means clustering, a total of 5 hub genes and 56 genes were identified, including F-box protein (Sin09950 and Sin12912), bZIP (Sin04465, Sin00091), WRKY (Sin01376, Sin06113), and so on. In brief, this study explored the regulatory network involved in waterlogging stress in sesame at the transcriptome level, providing valuable insights into unraveling the molecular mechanisms of waterlogging stress and facilitating the breeding of improved waterlogging-tolerant sesame varieties. Full article

This study evaluated the effects of α2-adrenergic agonist, prostaglandin F2α analog, and EP2 receptor agonist on tunicamycin-induced endoplasmic reticulum (ER) stress and fibrosis in human trabecular meshwork (TM) cells. Human TM cells were treated with tunicamycin for 24 h, followed by cotreatment with brimonidine (BRI), latanoprost (LAT), or omidenepag (OMD). Immunocytochemistry was used to assess expressions of collagen type I alpha 1 chain (COL1A1), fibronectin, F-actin, and alpha-smooth muscle actin (α-SMA). Western blotting was performed to evaluate levels of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and splicing X-box binding protein-1 (sXBP-1). Real-time qPCR was used to examine the mRNA expressions of COL1A1, connective tissue growth factor (CTGF), fibronectin, α-SMA, CHOP, GRP78, and sXBP-1. Expressions of COL1A1, CTGF, F-actin, fibronectin, α-SMA, CHOP, GRP78, and sXBP-1 significantly increased after tunicamycin treatment. BRI cotreatment significantly downregulated the mRNA and protein expressions of GRP78, and LAT or OMD cotreatment significantly reduced the CHOP and sXBP-1 expressions compared to the tunicamycin-treated group. BRI, LAT, or OMD cotreatment significantly attenuated cellular cytoskeletal changes and the increase of fibrosis markers such as COL1A1, CTGF, fibronectin, and α-SMA. In addition, COL1A1 mRNA expression was significantly lowered with LAT or OMD cotreatment compared to the BRI-cotreated group. Cotreatment with α2-adrenergic agonist, prostaglandin F2α analog, or EP2 receptor agonist alleviates tunicamycin-induced ER stress in human TM cells. Full article

The efficacy of sweet cherry production is highly dependent on the regularity of flowering events and genetic-determined relations between female sporophyte and male gametophyte, which became even more important with higher flowering temperatures caused by climate change. Special attention is paid to the genetic diversity that provides essential sources of potential temperature-tolerance genes. Our study aimed at the genetic and reproductive characterization of Balkan cherry cultivars of autochthonous origin (‘Canetova’, ‘G-2’, ‘Dolga Šiška’ and ‘Ohridska Crna’), and six potential pollenizers. To identify S-haplotypes, the polymerase chain reaction (PCR) method was used to detect the S-ribonuclease (S-RNase) and S-haplotype-specific F-box protein (SFB) alleles, combined with fragment analysis and S-RNase sequencing. Pollination experiments were performed at three Balkan localities over two flowering seasons, and the fluorescence microscopy method was used to assess the cultivars’ male/female reproductive behaviour. A novel S-RNase allele S₄₀ was identified in ‘Ohridska Crna’ for the first time. ‘Ohridska Crna’ also demonstrated the best adaptability to higher temperatures regarding primary ovule longevity. This feature makes it desirable from the aspect of breeding new cultivars that can withstand the impacts of climate change. The findings on male-female relations and their temperature dependence open up the possibility for yield prediction and smart horticultural decisions that can be made to guide cherry production. Full article

Phytaspases, plant cell death-promoting and proprotein-processing proteolytic enzymes of the plant subtilase family, display aspartate (caspase-like) cleavage specificity and a very unusual retrograde trafficking from the apoplast to the cell interior upon induction of death-inducing stresses. To determine the underlying molecular mechanisms, we performed a search for tobacco phytaspase (NtPhyt) interactors using an in vivo cross-linking approach in Nicotiana tabacum plants. Tobacco Tubby-like F-box protein 8 (named Tubic hereafter) was identified as an NtPhyt interactor, with formation of the cross-linked complex being only efficient under the oxidative stress conditions. Direct interaction of the two proteins was further corroborated in the in vitro experiments. Analysis of Tubic-EGFP behavior in plant cells revealed that Tubic is a membrane-associated and fairly unstable protein. Furthermore, we showed that NtPhyt and Tubic are capable of negatively affecting one another in plant cells. On the other hand, down-regulation of Tubic in Tubic-silenced plants impaired specifically the retrograde transport of NtPhyt upon the induction of oxidative stress, testifying to a critical role of Tubic in this process. Our study, thus, contributes to understanding of the mechanisms of NtPhyt retrograde trafficking in plant cells subjected to stress. Full article

Accumulating evidence suggests that the plasma membrane-localized phosphate transporter 1 (PHT1) family plays a fundamental role in the absorption, translocation, and re-mobilization of phosphorus in plants. Buckwheat (Fagopyrum spp.) exhibits high efficiency in phosphate uptake and wide adaptability to grow in under-fertilized soils. Despite their physiological importance, a systematic analysis of PHT1 genes in buckwheat has not been conducted yet. In this study, we performed a genome-wide identification and expression profile of the PHT1 gene family in Tartary buckwheat (Fagopyrum tataricum Gaertn). A total of eleven putative PHT1 genes (FtPHT1;1 to 1;11) were identified with an uneven distribution on all the F. tataricum chromosomes except for chromosomes 2, 3, and 5. All the FtPHT1s share the conserved domain GGDYPLSATIxSE, a typical signature of PHT1 transporters. A phylogenetic analysis indicated that FtPHT1 proteins could be clustered into four distinct subgroups, well supported by the exon–intron structure, consensus motifs, and the domain architecture. A gene duplication analysis suggested that tandem duplication may largely contribute to the expansion of the FtPHT1 gene family members. In silico predictions of cis-acting elements revealed that low-phosphate-responsive elements, such as W-box, P1BS, and MBS, were enriched in the promoter regions of FtPHT1 genes. Quantitative real-time PCR assays showed differential but partially overlapping expression patterns of some FtPHT1 genes in various organs under limited Pi supply and hormone stimuli, implying that these FtPHT1 transporters may be essential for Pi uptake, translocation, and re-mobilization, possibly through signaling cross-talk between the low phosphate and hormones. These observations provide molecular insights into the FtPHT1 gene family, which paves the way to a functional analysis of FtPHT1 members in the future. Full article

Objectives: Kajiichigoside F1 and rosamultin are natural triterpenoid saponins found in the root of Rosa laevigata Michx. These compounds are isomers, making their separation challenging. Nonetheless, they have been reported to exhibit significant anti-inflammatory activity, although their mechanism of action remains unclear. This study aimed to optimize the extraction process of echinacoside and rosamultin from R. laevigata and to elucidate the anti-inflammatory mechanisms of these saponins in an LPS-induced acute lung injury (ALI) model. Methods: The extraction process was optimized using a single-factor experiment and the Box–Behnken response surface methodology, with the content of kajiichigoside F1, rosamultin, and their total content serving as evaluation indices. The acute lung injury model was induced by LPS, and lung tissue damage was assessed through hematoxylin and eosin (HE) staining. The secretion of relevant inflammatory factors was quantified using enzyme-linked immunosorbent assay (ELISA), and the expression levels of associated proteins were analyzed via Western blotting. Results: The optimal extraction conditions were determined to be an ethanol volume fraction of 80.0%, a solid–liquid ratio of 1:25, an extraction duration of 80 min, and three extraction cycles. Kajiichigoside F1 and rosamultin were found to mitigate alveolar inflammation in mice with acute lung injury (ALI) by effectively reducing the expression of the pro-inflammatory cytokines TNF-α and IL-6. Additionally, these compounds down-regulated the expression of phosphorylated NF-κB p65 and NF-κB IκBα proteins, thereby alleviating inflammatory symptoms. Conclusions: Kajiichigoside F1 and rosamultin attenuate the inflammatory response in acute lung injury induced by lipopolysaccharide (LPS) stimulation through modulation of the NF-κB signaling pathway. This study preliminarily elucidates their anti-inflammatory mechanism, suggesting that both compounds possess therapeutic potential for ALI. These findings provide significant guidance for the future development of active components derived from the root of R. laevigata and establish a foundation for enhancing the quality standards of its medicinal materials. Full article