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Frontiers in Immunology 2024The innate immune system of insects can respond more swiftly and efficiently to pathogens based on previous experience of encountering antigens. The understanding of... (Review)
Review
The innate immune system of insects can respond more swiftly and efficiently to pathogens based on previous experience of encountering antigens. The understanding of molecular mechanisms governing immune priming, a form of immune memory in insects, including its transgenerational inheritance, remains elusive. It is still unclear if the enhanced expression of immune genes observed in primed insects can persist and be regulated through changes in chromatin structure via epigenetic modifications of DNA or histones, mirroring observations in mammals. Increasing experimental evidence suggests that epigenetic changes at the level of DNA/RNA methylation and histone acetylation can modulate the activation of insects' immune responses to pathogen exposure. Moreover, transgenerational inheritance of certain epigenetic modifications in model insect hosts can influence the transmission of pre-programmed immune responses to the offspring, leading to the development of evolved resistance. Epigenetic research in model insect hosts is on the brink of significant progress in the mechanistic understanding of chromatin remodeling within innate immunity, particularly the direct relationships between immunological priming and epigenetic alterations. In this review, we discuss the latest discoveries concerning the involvement of DNA methylation and histone acetylation in shaping the development, maintenance, and inheritance of immune memory in insects, culminating in the evolution of resistance against pathogens.
Topics: Animals; Epigenesis, Genetic; Immunologic Memory; Insecta; DNA Methylation; Histones; Immunity, Innate; Chromatin Assembly and Disassembly; Acetylation
PubMed: 38915407
DOI: 10.3389/fimmu.2024.1397521 -
Molecular Neurodegeneration Jun 2024Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury...
BACKGROUND
Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models.
METHODS
We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects.
RESULTS
Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice.
CONCLUSIONS
The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.
Topics: Animals; Tauopathies; tau Proteins; Mice; Acetylation; Humans; Immunotherapy; Disease Models, Animal; Mice, Transgenic; Brain Injuries, Traumatic; Brain Injuries; Brain; Neuroprotective Agents
PubMed: 38915105
DOI: 10.1186/s13024-024-00733-9 -
Journal of the American Heart... Jun 2024A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the...
BACKGROUND
A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population.
METHODS AND RESULTS
The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study). Plasma ceramide and sphingomyelin species carrying long-chain (ie, 16:0) and very-long-chain (ie, 20:0, 22:0, 24:0) saturated fatty acids were measured by sequential liquid chromatography and mass spectroscopy using samples from 2001 to 2003. Participants were followed for 18.8 years (2001-2020). Associations of ceramides and sphingomyelins with mortality were assessed using Cox models. The mean age of participants was 40.8 years. There were 574 deaths during a median 17.4-year follow-up. Ceramides and sphingomyelins carrying fatty acid 16:0 were positively associated with mortality. Ceramides and sphingomyelins carrying longer fatty acids were inversely associated with mortality. Per SD difference in each ceramide and sphingomyelin species, hazard ratios for death were: 1.68 (95% CI, 1.44-1.96) for ceramide-16 (Cer-16), 0.82 (95% CI, 0.71-0.95) for Cer-20, 0.60 (95% CI, 0.51-0.70) for Cer-22, 0.67 (95% CI, 0.56-0.79) for Cer-24, 1.80 (95% CI-1.57, 2.05) for sphingomyelin-16 (SM-16), 0.54 (95% CI, 0.47-0.62) for SM-20, 0.50 (95% CI, 0.44-0.57) for SM-22, and 0.59 (95% CI, 0.52-0.67) for SM-24.
CONCLUSIONS
The direction/magnitude of associations of ceramides and sphingomyelins with mortality differs according to the length of the fatty acid acylated to the backbone sphingoid base.
REGISTRATION
URL: https://www.clinicatrials.gov; Unique identifier: NCT00005134.
PubMed: 38904223
DOI: 10.1161/JAHA.123.032536 -
BMC Genomics Jun 2024Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing...
Multi-omic analysis reveals the effects of interspecific hybridization on the synthesis of seed reserve polymers in a Triticum turgidum ssp. durum × Aegilops sharonensis amphidiploid.
BACKGROUND
Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers.
RESULTS
The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. CONCLUSION: After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.
Topics: Triticum; Aegilops; Seeds; Hybridization, Genetic; Polyploidy; Starch; Transcriptome; Gene Expression Profiling; Gene Expression Regulation, Plant; Proteomics; Multiomics
PubMed: 38902625
DOI: 10.1186/s12864-024-10352-9 -
Molecules (Basel, Switzerland) Jun 2024Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the cytotoxicity of the genotoxic anticancer drug cisplatin, yet the underlying mechanism remains...
Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the cytotoxicity of the genotoxic anticancer drug cisplatin, yet the underlying mechanism remains poorly understood. Herein, we revealed that TSA at a low concentration (1 μM) promoted the cisplatin-induced activation of caspase-3/6, which, in turn, increased the level of cleaved PARP1 and degraded lamin A&C, leading to more cisplatin-induced apoptosis and G2/M phase arrest of A549 cancer cells. Both ICP-MS and ToF-SIMS measurements demonstrated a significant increase in DNA-bound platinum in A549 cells in the presence of TSA, which was attributable to TSA-induced increase in the accessibility of genomic DNA to cisplatin attacking. The global quantitative proteomics results further showed that in the presence of TSA, cisplatin activated INF signaling to upregulate STAT1 and SAMHD1 to increase cisplatin sensitivity and downregulated ICAM1 and CD44 to reduce cell migration, synergistically promoting cisplatin cytotoxicity. Furthermore, in the presence of TSA, cisplatin downregulated TFAM and SLC3A2 to enhance cisplatin-induced ferroptosis, also contributing to the promotion of cisplatin cytotoxicity. Importantly, our posttranslational modification data indicated that acetylation at H4K8 played a dominant role in promoting cisplatin cytotoxicity. These findings provide novel insights into better understanding the principle of combining chemotherapy of genotoxic drugs and HDAC inhibitors for the treatment of cancers.
Topics: Cisplatin; Humans; Apoptosis; Hydroxamic Acids; Antineoplastic Agents; A549 Cells; Histone Deacetylase Inhibitors; Cell Line, Tumor; Acetylation; Drug Synergism
PubMed: 38893499
DOI: 10.3390/molecules29112623 -
Molecules (Basel, Switzerland) May 2024Cabernet Sauvignon from the California Paso Robles AVA was processed with a contrasting array of cap management frequencies, consisting of punch-down (PD) frequencies...
Cabernet Sauvignon from the California Paso Robles AVA was processed with a contrasting array of cap management frequencies, consisting of punch-down (PD) frequencies (0, 1, 2, and 3 PD/day) over two vintages, one of which the fruit was harvested at two contrasting maturity levels. Wines followed with up to 3 years of bottle aging for basic and phenolic chemistry, and the wines of the second harvest of 2020 were submitted to sensory analysis. There were almost non-existent effects due to the frequency of punch downs on parameters such as ethanol, pH, titratable acidity, lactic acid, and glucose + fructose. In 2019, the chromatic differences between different PD regimes were subtle, and minor effects of the punch-down frequency were observed for tannins and total phenolics. During the early stages of alcoholic fermentation, higher levels of all anthocyanin classes were observed in 1 PD wines and the lowest levels in 0 PD wines. The anthocyanin content of the wines of the first harvest (unripe) was 27% higher than that of the wines of the second harvest (ripe), but these differences disappeared after 3 years of bottle aging irrespective of the vintage and harvest date. Acylated anthocyanins were preferentially lost during aging, especially in 2019 wines and, to a lesser extent, in 2020 wines. In 2020, the polymeric pigment content of the wines of the second harvest was higher than in the wines of the first harvest, with 3 PD wines showing higher polymeric pigments and yellow hues than 0 and 2 PD wines after 3 years of bottle aging. Sensory analysis of the second harvest of the 2020 wines showed that the wines of all four PD regimes were perceived as drying, signifying they were perceived as equally astringent, which is consistent with comparable tannin levels on said wines. The perception of bitterness increased with the frequency of punch downs; thus, 3 PD wines showed the highest bitterness perception. It was concluded that in sufficiently warm fermentations and small volumes, phenolic extraction occurs regardless of fruit maturity and under conditions of minimum mixing.
Topics: Wine; Phenols; Vitis; Anthocyanins; California; Taste; Fruit; Humans; Fermentation
PubMed: 38893385
DOI: 10.3390/molecules29112509 -
Molecules (Basel, Switzerland) May 2024A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible...
A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.
PubMed: 38893325
DOI: 10.3390/molecules29112449 -
International Journal of Molecular... May 2024Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism...
Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin's anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.
Topics: Animals; Zebrafish; Melanins; Molecular Docking Simulation; Phosphorylation; MAP Kinase Signaling System; Signal Transduction; Cyclic AMP Response Element-Binding Protein; Monophenol Monooxygenase; Microphthalmia-Associated Transcription Factor; Melanocytes
PubMed: 38892131
DOI: 10.3390/ijms25115939 -
Foods (Basel, Switzerland) May 2024The study investigates the structural and chemical properties of brown rice flour (WRF), black rice flour (BRF) and their mixtures in ratios of 25%, 50% and 75% to...
The study investigates the structural and chemical properties of brown rice flour (WRF), black rice flour (BRF) and their mixtures in ratios of 25%, 50% and 75% to provide reference information for the gluten-free bakery industry. BRF contains higher concentrations of proteins, lipids, total minerals, crude fiber, total polyphenols, proanthocyanidins and flavonoids than WRF. A higher amylose content in BRF than in WRF resulted in flour mixtures with slower starch digestion and a lower glycemic response depending on the BRF ratio added. Differences in the chemical composition of WRF and BRF led to improved composition of the flour mixtures depending on the BRF ratio. The presence of anthocyanidins and phenolic acids in higher concentrations in the BRF resulted in a red-blue color shift within the flour mixtures. The deconvoluted FTIR spectra showed a higher proportion of α-helixes in the amide I band of BRF proteins, indicating their tighter folding. An analysis of the FTIR spectra revealed a more compact starch structure in BRF than in WRF. By processing reflection spectra, nine optically active compound groups were distinguished in rice flour, the proportion in BRF being 83.02% higher than in WRF. Due to co-pigmentation, the bathochromic shift to higher wavelengths was expressed by the proanthocyanins and phenolic acids associated with the wavelengths 380 nm to 590 nm and at 695 nm. Anthocyanins, protein-tannin complexes, methylated anthocyanins and acylated anthocyanins, associated with wavelengths 619, 644 and 668 nm, exhibited a hypsochromic effect by shifting the wavelengths to lower values. This research represents a first step in the development of rice-based products with increased nutritional value and a lower glycemic index.
PubMed: 38890821
DOI: 10.3390/foods13111592 -
Scientific Reports Jun 2024The derivation of polysaccharide has an important impact on its properties. The preparation process of phosphorylated-shaddock skin polysaccharides (SSP) and...
The derivation of polysaccharide has an important impact on its properties. The preparation process of phosphorylated-shaddock skin polysaccharides (SSP) and acetylated-SSP was optimized by the response surface method. The constructed model was accurate and reliable in predicting the substitution of acetylated-SSP and the phosphate content of phosphorylated-SSP. This method was simple and easy to operate, which provided a basis for the preparation of a large number of derivatives.
Topics: Polysaccharides; Skin; Animals; Phosphorylation; Acetylation
PubMed: 38890435
DOI: 10.1038/s41598-024-63851-w