USP22 as a key regulator of glycolysis pathway in osteosarcoma: insights from bioinformatics and experimental approaches
Background Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation. Methods We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways. Results We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1. Conclusions USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.
Zhang et al. (2024) USP22 as a key regulator of glycolysis pathway in osteosarcoma: insights from bioinformatics and experimental approaches. PeerJ 12:e17397 https://doi.org/10.7717/peerj.17397
Vaccine refusal in pregnant women in Kahramanmaraş: a community-based study from Türkiye
Background The global health landscape is increasingly challenged by the rejection of childhood vaccines. This study investigates vaccination reservations and refusal among pregnant women. Methods A cross-sectional study was conducted in Kahramanmaraş, Türkiye, spanning January to March 2019, entailing face to face interviews with 938 pregnant women. The questionnaire collected sociodemographic data and probed vaccination attitudes. The decision to vaccinate the baby was treated as the dependent variable, analyzed alongside sociodemographic factors and other variables. Data underwent evaluation via descriptive analysis, the Chi-square test, and binary logistic regression. Results Participants had a mean age of 27.6 years. Among them 20 (2.1%) expressed intent to either abstain from or partially vaccinate their babies, with 70% citing apprehensions regarding potential vaccine-related harm. Statistical analysis unveiled that higher economic income, elevated parental education level, fewer than two children, reliance on the Internet for vaccination information, and a lack of trust in physicians significantly correlated with vaccine refusal among pregnant women (p < 0.05). Conclusions The study concludes that dissemination of vaccination information by the healthcare professionals, complemented by the enactment of pro-vaccine internet policies holds promise in shaping vaccination behavior.
Okyay et al. (2024) Vaccine refusal in pregnant women in Kahramanmaraş: a community-based study from Türkiye. PeerJ 12:e17409 https://doi.org/10.7717/peerj.17409
Clinical value of serum polyunsaturated fatty acids in patients with gastric polyps
Polyunsaturated fatty acids (PUFAs) are vital nutrients in human physiology and are implicated in various chronic diseases. However, the relationship between PUFAs and gastric polyps remains unclear. This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PUFA levels in the serum of 350 patients, along with analyzing the ω-6 to ω-3 ratio. The results revealed significant differences in the levels of C16:1, C18:1, C18:2, α-C18:3, γ-C18:3, C20:1, C20:4, C20:5, ω-3-C22:5, ω-6-C22:5, and C22:6, as well as ω-6 to ω-3 ratio between the control and gasteic polyp groups. Moreover, setting the threshold for ω-6: ω-3 at 10 revealed a close correlation between polyp occurrence and this ratio. These findings suggest that PUFAs and the ω-6 to ω-3 ratio hold promise as potential early screening markers for gastric polyps. However, further research is imperative to elucidate the underlying mechanisms and therapeutic potential of PUFAs in managing gastric polyps.
Li et al. (2024) Clinical value of serum polyunsaturated fatty acids in patients with gastric polyps. PeerJ 12:e17413 https://doi.org/10.7717/peerj.17413
Nucleolin myocardial-specific knockout exacerbates glucose metabolism disorder in endotoxemia-induced myocardial injury
Background Sepsis-induced myocardial injury, as one of the important complications of sepsis, can significantly increase the mortality of septic patients. Our previous study found that nucleolin affected mitochondrial function in energy synthesis and had a protective effect on septic cardiomyopathy in mice. During sepsis, glucose metabolism disorders aggravated myocardial injury and had a negative effect on septic patients. Objectives We investigated whether nucleolin could regulate glucose metabolism during endotoxemia-induced myocardial injury. Methods The study tested whether the nucleolin cardiac-specific knockout in the mice could affect glucose metabolism through untargeted metabolomics, and the results of metabolomics were verified experimentally in H9C2 cells. The ATP content, lactate production, and oxygen consumption rate (OCR) were evaluated. Results The metabolomics results suggested that glycolytic products were increased in endotoxemia-induced myocardial injury, and that nucleolin myocardial-specific knockout altered oxidative phosphorylation-related pathways. The experiment data showed that TNF-α combined with LPS stimulation could increase the lactate content and the OCR values by about 25%, and decrease the ATP content by about 25%. However, interference with nucleolin expression could further decrease ATP content and OCR values by about 10–20% and partially increase the lactate level in the presence of TNF-α and LPS. However, nucleolin overexpression had the opposite protective effect, which partially reversed the decrease in ATP content and the increase in lactate level. Conclusion Down-regulation of nucleolin can exacerbate glucose metabolism disorders in endotoxemia-induced myocardial injury. Improving glucose metabolism by regulating nucleolin was expected to provide new therapeutic ideas for patients with septic cardiomyopathy.
Tang et al. (2024) Nucleolin myocardial-specific knockout exacerbates glucose metabolism disorder in endotoxemia-induced myocardial injury. PeerJ 12:e17414 https://doi.org/10.7717/peerj.17414
Unpredictable soil conditions can affect the prevalence of a microbial symbiosis
The evolution of symbiotic interactions may be affected by unpredictable conditions. However, a link between prevalence of these conditions and symbiosis has not been widely demonstrated. We test for these associations using Dictyostelium discoideum social amoebae and their bacterial endosymbionts. D. discoideum commonly hosts endosymbiotic bacteria from three taxa: Paraburkholderia, Amoebophilus and Chlamydiae. Three species of facultative Paraburkholderia endosymbionts are the best studied and give hosts the ability to carry prey bacteria through the dispersal stage to new environments. Amoebophilus and Chlamydiae are obligate endosymbiont lineages with no measurable impact on host fitness. We tested whether the frequency of both single infections and coinfections of these symbionts were associated with the unpredictability of their soil environments by using symbiont presence-absence data from D. discoideum isolates from 21 locations across the eastern United States. We found that symbiosis across all infection types, symbiosis with Amoebophilus and Chlamydiae obligate endosymbionts, and symbiosis involving coinfections were not associated with any of our measures. However, unpredictable precipitation was associated with symbiosis in two species of Paraburkholderia, suggesting a link between unpredictable conditions and symbiosis.
Scott et al. (2024) Unpredictable soil conditions can affect the prevalence of a microbial symbiosis. PeerJ 12:e17445 https://doi.org/10.7717/peerj.17445
Influence of purple non-sulfur bacterial augmentation on soil nutrient dynamics and rice (Oryza sativa) growth in acidic saline-stressed environments
The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB (Luteovulum sphaeroides EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3–4‰ resulted in an increase in the Na+ accumulation in soil, resulting in a lower rice grain yield by 12.9–22.2% in comparison with the 0‰ salinity case. Supplying the mixture of L. sphaeroides EPS18, EPS37, and EPS54 increased pH by 0.13, NH4+ by 2.30 mg NH4+ kg−1, and available P by 8.80 mg P kg−1, and decreased Na+ by 0.348 meq Na+ 100 g−1, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of L. sphaeroides EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment.
Khuong et al. (2024) Influence of purple non-sulfur bacterial augmentation on soil nutrient dynamics and rice (Oryza sativa) growth in acidic saline-stressed environments. PeerJ 12:e16943 https://doi.org/10.7717/peerj.16943
TPX2 upregulates MMP13 to promote the progression of lipopolysaccharide-induced osteoarthritis
Purpose This study seeks to identify potential clinical biomarkers for osteoarthritis (OA) using bioinformatics and investigate OA mechanisms through cellular assays. Methods Differentially Expressed Genes (DEGs) from GSE52042 (four OA samples, four control samples) were screened and analyzed with protein-protein interaction (PPI) analysis. Overlapping genes in GSE52042 and GSE206848 (seven OA samples, and seven control samples) were identified and evaluated using Gene Set Enrichment Analysis (GSEA) and clinical diagnostic value analysis to determine the hub gene. Finally, whether and how the hub gene impacts LPS-induced OA progression was explored by in vitro experiments, including Western blotting (WB), co-immunoprecipitation (Co-IP), flow cytometry, etc. Result Bioinformatics analysis of DEGs (142 up-regulated and 171 down-regulated) in GSE52042 identified two overlapping genes (U2AF2, TPX2) that exhibit significant clinical diagnostic value. These genes are up-regulated in OA samples from both GSE52042 and GSE206848 datasets. Notably, TPX2, which AUC = 0.873 was identified as the hub gene. In vitro experiments have demonstrated that silencing TPX2 can alleviate damage to chondrocytes induced by lipopolysaccharide (LPS). Furthermore, there is a protein interaction between TPX2 and MMP13 in OA. Excessive MMP13 can attenuate the effects of TPX2 knockdown on LPS-induced changes in OA protein expression, cell growth, and apoptosis. Conclusion In conclusion, our findings shed light on the molecular mechanisms of OA and suggested TPX2 as a potential therapeutic target. TPX2 could promote the progression of LPS-induced OA by up-regulating the expression of MMP13, which provides some implications for clinical research.
Yu et al. (2024) TPX2 upregulates MMP13 to promote the progression of lipopolysaccharide-induced osteoarthritis. PeerJ 12:e17032 https://doi.org/10.7717/peerj.17032
Changes in the concentration of bone turnover markers in men after maximum intensity exercise
Background Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise. Methods The study involved 33 men aged 20–25, divided into two groups: experimental (n = 15) and control (n = 18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined. Results When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 (p = 0.025), b-ALP (p < 0.001), OC (p = 0.004) and PINP (p = 0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP (p < 0.001), NTx1 (p < 0.001), OPG (p = 0.001) and PINP (p = 0.002). Conclusion A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.
Bagińska et al. (2024) Changes in the concentration of bone turnover markers in men after maximum intensity exercise. PeerJ 12:e17258 https://doi.org/10.7717/peerj.17258
Orbicularis oculi muscle activity during computer reading under different degrees of artificially-induced aniseikonia
Background Aniseikonia is a binocular vision disorder that has been associated with asthenopic symptoms. However, asthenopia has been evaluated with subjective tests that make difficult to determine the level of aniseikonia. This study aims to objectively evaluate the impact of induced aniseikonia at different levels on visual fatigue by measuring the orbicularis oculi muscle activity in the dominant and non-dominant eyes while performing a reading task. Methods Twenty-four collegiate students (24.00 ± 3.86 years) participated in this study. Participants read a passage for 7 minutes under four degrees of aniseikonia (0%, 3%, 5% and 10%) at 50 cm. Orbicularis oculi muscle activity of the dominant and non-dominant eye was recorded by surface electromyography. In addition, visual discomfort was assessed after each task by completing a questionnaire. Results Orbicularis oculi muscle activity increased under induced aniseikonia (i.e., greater values for the 10% condition in comparison to 0%, and 3% conditions (p = 0.034 and p = 0.023, respectively)). No statistically significant differences were observed in orbicularis oculi muscle activity for the time on task and between the dominant and non-dominant eyes. Additionally, higher levels of subjective visual discomfort were observed for lower degrees of induced aniseikonia. Conclusion Induced aniseikonia increases visual fatigue at high aniseikonia degrees as measured by the orbicularis oculi muscle activity, and at low degrees as measured with subjective questionnaires. These findings may be of relevance to better understand the visual symptomatology of aniseikonia.
Redondo et al. (2024) Orbicularis oculi muscle activity during computer reading under different degrees of artificially-induced aniseikonia. PeerJ 12:e17293 https://doi.org/10.7717/peerj.17293
Bacteriogenic synthesis of morphologically diverse silver nanoparticles and their assessment for methyl orange dye removal and antimicrobial activity
Nanotechnology and nanoparticles have gained massive attention in the scientific community in recent years due to their valuable properties. Among various AgNPs synthesis methods, microbial approaches offer distinct advantages in terms of cost-effectiveness, biocompatibility, and eco-friendliness. In the present research work, investigators have synthesized three different types of silver nanoparticles (AgNPs), namely AgNPs-K, AgNPs-M, and AgNPs-E, by using Klebsiella pneumoniae (MBC34), Micrococcus luteus (MBC23), and Enterobacter aerogenes (MBX6), respectively. The morphological, chemical, and elemental features of the synthesized AgNPs were analyzed by using UV-Vis spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and energy-dispersive spectroscopy (EDX). UV-Vis absorbance peaks were obtained at 475, 428, and 503 nm for AgNPs-K, AgNPs-M, and AgNPs-E, respectively. The XRD analysis confirmed the crystalline nature of the synthesized AgNPs, having peaks at 26.2°, 32.1°, and 47.2°. At the same time, the FTIR showed bands at 599, 963, 1,693, 2,299, 2,891, and 3,780 cm−1 for all the types of AgNPs indicating the presence of bacterial biomolecules with the developed AgNPs. The size and morphology of the AgNPs varied from 10 nm to several microns and exhibited spherical to porous sheets-like structures. The percentage of Ag varied from 37.8% (wt.%) to 61.6%, i.e., highest in AgNPs-K and lowest in AgNPs-M. Furthermore, the synthesized AgNPs exhibited potential for environmental remediation, with AgNPs-M exhibiting the highest removal efficiency (19.24% at 120 min) for methyl orange dye in simulated wastewater. Further, all three types of AgNPs were evaluated for the removal of methyl orange dye from the simulated wastewater, where the highest dye removal percentage was 19.24% at 120 min by AgNPs-M. Antibacterial potential of the synthesized AgNPs assessment against both Gram-positive (GPB) Bacillus subtilis (MBC23), B. cereus (MBC24), and Gram-negative bacteria Enterococcus faecalis (MBP13) revealed promising results, with AgNPs-M, exhibiting the largest zone of inhibition (12 mm) against GPB B. megaterium. Such investigation exhibits the potential of the bacteria for the synthesis of AgNPs with diverse morphology and potential applications in environmental remediation and antibacterial therapy-based synthesis of AgNPs.
Environmental Contamination and Remediation
Patel et al. (2024) Bacteriogenic synthesis of morphologically diverse silver nanoparticles and their assessment for methyl orange dye removal and antimicrobial activity. PeerJ 12:e17328 https://doi.org/10.7717/peerj.17328