Category Archives: RESEARCH ARTICLE

Sodium Danshensu ameliorates cerebral ischemia/reperfusion injury by inhibiting CLIC4/NLRP3 inflammasome‐mediated endothelial cell pyroptosis

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Sodium Danshensu ameliorates cerebral ischemia/reperfusion injury by inhibiting CLIC4/NLRP3 inflammasome-mediated endothelial cell pyroptosis

Mechanism of SDSS in inhibiting endothelial cell pyroptosis. In the priming step, NLRP3, pro-Caspase-1, GSDMD-full, pro-IL-1β, and pro-IL-18 were up-regulated. Furthermore, the translocation of CLIC4 from cytoplasm to the membrane induced chloride outflow, resulting in the assembly of NLRP3, ASC and Pro-Caspase-1 into a platform (activation step). By binding CLIC4 and blocking its membrane localization, SDSS inhibited chloride outflow, thus inhibiting the activation of NLRP3 inflammasome and then the cleavage of pro-Caspase-1 into Caspase-1. This inhibited pyroptosis along with the release of IL-1β and IL-18, resulting from Caspase-1-dependent GSDMD-N cleavage.


Abstract

Endothelial pyroptosis promotes cerebral ischemia/reperfusion injury (CIRI). Sodium Danshensu (SDSS) has been shown to attenuate CIRI and have anti-inflammatory properties in endothelial cells. However, the mechanism and effect of SDSS on alleviating endothelial pyroptosis after CIRI remains poorly understood. Thus, we aimed to investigate the efficacy and mechanism of SDSS in reducing endothelial pyroptosis. It has been shown that SDSS administration inhibited NLRP3 inflammasome-mediated pyroptosis. As demonstrated by protein microarrays, molecular docking, CETSA and ITDRFCETSA, SDSS bound strongly to CLIC4. Furthermore, SDSS can decrease its expression and inhibit its translocation. Its effectiveness was lowered by CLIC4 overexpression but not by knockdown. Overall The beneficial effect of SDSS against CIRI in this study can be ascribed to blocking endothelial pyroptosis by binding to CLIC4 and then inhibiting chloride efflux-dependent NLRP3 inflammasome activation.

Species‐level drivers of avian centrality within seed‐dispersal networks across different levels of organisation

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Species-level drivers of avian centrality within seed-dispersal networks across different levels of organisation

In bird–plant seed-dispersal networks, range size drives species centrality at the global meta-network level, whereas body size is more important at the local network level. Bird ecosystem functions at the global scale are determined by species' capacity to occupy various habitats and interact with a large set of plant species. Species traits: E, evolutionary; G, geographical; M, morphological.


Abstract

Bird–plant seed-dispersal networks are structural components of ecosystems. The role of bird species in seed-dispersal networks (from less [peripheral] to more connected [central]), determines the interaction patterns and their ecosystem services. These roles may be driven by morphological and functional traits as well as evolutionary, geographical and environmental properties acting at different spatial extents. It is still unknown if such drivers are equally important in determining species centrality at different network levels, from individual local networks to the global meta-network representing interactions across all local networks. Using 308 networks covering five continents and 11 biogeographical regions, we show that at the global meta-network level species' range size was the most important driver of species centrality, with more central species having larger range sizes, which would facilitate the interaction with a higher number of plants and thus the maintenance of seed-dispersal interactions. At the local network level, body mass was the only driver with a significant effect, implying that local factors related to resource availability are more important at this level of network organisation than those related to broad spatial factors such as range sizes. This could also be related to the mismatch between species-level traits, which do not consider intraspecific variation, and the local networks that can depend on such variation. Taken together, our results show that the drivers determining species centrality are relative to the levels of network organisation, suggesting that prediction of species functional roles in seed-dispersal interactions requires combined local and global approaches.

Resumen

Las redes de dispersión de semillas entre aves y plantas son componentes estructurales de los ecosistemas. El rol de las especies de aves en estas redes de dispersión de semillas (de menos [periféricas] a más conectadas [centrales]), determina los patrones de interacción y sus servicios ecosistémicos. Estos roles pueden ser impulsados por rasgos morfológicos y funcionales, propiedades evolutivas, geográficas y ambientales que actúan en diferentes extensiones espaciales. Todavía se desconoce si dichos impulsores son igualmente importantes para determinar la centralidad de las especies en diferentes niveles de red, desde redes locales individuales hasta la meta-red global que representa todas las interacciones en las redes locales. Usando 308 redes abarcando cinco continentes y once regiones biogeográficas, mostramos que a nivel de meta-red global, el tamaño de la distribución geográfica de las especies fue el factor más determinante de la centralidad de las especies, con especies más centrales siendo aquellas que tienen distribuciones más grandes, lo que les facilitaría la interacción con un mayor número de plantas y por lo tanto el mantenimiento de las interacciones de dispersión de semillas. A nivel de las redes locales, la masa corporal fue el único impulsor con un efecto significativo, lo que implica que los factores locales relacionados con la disponibilidad de recursos son más importantes en este nivel de organización que los relacionados con factores espaciales amplios, como el tamaño de las distribuciones. Esto también podría estar relacionado con el desajuste entre los rasgos a nivel de especie, que no consideran la variación intraespecífica, y las redes locales que pueden depender de dicha variación. En conjunto, nuestros resultados muestran que los impulsores que determinan la centralidad de las especies en las redes de interacción son relativos a los niveles de organización de la red, lo que sugiere que la predicción de los roles funcionales de las especies en las interacciones de dispersión de semillas requiere enfoques locales y globales combinados.

P38α contributes to TNF‐α‐induced IL‐8 production in human gingival cells

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P38α contributes to TNF-α-induced IL-8 production in human gingival cells

When phosphorylated at threonine 180 and tyrosine 182, p38α contributes to the induction of IL-8 by TNF-α in Ca9-22 cells. TNF-α-induced phosphorylation translocates NF-κB into the nucleus and then increases both IL-8 mRNA expression and secretion. Thus, p38α plays an important role in TNF-α-induced IL-8 production, providing a potential therapeutic target to prevent and treat periodontal disease.


Abstract

Tumor necrosis factor-alpha (TNF-α) is a major inflammatory cytokine that induces interleukin (IL)-8 production. Although some studies have reported the involvement of the p38 MAPK signaling pathway in TNF-α-induced IL-8 production, its specific regulatory mechanisms in gingival epithelial cells (GECs) are still poorly understood. In the present study, Ca9-22 cells were used as representative GECs to investigate the effect of p38 signaling on TNF-α-induced IL-8 production. We found that TNF-α enhanced IL-8 production in Ca9-22 cells by activating the p38 signaling pathway, and one of its isoforms, p38α, played a key role. P38α deletion markedly inhibited TNF-α-induced IL-8 expression in Ca9-22 cells, while p38α gene rescue could reverse this effect. Further studies revealed that TNF-α-induced IL-8 production was markedly reduced when the threonine 180 and tyrosine 182 p38α phosphorylation sites were targeted for mutagenesis to alanine and phenylalanine, respectively, suggesting their critical role in the process. In conclusion, p38α plays an important role in TNF-α-induced IL-8 production, providing a potential therapeutic target to prevent and treat periodontal disease.

Evaluating the performance of genomic prediction accounting for effects of single nucleotide polymorphism markers in reproductive traits of Japanese Black cattle

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Abstract

We examined the prediction accuracies of genomic best linear unbiased prediction (GBLUP), various weighted GBLUP according to the degrees of marker effects (WGBLUP) and machine learning (ML) methods, and compared them with traditional BLUP for age at first calving (AFC), calving difficulty (CD), and gestation length in Japanese Black cattle. For WGBLUP, firstly, BayesC and FarmCPU were used to estimate marker effects. Then, we constructed three weighted genomic relationship matrices from information of estimated marker effects in the first step: absolute value of the estimated marker-effect WGBLUP, estimated marker-variance WGBLUP, and genomic-feature WGBLUP. For ML, we applied Gaussian kernel, random forest, extreme gradient boost, and support vector regression. We collected a total of 2583 animals having both phenotypic records and genotypes with 30,105 markers and 16,406 pedigree records. For AFC, prediction accuracies of WGBLUP methods using FarmCPU exceeded BLUP by 25.7%–39.5%. For CD, estimated marker-variance WGBLUP using BayesC achieved the highest prediction accuracy. Among ML methods, extreme gradient boost, support vector regression, and Gaussian kernel increased prediction accuracies by 28.4%, 19.0%, and 36.4% for AFC, CD, and gestation length compared with BLUP, respectively. Thus, prediction performance could be improved using suitable WGBLUP and ML methods according to target reproductive traits for the population used.

The m6A modification of Il17a in CD4+ T cells promotes inflammation in psoriasis

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The m6A modification of Il17a in CD4+ T cells promotes inflammation in psoriasis

Molecular mechanism of m6A in CD4+ T cells in psoriasis.


Abstract

Psoriasis is a chronic inflammatory skin disorder. The mechanism of psoriasis pathogenesis is not entirely clear. Here, we reported that the level of the N6-methyladenosine (m6A) modification was increased in psoriatic CD4+ T cells compared with healthy controls. In the psoriasis mouse model, depletion of the RNA demethylase, Alkbh5, from CD4+ T cells promoted the psoriasis-like phenotype and inflammation. Intriguingly, this phenotype and inflammation were alleviated by the ablation of the m6A methyltransferase Mettl3 in CD4+ T cells. Mechanistically, we found that the m6A modification of IL17A mRNA increased the expression of IL-17A (an important pro-inflammatory factor in psoriasis) and promoted psoriasis. Thus, our study provided evidence that the m6A modification of IL17A in CD4+ T cells regulates inflammation in psoriasis.

Label‐free proteomic analysis reveals an estrous cycle transition between the follicular phase and the luteal phase in yak ovary

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Abstract

In order to further study the physiological mechanism about yak reproduction for the improvement of its fertility, differentially expressed proteins (DEGs) of the ovary were screened during the follicular and luteal phases of yak based on label-free quantitative proteomics. The main research results were as follows: it discovered 2867 proteins during the follicular phase and 2180 proteins during the luteal phase, among which there were 2011 proteins of expression during both phases, 856 during the follicular phase, and 169 during the luteal phase. According to the bioinformatics and Gene Ontology analysis, the screened differentially expressed proteins were mostly located in the cell membrane and extracellular region and primarily acted on the activity of laminin. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the main involvement of differentially expressed proteins included steroid biosynthesis, chemokine signaling pathway, protein processing in the endoplasmic reticulum, glycerol phospholipid metabolism, carbon metabolism, PI3K-Akt signaling pathways, PPAR signaling pathways, nucleotide oligomerization domain (NOD) receptor signaling pathways, and purine metabolic pathways. Screened proteins related to reproductive function, so as to lay a theoretical foundation for the in-depth study of the regulation mechanism of yak reproduction and improve its fertility.

Heat enhances the inhibitory effect of lipopolysaccharide on duck granulosa cell proliferation and steroid biosynthesis in vitro

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Abstract

Lipopolysaccharide (LPS) reduces the reproductive performance of laying ducks, especially during the hot summer months. To study the underlying mechanisms, we investigated the effects of different LPS concentrations and heat on duck granulosa cell (GC) proliferation and steroid biosynthesis in vitro. We investigated GC proliferation, secretion, and activation of the MAPK pathway. The cell cycle results showed that LPS treatment alone did not significantly affect cell proliferation, whereas the mRNA expression levels of IGF2, IGFBP2, and CyclinD1 were downregulated and p27kip1 was significantly upregulated after 2000 ng/mL LPS treatment when compared to untreated cells. In steroid hormone synthesis, although LPS increased the expression of most steroid biosynthesis genes, it inhibited the expression of CYP11A1 at high LPS concentrations. High temperatures enhanced the inhibitory effect of LPS on the expression of proliferation-promoting genes. Heat significantly reduced CYP11A1 and CYP19A1 expression. In addition, the phosphorylation of P38 was significantly upregulated by high temperatures combined with LPS, whereas the phosphorylation of ERK1/2 and JNK was downregulated. The relative protein expression of Bax/BCL-2 was upregulated at high temperatures in combination with LPS. Heat treatment enhanced the inhibitory effects of LPS on the proliferation and hormone biosynthesis of duck GCs in vitro.

A novel lncRNA LOC105613571 binding with BDNF in pituitary promotes gonadotropin secretion by AKT/ERK‐mTOR pathway in sheep associated with prolificacy

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A novel lncRNA LOC105613571 binding with BDNF in pituitary promotes gonadotropin secretion by AKT/ERK-mTOR pathway in sheep associated with prolificacy

Candidate lncRNA LOC105613571 targeted BDNF via trans-regulated relationships was characterized by pituitary transcriptome from Hu sheep with high and low fecundity. GnRH stimulation increased BDNF and lncRNA LOC105613571 expression in pituitary cells. BDNF-binding lncRNA LOC105613571 promotes pituitary gonadotropin secretion by activating AKT/ERK-mTOR pathway in pituitary cells.


Abstract

The pituitary is a vital endocrine organ for synthesis and secretion of gonadotropic hormones (FSH and LH), and the gonadotropin showed fluctuations in animals with different fecundity. Long non-coding RNAs (lncRNAs) have been identified as regulatory factors for the reproductive process. However, the profiles of lncRNAs and their roles involved in sheep fecundity remains unclear. In this study, we performed RNA-sequencing for the sheep pituitary gland associated with different fecundity, and identified a novel candidate lncRNA LOC105613571 targeting BDNF related to gonadotropin secretion. Our results showed that expression of lncRNA LOC105613571 and BDNF could be significantly upregulated by GnRH stimulation in sheep pituitary cells in vitro. Notably, either lncRNA LOC105613571 or BDNF silencing inhibited cell proliferation while promoted cell apoptosis. Moreover, lncRNA LOC105613571 knockdown could also downregulate gonadotropin secretion via inactivation AKT, ERK and mTOR pathway. In addition, co-treatment with GnRH stimulation and lncRNA LOC105613571 or BDNF knockdown showed the opposite effect on sheep pituitary cells in vitro. In summary, BDNF-binding lncRNA LOC105613571 in sheep regulates pituitary cell proliferation and gonadotropin secretion via the AKT/ERK-mTOR pathway, providing new ideas for the molecular mechanisms of pituitary functions.

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS‐induced apoptosis

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Abstract

Berberine exerts many beneficial effects on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (BEECs). Recently, we also found that berberine shows significant antiapoptotic and autophagy-promoting activities, but the underlying mechanism has not been elucidated. This research explored the association between the antiapoptotic and autophagy-promoting activities of berberine in LPS-treated BEECs. BEECs were first preconditioned with an inhibitor of autophagic flux (chloroquine [CQ]) for 1 h, treated with berberine for 2 h, and then incubated with LPS for 3 h. Cell apoptosis was assessed by flow cytometry, and autophagy activities were assessed by immunoblot analysis of LC3II and p62. The results indicated that the antiapoptotic activity of berberine was notably inhibited in LPS-treated BEECs after preconditioning with CQ for 1 h. Furthermore, to determine whether berberine promoted autophagy by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, we assessed autophagy in LPS-treated BEECs after preconditioning with a signaling pathway inhibitor of Nrf2 (ML385). The results indicated that the enhanced autophagy activity induced by berberine was partially reversed in LPS-treated BEECs after the Nrf2 signaling pathway was disturbed by ML385. In conclusion, berberine enhances autophagic flux to allow resistance to LPS-induced apoptosis by activating the Nrf2 signaling pathway in BEECs. The present study may provide new insight into the antiapoptotic mechanism of berberine in LPS-induced BEECs.

Effects of a low‐protein diet supplemented with essential amino acids on egg production performance and environmental gas emissions from layer‐manure composting in laying hens in the later laying period

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Abstract

We fed 330–545 day-old laying hens (later laying period) a low-protein diet supplemented with essential amino acids (LPS) and composted their manure. We then investigated the laying performance of the hens, the nitrogen balance and emission of nitrous oxide (N2O), methane (CH4), and ammonia (NH3) from the composting, and several characteristics of the finished compost. There were no significant differences in the egg-laying rate, egg mass, egg weight, proximate compositions in egg yolk and egg white, or feed intake between the laying hens fed a Control diet (Cont) and those fed the LPS diet. However, the LPS-fed hens had lower excreta levels and nitrogen excretion. In addition, the environmental gas emissions per layer from composting of the manure from the LPS-fed laying hens were decreased by 9.7% for N2O, 40.9% for CH4, and 24.8% for NH3 compared to the Cont-fed laying hens. The concentrations of total nitrogen in the finished compost were similar between the LPS-fed and Cont-fed laying hens. In a vegetable-growth test, the weights of komatsuna plants grown with compost from LPS-fed and Cont-fed hens were also not significantly different. Feeding an LPS diet to 330–545 day-old laying hens was suggested to reduce environmental gas emissions from manure composting without affecting the egg production performance.