Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells
Objective To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells. Methods The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis. Results The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs. Conclusion JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.
Zheng et al. (2024) Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells. PeerJ 12:e17035 https://doi.org/10.7717/peerj.17035
AMMI and GGE biplot analysis for genotype × environment interactions affecting the yield and quality characteristics of sugar beet
Sugar beet, an important sugar crop, contributes significantly to the world’s sugar production. However, genotype–environment interactions (GEI) often affect the quality characteristics of sugar beet. Hence, understanding the effects of GEI on sugar beet quality can aid in identifying high-quality genotypes that can adapt to different environments. Traditional variance analysis can only be used to examine the yield of a variety and not its specific adaptability to specific conditions. Therefore, more comprehensive analytical methods are required to evaluate the characteristics of the variety under specific environments. Additive main effects and multiplicative interaction (AMMI) and genotype main effect and genotype × environment interaction (GGE) biplot models can be employed to comprehensively evaluate different varieties and address the drawbacks associated with a single evaluation method. Moreover, these models also allow us to explore new varieties more objectively and comprehensively. In this study, the adaptability and stability of 16 sugar beet varieties, in terms of yield and sugar content, were evaluated using AMMI and GGE biplot analysis in seven pilot projects undertaken in 2022. In the assessment of a small but significant proportion of the total GEI variance for the two qualitative traits (yield and sugar content), 80.58% of the variance was explained by the cumulative contribution of IPC1, IPC2, and IPC3. AMMI and GGE biplots clearly highlighted that KWS4207 (G3) exhibited high and stable quality. They also demonstrated that the experiments in Jalaid Banner (Inner Mongolia) (E7) were the most representative. Together, the results suggested that the comprehensive application of AMMI and GGE biplot analysis allowed for a more comprehensive, scientific, and effective evaluation of sugar beet varieties across different regions. The findings offer a theoretical basis for sugar beet breeding and could guide the rational design of experiments for testing new varieties of sugar beet.
Dang et al. (2024) AMMI and GGE biplot analysis for genotype × environment interactions affecting the yield and quality characteristics of sugar beet. PeerJ 12:e16882 https://doi.org/10.7717/peerj.16882
The association between urbanization and adolescent depression in China
Background With the rapid urbanization in many countries, more attention is being paid to the relationship between urbanization and mental health, especially depression. However, in countries with rapid urbanization, few empirical studies exist on the relationship between urbanization and adolescent depression. Methods Nationally representative survey data from the China Family Panel Studies in 2012, 2016 and 2018 were used. Data of 1,588 adolescents were obtained from 25 provinces. Depression was measured using the Center for Epidemiology Studies of Depression 20-item score. The urbanization rate was obtained from the National Bureau of Statistics of China. The generalized estimating equation was used to estimate the statistical relationship. Results The participants’ mean age at baseline was 15 years, and 51.2% (813/1,588) of participants were male. After adjusting for all covariates (gender, age, ethnicity, level of education, marital status, urban/rural areas, body mass index, self-rated health, academic pressure, smoking, drinking and exercise), the rate of urbanization was monotonically and negatively associated with adolescent depression (odds ratio 0.34, 95% CI [0.14–0.79]). Compared with female adolescents, male adolescents had a lower risk of depression (odds ratio 0.80, 95% CI [0.67–0.97]). Conclusion In the context of China, urbanization has a positive effect on the mental health of adolescents. Female adolescents are more likely to experience depression than male adolescents.
Pan et al. (2024) The association between urbanization and adolescent depression in China. PeerJ 12:e16888 https://doi.org/10.7717/peerj.16888
Exploratory study to characterise the individual types of health literacy and beliefs and their associations with infection prevention behaviours amid the COVID-19 pandemic in Japan: a longitudinal study
Background During a global infectious disease pandemic such as the coronavirus disease 2019 (COVID-19), individuals’ infection prevention/risk-taking behaviours are likely to differ depending on their health literacy and beliefs regarding the disease. To effectively promote infection prevention behaviours, it is necessary to enable information dissemination and risk communication that consider individuals’ health literacy and beliefs. In this study, we exploratorily characterised segments based on individual health literacy and beliefs regarding COVID-19 among the Japanese during the early stage of the COVID-19 pandemic, and investigated whether infection prevention/risk-taking behaviours and fear of COVID-19 differed among these segments. Methods In this study, we conducted two web-based longitudinal surveys in Japan (PHASE 1, 1–30 November 2020, 6,000 participants; PHASE 2, 1–31 December 2020, 3,800 participants). We characterised segments of the target population using cluster analysis on health literacy and beliefs regarding COVID-19 obtained in PHASE 1. We further investigated the associations between the clusters and infection prevention/risk-taking behaviours and fear of COVID-19, obtained from PHASE 2. Results Five clusters were identified: ‘Calm/hoax denial’, ‘Hoax affinity/threat denial’, ‘Minority/indifference’, ‘Over vigilance’, and ‘Optimism’. There were significant differences in infection prevention/risk-taking behaviours and fear of COVID-19 among the five clusters. The belief in susceptibility to infection, rather than affinity for hoaxes and conspiracy theories, was coherently associated with infection prevention/risk-taking behaviours and fear of infection across clusters. This study provides foundational knowledge for creating segment-specific public messages and developing interactive risk communication to encourage infection prevention behaviours.
Yagihashi et al. (2024) Exploratory study to characterise the individual types of health literacy and beliefs and their associations with infection prevention behaviours amid the COVID-19 pandemic in Japan: a longitudinal study. PeerJ 12:e16905 https://doi.org/10.7717/peerj.16905
Color components determination and full-length comparative transcriptomic analyses reveal the potential mechanism of carotenoid synthesis during Paphiopedilum armeniacum flowering
Background Paphiopedilum armeniacum (P. armeniacum), an ornamental plant native to China, is known for its distinctive yellow blossoms. However, the mechanisms underlying P. armeniacum flower coloration remain unclear. Methods We selected P. armeniacum samples from different flowering stages and conducted rigorous physicochemical analyses. The specimens were differentiated based on their chemical properties, specifically their solubilities in polar solvents. This key step enabled us to identify the main metabolite of flower color development of P. armeniacum, and to complete the identification by High-performance liquid chromatography (HPLC) based on the results. Additionally, we employed a combined approach, integrating both third-generation full-length transcriptome sequencing and second-generation high-throughput transcriptome sequencing, to comprehensively explore the molecular components involved. Results We combined physical and chemical analysis with transcriptome sequencing to reveal that carotenoid is the main pigment of P. armeniacum flower color. Extraction colorimetric method and HPLC were used to explore the characteristics of carotenoid accumulation during flowering. We identified 28 differentially expressed carotenoid biosynthesis genes throughout the flowering process, validated their expression through fluorescence quantification, and discovered 19 potential positive regulators involved in carotenoid synthesis. Among these candidates, three RCP2 genes showed a strong potential for governing the PDS and ZDS gene families. In summary, our study elucidates the fundamental mechanisms governing carotenoid synthesis during P. armeniacum flowering, enhancing our understanding of this process and providing a foundation for future research on the molecular mechanisms driving P. armeniacum flowering.
Bai et al. (2024) Color components determination and full-length comparative transcriptomic analyses reveal the potential mechanism of carotenoid synthesis during Paphiopedilum armeniacum flowering. PeerJ 12:e16914 https://doi.org/10.7717/peerj.16914
Hypoxic bone marrow mesenchymal stem cell exosomes promote angiogenesis and enhance endometrial injury repair through the miR-424-5p-mediated DLL4/Notch signaling pathway
Background Currently, bone marrow mesenchymal stem cells (BMSCs) have been reported to promote endometrial regeneration in rat models of mechanically injury-induced uterine adhesions (IUAs), but the therapeutic effects and mechanisms of hypoxic BMSC-derived exosomes on IUAs have not been elucidated. Objective To investigate the potential mechanism by which the BMSCS-derived exosomal miR-424-5p regulates IUA angiogenesis through the DLL4/Notch signaling pathway under hypoxic conditions and promotes endometrial injury repair. Methods The morphology of the exosomes was observed via transmission electron microscopy, and the expression of exosome markers (CD9, CD63, CD81, and HSP70) was detected via flow cytometry and Western blotting. The expression of angiogenesis-related genes (Ang1, Flk1, Vash1, and TSP1) was detected via RT‒qPCR, and the expression of DLL4/Notch signaling pathway-related proteins (DLL4, Notch1, and Notch2) was detected via Western blotting. Cell proliferation was detected by a CCK-8 assay, and angiogenesis was assessed via an angiogenesis assay. The expression of CD3 was detected by immunofluorescence. The endometrial lesions of IUA rats were observed via HE staining, and the expression of CD3 and VEGFA was detected via immunohistochemistry. Results Compared with those in exosomes from normoxic conditions, miR-424-5p was more highly expressed in the exosomes from hypoxic BMSCs. Compared with those in normoxic BMSC-derived exosomes, the proliferation and angiogenesis of HUVECs were significantly enhanced after treatment with hypoxic BMSC-derived exosomes, and these effects were weakened after inhibition of miR-424-5p. miR-424-5p can target and negatively regulate the expression of DLL4, promote the expression of the proangiogenic genes Ang1 and Flk1, and inhibit the expression of the antiangiogenic genes Vash1 and TSP1. The effect of miR-424-5p can be reversed by overexpression of DLL4. In IUA rats, treatment with hypoxic BMSC exosomes and the miR-424-5p mimic promoted angiogenesis and improved endometrial damage. Conclusion The hypoxic BMSC-derived exosomal miR-424-5p promoted angiogenesis and improved endometrial injury repair by regulating the DLL4/Notch signaling pathway, which provides a new idea for the treatment of IUAs.
Xiong et al. (2024) Hypoxic bone marrow mesenchymal stem cell exosomes promote angiogenesis and enhance endometrial injury repair through the miR-424-5p-mediated DLL4/Notch signaling pathway. PeerJ 12:e16953 https://doi.org/10.7717/peerj.16953
Beneficial endophytic fungi improve the yield and quality of Salvia miltiorrhiza by performing different ecological functions
Background Endophytic fungi can enhance the growth and synthesis of secondary metabolites in medicinal plants. Salvia miltiorrhiza Bunge is frequently employed for treating cardiovascular and cerebrovascular ailments, with the primary bioactive components being salvianolic acid and tanshinone. However, their levels in cultivated S. miltiorrhiza are inferior to that of the wild herbs, so the production of high-quality medicinal herbs is sharply declining. Consequently, the utilization of beneficial endophytic fungi to improve the yield and quality of S. miltiorrhiza holds great significance for the cultivation of medicinal plants. Methods In this study, nine non-pathogenic, endophytic fungal strains were introduced into sterile S. miltiorrhiza seedlings and cultivated both in vitro and in situ (the greenhouse). The effects of these strains on the growth indices, C and N metabolism, antioxidant activity, photosynthesis, and content of bioactive ingredients in S. miltiorrhiza were then evaluated. Results The results showed that the different genera, species, or strains of endophytic fungi regulated the growth and metabolism of S. miltiorrhiza in unique ways. These endophytic fungi primarily exerted their growth-promoting effects by increasing the net photosynthetic rate, intercellular CO2 concentration, and the activities of sucrose synthase, sucrose phosphate synthase, nitrate reductase, and glutamine synthetase. They also enhanced the adaptability and resistance to environmental stresses by improving the synthesis of osmoregulatory compounds and the activity of antioxidant enzymes. However, their regulatory effects on the growth and development of S. miltiorrhiza were affected by environmental changes. Moreover, the strains that significantly promoted the synthesis and accumulation of phenolic acids inhibited the accumulation of tanshinones components, and vice versa. The endophytic fungal strains Penicillium meloforme DS8, Berkeleyomyces basicola DS10, and Acremonium sclerotigenum DS12 enhanced the bioaccumulation of tanshinones. Fusarium solani DS16 elevated the rosmarinic acid content and yields in S. miltiorrhiza. The strain Penicillium javanicum DS5 improved the contents of dihydrotanshinone, salvianolic acid B, and rosmarinic acid. The strains P. meloforme DS8 and B. basicola DS10 improved resistance. Conclusion Various endophytic fungi affected the quality and yield of S. miltiorrhiza by regulating different physiological and metabolic pathways. This study also provides a novel and effective method to maximize the effects of beneficial endophytic fungi by selecting specific strains to design microbial communities based on the different ecological functions of endophytic fungi under varying environments and for specific production goals.
Li et al. (2024) Beneficial endophytic fungi improve the yield and quality of Salvia miltiorrhiza by performing different ecological functions. PeerJ 12:e16959 https://doi.org/10.7717/peerj.16959
miR-138-5p ameliorates intestinal barrier disruption caused by acute superior mesenteric vein thrombosis injury by inhibiting the NLRP3/HMGB1 axis
Background Acute superior mesenteric venous thrombosis (ASMVT) decreases junction-associated protein expression and intestinal epithelial cell numbers, leading to intestinal epithelial barrier disruption. Pyroptosis has also recently been found to be one of the important causes of mucosal barrier defects. However, the role and mechanism of pyroptosis in ASMVT are not fully understood. Methods Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). Gene expression levels were determined by RNA extraction and reverse transcription-quantitative PCR (RT–qPCR). Western blot and immunofluorescence staining analysis were used to analyze protein expression. H&E staining was used to observe the intestinal tissue structure. Cell Counting Kit-8 (CCK-8) and fluorescein isothiocyanate/propidine iodide (FITC/PI) were used to detect cell viability and apoptosis, respectively. Dual-luciferase reporter assays prove that miR-138-5p targets NLRP3. Results miR-138-5p expression was downregulated in ASMVT-induced intestinal tissues. Inhibition of miR-138-5p promoted NLRP3-related pyroptosis and destroyed tight junctions between IEC-6 cells, ameliorating ASMVT injury. miR-138-5p targeted to downregulate NLRP3. Knockdown of NLRP3 reversed the inhibition of proliferation, apoptosis, and pyroptosis and the decrease in tight junction proteins caused by suppression of miR-138-5p; however, this effect was later inhibited by overexpressing HMGB1. miR-138-5p inhibited pyroptosis, promoted intestinal epithelial tight junctions and alleviated ASMVT injury-induced intestinal barrier disruption via the NLRP3/HMGB1 axis.
Li et al. (2024) miR-138-5p ameliorates intestinal barrier disruption caused by acute superior mesenteric vein thrombosis injury by inhibiting the NLRP3/HMGB1 axis. PeerJ 12:e16692 https://doi.org/10.7717/peerj.16692
Identification of quantitative trait loci (QTLs) regulating leaf SPAD value and trichome density in mungbean (Vigna radiata L.) using genotyping-by-sequencing (GBS) approach
Quantitative trait loci (QTL) mapping is used for the precise localization of genomic regions regulating various traits in plants. Two major QTLs regulating Soil Plant Analysis Development (SPAD) value (qSPAD-7-1) and trichome density (qTric-7-2) in mungbean were identified using recombinant inbred line (RIL) populations (PMR-1×Pusa Baisakhi) on chromosome 7. Functional analysis of QTL region identified 35 candidate genes for SPAD value (16 No) and trichome (19 No) traits. The candidate genes regulating trichome density on the dorsal leaf surface of the mungbean include VRADI07G24840, VRADI07G17780, and VRADI07G15650, which encodes for ZFP6, TFs bHLH DNA-binding superfamily protein, and MYB102, respectively. Also, candidate genes having vital roles in chlorophyll biosynthesis are VRADIO7G29860, VRADIO7G29450, and VRADIO7G28520, which encodes for s-adenosyl-L-methionine, FTSHI1 protein, and CRS2-associated factor, respectively. The findings unfolded the opportunity for the development of customized genotypes having high SPAD value and high trichome density having a possible role in yield and mungbean yellow vein mosaic India virus (MYMIV) resistance in mungbean.
Kumari et al. (2024) Identification of quantitative trait loci (QTLs) regulating leaf SPAD value and trichome density in mungbean (Vigna radiata L.) using genotyping-by-sequencing (GBS) approach. PeerJ 12:e16722 https://doi.org/10.7717/peerj.16722
Proteomic study on nintedanib in gastric cancer cells
Background Gastric cancer is a very common gastrointestinal tumor with a high mortality rate. Nintedanib has been shown to significantly reduce tumor cell proliferation and increase apoptosis in gastric cancer cells in vitro. However, its systemic action mechanism on gastric cancer cells remains unclear. A high-throughput proteomic approach should help identify the potential mechanisms and targets of nintedanib on gastric cancer cells. Methods The effects of nintedanib on the biological behavior of gastric cancer cells were evaluated. A cytotoxic proliferation assay was performed to estimate the half maximal inhibitory concentration (IC50). AGS cells were divided into control, and nintedanib-treated groups (5 µM, 48 h), and differential protein expression was investigated using tandem mass tags (TMT) proteomics. The molecular mechanisms of these differentially expressed proteins and their network interactions were then analyzed using bioinformatics, and potential nintedanib targets were identified. Results This study identified 845 differentially expressed proteins in the nintedanib-treated group (compared to the control group), comprising 526 up-regulated and 319 down-regulated proteins. Bioinformatics analysis revealed that the differentially expressed proteins were primarily enriched in biological pathways for branched-chain amino acid metabolism, steroid biosynthesis, propionate metabolism, fatty acid metabolism, lysosome, peroxisome, and ferroptosis. Key driver analysis revealed that proteins, such as enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), isocitrate dehydrogenase 1 (IDH1), acyl-CoA oxidase 1 (ACOX1), acyl-CoA oxidase 2 (ACOX2), acyl-CoA oxidase 3 (ACOX3), and acetyl-CoA acyltransferase 1 (ACAA1) could be linked with nintedanib action. Conclusion Nintedanib inhibits the proliferation, invasion, and metastasis of gastric cancer cells. The crossover pathways and protein networks predicted by proteomics should provide more detailed molecular information enabling the use of nintedanib against gastric cancer.
Dong et al. (2024) Proteomic study on nintedanib in gastric cancer cells. PeerJ 12:e16771 https://doi.org/10.7717/peerj.16771