title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=491 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Analysis of self-renewing and differentiation-related microRNAs and transcription factors in multilineage mouse hematopoietic stem/progenitor cells induced by 1,4-benzoquinone link: https://peerj.com/articles/15608 last-modified: 2023-07-10 description: BackgroundHSPCs are targets for benzene-induced hematotoxicity and leukemogenesis. However, benzene toxicity targeting microRNAs (miRNAs) and transcription factors (TF) that are involve in regulating self-renewing and differentiation of HSPCs comprising of different hematopoietic lineages remains poorly understood. In this study, the effect of a benzene metabolite, 1,4-benzoquinone (1,4-BQ) exposure, in HSPCs focusing on the self-renewing (miRNAs: miR-196b and miR-29a; TF: HoxB4, Bmi-1) and differentiation (miRNAs: miR-181a, TF: GATA3) pathways were investigated.MethodsFreshly isolated mouse BM cells were initially exposed to 1,4-BQ at 1.25 to 5 µM for 24 h, followed by miRNAs and TF studies in BM cells. Then, the miRNAs expression was further evaluated in HSPCs of different lineages comprised of myeloid, erythroid and pre-B lymphoid progenitors following 7–14 days of colony forming unit (CFU) assay.ResultsExposure to 1,4-BQ in BM cells significantly (p < 0.05) reduced the miR-196b (2.5 and 5 µM), miR-181a (1.25, 2.5 and 5 µM) and miR-29a (1.25 µM) along with upregulation of miR-29a at 2.5 µM. Meanwhile, 1,4-BQ exposure in HSPCs significantly increased the miR-196b expression level (p < 0.05) only in myeloid and pre-B lymphoid progenitors at 2.5 and 5 µM. Significant (p < 0.05) reduction in expression of miR-181a in myeloid (1.25 µM), erythroid (5 µM) progenitors along with miR-29a in myeloid (1.25 µM) and pre-B lymphoid (5 µM) progenitors were noted following exposure to 1,4-BQ. Meanwhile, increased expression of miR-181a was observed in pre-B lymphoid progenitor upon exposure to 1,4-BQ, but only at 5 µM. As for TF studies, expression of HoxB4 protein was significantly increased (p < 0.05) at all 1,4-BQ concentrations as compared to Bmi-1 and GATA3, which were significantly (p < 0.05) elevated starting at 2.5 µM of 1,4-BQ.Conclusion1,4-BQ induces aberration of miRNAs and transcription factors protein expression that are involved in regulating self-renewing and differentiation pathways of HSPCs. Moreover, epigenetic toxicity as evidenced from the miRNAs expression was found to be mediated by a lineage-driven mechanism. The role of cell lineage in governing the toxicity of 1,4-BQ in HSPCs lineages deserves further investigation. creator: Ramya Dewi creator: Nur Afizah Yusoff creator: Siti Razila Abdul Razak creator: Zariyantey Abd Hamid uri: https://doi.org/10.7717/peerj.15608 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Dewi et al. title: Network neighborhood operates as a drug repositioning method for cancer treatment link: https://peerj.com/articles/15624 last-modified: 2023-07-10 description: Computational drug repositioning approaches are important, as they cost less compared to the traditional drug development processes. This study proposes a novel network-based drug repositioning approach, which computes similarities between disease-causing genes and drug-affected genes in a network topology to suggest candidate drugs with highest similarity scores. This new method aims to identify better treatment options by integrating systems biology approaches. It uses a protein-protein interaction network that is the main topology to compute a similarity score between candidate drugs and disease-causing genes. The disease-causing genes were mapped on this network structure. Transcriptome profiles of drug candidates were taken from the LINCS project and mapped individually on the network structure. The similarity of these two networks was calculated by different network neighborhood metrics, including Adamic-Adar, PageRank and neighborhood scoring. The proposed approach identifies the best candidates by choosing the drugs with significant similarity scores. The method was experimented on melanoma, colorectal, and prostate cancers. Several candidate drugs were predicted by applying AUC values of 0.6 or higher. Some of the predictions were approved by clinical phase trials or other in-vivo studies found in literature. The proposed drug repositioning approach would suggest better treatment options with integration of functional information between genes and transcriptome level effects of drug perturbations and diseases. creator: Ali Cüvitoğlu creator: Zerrin Isik uri: https://doi.org/10.7717/peerj.15624 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Cüvitoğlu and Isik title: Effect of prolactin on cytotoxicity and oxidative stress in ovine ovarian granulosa cells link: https://peerj.com/articles/15629 last-modified: 2023-07-10 description: BackgroundProlactin (PRL) has been reported to be associated with oxidative stress, which is an important contributor leading to cell apoptosis. However, little is known about the mechanisms underlying the effects of PRL on cytotoxicity and oxidative stress in ovine ovarian granulosa cells (GCs).MethodsOvine ovarian GCs were treated with 0, 4, 20, 100 and 500 ng/mL of PRL. Then, the cytotoxicity, cell viability, malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) of GCs were detected. Additionally, 500 ng/mL PRL was chosen as the high PRL concentration (HPC) due to its high cytotoxicity and oxidative stress. Proteomic and metabonomic were performed to examine the overall difference in proteins and metabolic pathways between C (control: 0 ng/mL PRL) and P groups (500 ng/mL PRL).ResultsThe results indicated that GCs treated with 4 ng/mL PRL significantly decreased (P < 0.05) the cytotoxicity, ROS and MDA, increased (P < 0.05) the cell viability, SOD and T-AOC, and the GCs treated with 500 ng/mL PRL showed the opposite trend (P < 0.05). Supplementation with 500 ng/mL PRL significantly increased the proteins of MT-ND1, MAPK12, UBA52 and BCL2L1, which were enriched in ROS and mitophagy pathways. Pathway enrichment analysis showed that the pentose phosphate pathway was significantly enriched in the P group.ConclusionA low concentration of PRL inhibited cytotoxicity and oxidative stress. HPC induced oxidative stress in ovine ovarian GCs via the pentose phosphate pathway by modulating the associated proteins MT-ND1 in ROS pathway and UBA52, MAPK12 and BCL2L1 in mitophagy pathway, resulting in cytotoxicity. creator: Ruochen Yang creator: Shuo Zhang creator: Chunhui Duan creator: Yunxia Guo creator: Xinyu Shan creator: Xinyan Zhang creator: Sicong Yue creator: Yingjie Zhang creator: Yueqin Liu uri: https://doi.org/10.7717/peerj.15629 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Yang et al. title: Role of microRNA miR171 in plant development link: https://peerj.com/articles/15632 last-modified: 2023-07-10 description: MicroRNAs (miRNAs) are endogenous non-coding small RNA with 19–24 nucleotides (nts) in length, which play an essential role in regulating gene expression at the post-transcriptional level. As one of the first miRNAs found in plants, miR171 is a typical class of conserved miRNAs. The miR171 sequences among different species are highly similar, and the vast majority of them have both “GAGCCG” and “CAAUAU” fragments. In addition to being involved in plant growth and development, hormone signaling and stress response, miR171 also plays multiple and important roles in plants through interactions with microbe and other small-RNAs. The miRNA functions by regulating the expression of target genes. Most of miR171’s target genes are in the GRAS gene family, but also include some NSP, miRNAs, lncRNAs, and other genes. This review is intended to summarize recent updates on miR171 regarding its function in plant life and hopefully provide new ideas for understanding miR171 function and regulatory mechanisms. creator: Ling Ling Pei creator: Ling Ling Zhang creator: Xin Liu creator: Jing Jiang uri: https://doi.org/10.7717/peerj.15632 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Pei et al. title: Identification of key biomarkers based on the proliferation of secondary hyperparathyroidism by bioinformatics analysis and machine learning link: https://peerj.com/articles/15633 last-modified: 2023-07-10 description: ObjectiveSecondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify potential biomarkers that may be used to predict the progression of SHPT and to elucidate the molecular mechanisms of SHPT pathogenesis at the transcriptome level.MethodsWe analyzed differentially expressed genes (DEGs) between diffuse and nodular parathyroid hyperplasia of SHPT patients from the GSE75886 dataset, and then verified DEG levels with the GSE83421 data file of primary hyperparathyroidism (PHPT) patients. Candidate gene sets were selected by machine learning screens of differential genes and immune cell infiltration was explored with the CIBERSORT algorithm. RcisTarget was used to predict transcription factors, and Cytoscape was used to construct a lncRNA-miRNA-mRNA network to identify possible molecular mechanisms. Immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the expression of screened genes in parathyroid tissues of SHPT patients and animal models.ResultsA total of 614 DEGs in GSE75886 were obtained as candidate gene sets for further analysis. Five key genes (USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2) had significant expression differences between groups and were screened with the best ranking in the machine learning process. These genes were shown to be closely related to immune cell infiltration levels and play important roles in the immune microenvironment. Transcription factor ZBTB6 was identified as the master regulator, alongside multiple other transcription factors. Combined with qPCR and IHC assay of hyperplastic parathyroid tissues from SHPT patients and rats confirm differential expression of USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2, suggesting that they may play important roles in the proliferation and progression of SHPT.ConclusionUSP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2 have great potential both as biomarkers and as therapeutic targets in the proliferation of SHPT. These findings suggest novel potential targets and future directions for SHPT research. creator: Aiwen Shen creator: Jialin Shi creator: Yu Wang creator: Qian Zhang creator: Jing Chen uri: https://doi.org/10.7717/peerj.15633 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Shen et al. title: Evaluation of sugarcane promising clones based on the morphophysiological traits developed from fuzz link: https://peerj.com/articles/15646 last-modified: 2023-07-10 description: Sugarcane is one of the critical commercial crops and principal sources of ethanol and sugar worldwide. Unfavorable conditions and poor seed setting rates hinder variety development in sugarcane. Countries like Pakistan directly import fuzz (true seed) and other propagation material from the USA, China, Brazil, etc. In this study, we imported fuzz from China, developed 29 genotypes germinating in the glasshouse, and evaluated at field conditions along with two local checks (CPF-251 and HSF-240). Morphophysiological data were recorded, including plant height (PH), cane length (CL), internodal length (IL), tiller number (TN), brix percentage (B), cane diameter (CD), chlorophyll a (Chl. a), chlorophyll b (Chl. b), and total chlorophyll (T. Chl). Results showed highly significant (p < 0.001) differences among the sugarcane accessions for all the studied traits. High broad-sense heritability (81.89% to 99.91%) was recorded for all the studied parameters. Genetic Advance (GA) ranges from 4.6% to 65.32%. The highest GA was observed for PH (65.32%), followed by CL (63.28%). Chlorophyll leaching assay was also performed at different time points (0, 50, 100, 150, and 200 min). All the genotypes showed the same leaching trend at all times, and better performing genotypes showed less leaching compared to poor performing, indicating the high amount of cutin and wax on the leaf surface. Correlation analysis showed that PH, CL, IL, and TN had significant associations. Principal components analysis (PCA) further confirms these results. Based on PCA and correlation results, PH, CL, IL, and TN can be utilized as a selection criterion for sugarcane improvement. Genotypes such as NS-4a, NS-5, NS-6, NS-8, NS-9, and NS-15 are recommended for future breeding programs related to sugarcane variety development. creator: Bilal Saleem creator: Muhammad Uzair creator: Muhammad Noman creator: Kotb A. Attia creator: Muqing Zhang creator: Mona S. Alwahaibi creator: Nageen Zahra creator: Muhammad Kashif Naeem creator: Arif A. Mohammed creator: Sajid Fiaz creator: Itoh Kimiko creator: Muhammad Ramzan Khan uri: https://doi.org/10.7717/peerj.15646 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Saleem et al. title: Toxic effects of sodium dodecyl sulfate on planarian Dugesia japonica link: https://peerj.com/articles/15660 last-modified: 2023-07-10 description: Sodium dodecyl sulfate (SDS) is an anionic surfactant, which is widely used in various fields in human life. However, SDS discharged into the water environment has a certain impact on aquatic organisms. In this study, planarian Dugesia japonica (D. japonica) was used to identify the toxic effects of SDS. A series of SDS solutions with different concentrations were used to treat planarians for the acute toxicity test , and the results showed that the semi-lethal concentration (LC50) of SDS to D. japonica at 24 h, 48 h, 72 h, and 96 h were 4.29 mg/L, 3.76 mg/L, 3.45 mg/L, and 3.20 mg/L respectively. After the planarians were exposed to 0.5 mg/L and 1.0 mg/L SDS solutions for 1, 3, and 5 days, the activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) content were measured to detect the oxidative stress and lipid peroxidation in planarians. Random amplified polymorphic DNA (RAPD) analysis was performed to detect the genotoxicity caused by SDS to planarians. The results showed that the activities of SOD, CAT, and MDA content increased after the treatment, indicating that SDS induced oxidative stress in planarians. RAPD analysis showed that the genomic template stability (GTS) values of planarians treated by 0.5 mg/L and 1.0 mg/L SDS for 1, 3, and 5 days were 67.86%, 64.29%, 58.93%, and 64.29%, 60.71%, 48.21%, respectively. GTS values decreased with the increasing of SDS concentration and exposure time, indicating that SDS had genotoxicity to planarians in a time and dose-related manner. Fluorescent quantitative PCR (qPCR) was used to investigate the effects of SDS on gene expression of planarians. After the planarians were exposed to 1.0 mg/L SDS solution for 1, 3, and 5 days, the expression of caspase3 was upregulated, and that of piwiA, piwiB, PCNA, cyclinB, and RAD51 were downregulated. These results suggested that SDS might induce apoptosis, affect cell proliferation, differentiation, and DNA repair ability of planarian cells and cause toxic effects on planarian D. japonica. creator: Minmin Feng creator: Zhenbiao Xu creator: Dandan Yin creator: Zelong Zhao creator: Xiuyuan Zhou creator: Linxia Song uri: https://doi.org/10.7717/peerj.15660 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Feng et al. title: Varying intensities of chronic stress induce inconsistent responses in weight and plasma metabolites in house sparrows (Passer domesticus) link: https://peerj.com/articles/15661 last-modified: 2023-07-10 description: One of the biggest unanswered questions in the field of stress physiology is whether variation in chronic stress intensity will produce proportional (a gradient or graded) physiological response. We were specifically interested in the timing of the entrance into homeostatic overload, or the start of chronic stress symptoms. To attempt to fill this knowledge gap we split 40 captive house sparrows (Passer domesticus) into four groups (high stress, medium stress, low stress, and a captivity-only control) and subjected them to six bouts of chronic stress over a 6-month period. We varied the number of stressors/day and the length of each individual bout with the goal of producing groups that would experience different magnitudes of wear-and-tear. To evaluate the impact of chronic stress, at the start and end of each stress bout we measured body weight and three plasma metabolites (glucose, ketones, and uric acid) in both a fasted and fed state. All metrics showed significant differences across treatment groups, with the high stress group most frequently showing the greatest changes. However, the changes did not produce a consistent profile that matched the different chronic stress intensities. We also took samples after a prolonged recovery period of 6 weeks after the chronic stressors ended. The only group difference that persisted after 6 weeks was weight—all differences across groups in metabolites recovered. The results indicate that common blood metabolites are sensitive to stressors and may show signs of wear-and-tear, but are not reliable indicators of the intensity of long-term chronic stress. Furthermore, regulatory mechanisms are robust enough to recover within 6 weeks post-stress. creator: Ursula K. Beattie creator: Nina Fefferman creator: L. Michael Romero uri: https://doi.org/10.7717/peerj.15661 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Beattie et al. title: Alteration of the oral and gut microbiota in patients with Kawasaki disease link: https://peerj.com/articles/15662 last-modified: 2023-07-10 description: BackgroundKawasaki disease (KD) is a multi-systemic vasculitis that primarily affects children and has an unknown cause. Although an increasing number of studies linking the gut microbiota with KD, the unchallengeable etiology of KD is not available.MethodsHere, we obtained fecal and oral samples from KD patients and healthy controls, and then we use high-throughput sequencing to examine the diversity and composition of microbiota.ResultsResults showed that both in the gut and oral microbiota, the diversity of KD patients was significantly lower than that of the healthy controls. In the gut microbiota, a higher abundance of Enterococcus (40.12% vs less than 0.1%), Bifidobacterium (20.71% vs 3.06%), Escherichia-Shigella (17.56% vs 0.61%), Streptococcus (5.97% vs 0.11%) and Blautia (4.69% vs 0.1%) was observed in the KD patients, and enrichment of Enterococcus in the patients was observed. In terms of oral microbiota, the prevalence of Streptococcus (21.99% vs 0.1%), Rothia (3.02% vs 0.1%), and Escherichia-Shigella (0.68% vs 0.0%) were significantly higher in the KD patients, with the enrichment of Streptococcus and Escherichia-Shigella. Additionally, significant differences in microbial community function between KD patients and healthy controls in the fecal samples were also observed, which will affect the colonization and reproduction of gut microbiota.ConclusionsThese results suggested that the dysbiosis of gut and oral microbiota are both related to KD pathogenesis, of which, the prevalence of Enterococcus in the gut and higher abundance of Streptococcus and Escherichia-Shigella in the oral cavity will be a potential biomarker of the KD. Overall, this study not only confirms that the disturbance of gut microbiota is a causative trigger of KD but also provides new insight into the oral microbiota involved in KD pathogenesis. creator: Qinghuang Zeng creator: Renhe Zeng creator: Jianbin Ye uri: https://doi.org/10.7717/peerj.15662 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Zeng et al. title: Track cycling sprint sex differences using power data link: https://peerj.com/articles/15671 last-modified: 2023-07-10 description: ObjectivesCurrently, there are no data on sex differences in the power profiles in sprint track cycling. This cross-section study analyses retrospective data of female and male track sprint cyclists for sex differences. We hypothesized that women would exhibit lower peak power to weight than men, as well as demonstrate a different distribution of power durations related to sprint cycling performance.DesignWe used training, testing, and racing data from a publicly available online depository (www.strava.com), for 29 track sprint cyclists (eight women providing 18 datasets, and 21 men providing 54 datasets) to create sex-specific profiles. R2 was used to describe model quality, and regression indices are used to compare watts per kilogram (W/kg) for each duration for both sexes against a 1:1 relationship expected for 15-s:15-s W/kg.ResultsWe confirmed our sample were sprint cyclists, displaying higher peak and competition power than track endurance cyclists. All power profiles showed a high model quality (R2 ≥ 0.77). Regression indices for both sexes were similar for all durations, suggesting similar peak power and similar relationship between peak power and endurance level for both men and women (rejecting our hypothesis). The value of R2 for the female sprinters showed greater variation suggesting greater differences within female sprint cyclists.ConclusionThe main finding shows female sprint cyclists in this study have very similar relationships between peak power and endurance power as men. Higher variation in W/kg for women in this study than men, within these strong relationships, indicates women in this study, had greater inter-athlete variability, and may thus require more personalised training. Future work needs to be performed with larger samples, and at different levels to optimize these recommendations. creator: Hamish Ferguson creator: Chris Harnish creator: Sebastian Klich creator: Kamil Michalik creator: Anna Katharina Dunst creator: Tony Zhou creator: J Geoffrey Chase uri: https://doi.org/10.7717/peerj.15671 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Ferguson et al.