title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=424 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats link: https://peerj.com/articles/16051 last-modified: 2023-09-11 description: Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0–t), AUC(0–∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0–t), MRT(0–∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats. creator: Su-su Bao creator: Peng-fei Tang creator: Nan-yong Gao creator: Zhong-xiang Xiao creator: Jian-chang Qian creator: Long Zheng creator: Guo-xin Hu creator: Huan-hai Xu uri: https://doi.org/10.7717/peerj.16051 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Bao et al. title: Physical activity and health-related quality of life among adults living in Jeddah city Saudi Arabia link: https://peerj.com/articles/16059 last-modified: 2023-09-11 description: BackgroundPhysical activity can improve health-related quality of life (HRQoL) in adults. However, the effect of physical activity on quality of life is unclear among the Saudi adult population. The study aimed to determine the association between physical activity and HRQoL in apparently healthy adults in Jeddah, Saudi Arabia.MethodsThis cross-sectional study was conducted among visitors of shopping malls, walking tracks/fitness centres/gyms and governmental hospitals in Jeddah from March to September 2022. Physical activity was measured with the electronic template of the general practice physical activity questionnaire (GPPAQ), while the HRQoL was measured using the 36-Item Short Form Survey (SF-36) questionnaire. A multiple linear regression model investigated the relationship between physical activity and HRQoL.ResultsA total of 693 individuals participated in this study, with a mean age of 36 (±11). Individuals who fall in the active category of the physical activity level were mostly younger men (37% vs 21%), were non-smokers (30% vs 10%) and had no comorbid condition (29% vs 15%). After adjusting for covariates, men (adjusted β 4.43, 95% CI [1.44–7.41]) with higher physical activity levels (active-adjusted β 10.11, 95% CI [5.44–14.77]) had better scores on the physical component summary (PCS). Similarly, mental component summary (MCS) scores for men (adjusted β 6.51, 95% CI [3.40–9.63]) and physical activity levels (active-adjusted β 9.77, 95% CI [4.90–14.64]) were high.ConclusionThe article reinforces how physical activity contributes towards each dimension of HRQoL. Physical inactivity is a growing public health challenge in Saudi Arabia, affecting all age groups. Investing in innovative strategies and establishing targeted health education programs for academic institutions and communities are required to enhance healthy habits. Additionally, constructing more local sports facilities and concession packages, especially for the females at the gyms, can motivate individuals and promote physical activity. creator: Ola Akram Abdulrashid creator: Hassan Bin Usman Shah creator: Wijdan Abdulkareem Baeshen creator: Sarah Mohammad Aljuaid creator: Enas Awad Alasmari creator: Rania Ali Baokbah creator: Reema Ali Baokbah creator: Nojoud Mohammed Alamoudi creator: Maha Saleh Alkhelewi creator: Amal Abdullah Turkistani creator: Ahmed Abdullah Alharbi creator: Abdulrehman Ahmed Alghamdi creator: Fawaz Alharthi creator: Mohammad Alcattan creator: Amnah Marwan Haikal uri: https://doi.org/10.7717/peerj.16059 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Abdulrashid et al. title: Evaluating the Turkish validity and reliability of the Brief Illness Perception Questionnaire in periodontal diseases link: https://peerj.com/articles/16065 last-modified: 2023-09-11 description: BackgroundThe Brief Illness Perception Questionnaire (Brief IPQ) is a widely used multifactorial scale that assesses the individuals’ perceptions of illness. Although there are studies investigating the psychometric properties of the Brief IPQ in many languages, the Turkish version of Brief IPQ on periodontal diseases has not been revealed so far. This study aimed to evaluate the Turkish validity and reliability of the Brief IPQ and contribute to the literature. It is also aimed to evaluate the patients’ illness perception with periodontal disease and to reveal the possible effects of the disease on the patients’ daily life.MethodsThis cross-sectional study was conducted with 209 patients with periodontal diseases (137 gingivitis and 72 periodontitis cases). Sociodemographic characteristics and clinical periodontal measurements of all patients were recorded. The Turkish versions of the Brief IPQ and the HAD Scale were applied to the patients via face-to-face. The construct validity was determined using confirmatory factor analysis. Test–retest reliability and internal consistency were performed using ICC test and Cronbach’s alpha, respectively. The concurrent validity was determined by using Spearman’s correlation coefficient.ResultsThe confirmatory factor analysis showed that the scale has one factor. The Spearman’s correlation coefficient results were found 0.843 and 0.854 for concurrent validity. Cronbach’s alpha value of the scale was 0.944 in the internal consistency analysis. ICC value was found to be 0.987 for test-retest reliability. Floor/ceiling effects were considered not to be present.ConclusionsIt was found that the Turkish version of The Brief Illness Perception Questionnaire is valid and reliable. Brief IPQ may be used to determine the illness perception in patients with periodontal diseases. creator: Canan Önder creator: Batuhan Bakirarar uri: https://doi.org/10.7717/peerj.16065 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Önder and Bakirarar title: Protective effect of astaxanthin nanoemulsion on mammalian inner ear hair cells link: https://peerj.com/articles/15562 last-modified: 2023-09-08 description: BackgroundAminoglycoside antibiotics are used for treating certain acute infections. However, these drugs cause ototoxicity by inducing inner ear hair cell death.Aims/ObjectivesWe investigated the protective effect of a nanoemulsion of the carotenoid astaxanthin on mammalian inner ear hair cells against neomycin-induced ototoxicity.Material and MethodsDose-response relationship, quantification of hair cell loss, and reactive oxygen species production were assayed in response to neomycin with and without astaxanthin in cultured utricles of CBA/N mice. In addition, auditory brain response (ABR) and hair cell loss after exposure to the nanoformulation and loud noise were examined in vivo in guinea pigs.ResultsAstaxanthin suppressed neomycin-induced reduction of hair cells by reducing the production of hydroxy radicals. Furthermore, hair cell loss in the second rotation of the cochlea was significantly lower in the astaxanthin group than in the noise-only group.Conclusions and SignificanceThe blood-labyrinth barrier limits the successful delivery of drugs for inner ear complications. However, in the nanoemulsion form, astaxanthin can penetrate the round window (fenestra ovale) membrane, enabling topical administration. Thus, astaxanthin nanoemulsion could be useful in treating ototoxicity in individuals with inner ear complications. creator: Yuki Kobayashi creator: Kazuma Sugahara creator: Yosuke Takemoto creator: Junko Tsuda creator: Yoshinobu Hirose creator: Makoto Hashimoto creator: Hiroshi Yamashita uri: https://doi.org/10.7717/peerj.15562 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Kobayashi et al. title: Ferrostatin-1 post-treatment attenuates acute kidney injury in mice by inhibiting ferritin production and regulating iron uptake-related proteins link: https://peerj.com/articles/15786 last-modified: 2023-09-08 description: BackgroundAcute kidney injury (AKI) is a common and serious medical condition with high morbidity and mortality. Recent research has highlighted ferroptosis, a novel form of programmed cell death, as a potential therapeutic target in mitigating renal tubular injury in AKI. Ferrostatin-1, a specific ferroptosis inhibitor, has been demonstrated to prevent renal injury through ferroptosis inhibition.MethodsUtilizing a murine AKI model, we investigated the effects of Ferrostatin-1 by administering it post-injury. Through high-throughput sequencing and pathological analysis, we focused on the critical role of ferroptosis-related pathways in the treatment.ResultsFerrostatin-1 post-conditioning effectively mitigated oxidative damage and reduced iron content associated with AKI. Additionally, critical ferroptosis-related proteins, such as GPX4, SLC7A11, NRF2, and FTH1, exhibited increased expression levels. In vitro, Ferrostatin-1 treatment of HK-2 cells significantly diminished lipid peroxidation and iron accumulation. Furthermore, Ferrostatin-1 was found to downregulate the PI3K signalling pathway.ConclusionFerrostatin-1 acted as a potential ferroptosis inhibitor with the capacity to enhance antioxidant defences. This study suggests that Ferrostatin-1 could serve as a promising novel strategy for improving the treatment of AKI and promoting recovery from the condition. creator: Yanxiu Zhao creator: Binhua Jiang creator: Dinghui Huang creator: Juxiang Lou creator: Guoshun Li creator: Jianqi Liu creator: Fuhui Duan creator: Yuan Yuan creator: Xiaoyan Su uri: https://doi.org/10.7717/peerj.15786 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Zhao et al. title: Evolution of fertilization ability in obligatorily outcrossing populations of Caenorhabditis elegans link: https://peerj.com/articles/15825 last-modified: 2023-09-08 description: In species reproducing by selfing, the traits connected with outcrossing typically undergo degeneration, a phenomenon called selfing syndrome. In Caenorhabditis elegans nematodes, selfing syndrome affects many traits involved in mating, rendering cross-fertilization highly inefficient. In this study, we investigated the evolution of cross-fertilization efficiency in populations genetically modified to reproduce by obligatory outcrossing. Following the genetic modification, replicate obligatorily outcrossing were maintained for over 100 generations, at either optimal (20 °C) or elevated (24 °C) temperatures, as a part of a broader experimental evolution program. Subsequently, fertilization rates were assayed in the evolving populations, as well as their ancestors who had the obligatory outcrossing introduced but did not go through experimental evolution. Fertilization effectivity was measured by tracking the fractions of fertilized females in age-synchronized populations, through 8 h since reaching adulthood. In order to check the robustness of our measurements, each evolving population was assayed in two or three independent replicate blocks. Indeed, we found high levels of among-block variability in the fertilization trajectories, and in the estimates of divergence between evolving populations and their ancestors. We also identified five populations which appear to have evolved increased fertilization efficiency, relative to their ancestors. However, due to the abovementioned high variability, this set of populations should be treated as candidate, with further replications needed to either confirm or disprove their divergence from ancestors. Furthermore, we also discuss additional observations we have made concerning fertilization trajectories. creator: Joanna K. Palka creator: Alicja Dyba creator: Julia Brzozowska creator: Weronika Antoł creator: Karolina Sychta creator: Zofia M. Prokop uri: https://doi.org/10.7717/peerj.15825 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Palka et al. title: Absence of enterotypes in the human gut microbiomes reanalyzed with non-linear dimensionality reduction methods link: https://peerj.com/articles/15838 last-modified: 2023-09-08 description: Enterotypes of the human gut microbiome have been proposed to be a powerful prognostic tool to evaluate the correlation between lifestyle, nutrition, and disease. However, the number of enterotypes suggested in the literature ranged from two to four. The growth of available metagenome data and the use of exact, non-linear methods of data analysis challenges the very concept of clusters in the multidimensional space of bacterial microbiomes. Using several published human gut microbiome datasets of variable 16S rRNA regions, we demonstrate the presence of a lower-dimensional structure in the microbiome space, with high-dimensional data concentrated near a low-dimensional non-linear submanifold, but the absence of distinct and stable clusters that could represent enterotypes. This observation is robust with regard to diverse combinations of dimensionality reduction techniques and clustering algorithms. creator: Ivan Bulygin creator: Vladislav Shatov creator: Anton Rykachevskiy creator: Arsenii Raiko creator: Alexander Bernstein creator: Evgeny Burnaev creator: Mikhail S. Gelfand uri: https://doi.org/10.7717/peerj.15838 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Bulygin et al. title: EXOSC10 is a novel hepatocellular carcinoma prognostic biomarker: a comprehensive bioinformatics analysis and experiment verification link: https://peerj.com/articles/15860 last-modified: 2023-09-08 description: BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor. There are few studies on EXOSC10 (exosome component 10) in HCC; however, the importance of EXOSC10 for HCC remains unclear.MethodsIn the study, the prognosis value of EXOSC10 and the immune correlation were explored by bioinformatics. The expression of EXOSC10 was verified by tissue samples from clinical patients and in vitro experiment (liver cancer cell lines HepG2, MHCC97H and Huh-7; normal human liver cell line LO2). Immunohistochemistry (IHC) was used to detect EXOSC10 protein expression in clinical tissue from HCC. Huh-7 cells with siEXOSC10 were constructed using lipofectamine 3000. Cell counting kit 8 (CCK-8) and colony formation were used to test cell proliferation. The wound healing and transwell were used to analyze the cell migration capacity. Mitochondrial membrane potential, Hoechst 33342 dye, and flow cytometer were used to detect the change in cell apoptosis, respectively. Differential expression genes (DEGs) analysis and gene set enrichment analysis (GSEA) were used to investigate the potential mechanism of EXOSC10 and were verified by western blotting.ResultsEXOSC10 was highly expressed in tissues from patients with HCC and was an independent prognostic factor for overall survival (OS) in HCC. Increased expression of EXOSC10 was significantly related to histological grade, T stage, and pathological stage. Multivariate analysis indicated that the high expression level of EXOSC10 was correlated with poor overall survival (OS) in HCC. GO and GSEA analysis showed enrichment of the cell cycle and p53-related signaling pathway. Immune analysis showed that EXOSC10 expression was a significant positive correlation with immune infiltration in HCC. In vitro experiments, cell proliferation and migration were inhibited by the elimination of EXOSC10. Furthermore, the elimination of EXOSC10 induced cell apoptosis, suppressed PARP, N-cadherin and Bcl-2 protein expression levels, while increasing Bax, p21, p53, p-p53, and E-cadherin protein expression levels.ConclusionsEXOSC10 had a predictive value for the prognosis of HCC and may regulate the progression of HCC through the p53-related signaling pathway. creator: Zhi-Yong Meng creator: Yu-Chun Fan creator: Chao-Sheng Zhang creator: Lin-Li Zhang creator: Tong Wu creator: Min-Yu Nong creator: Tian Wang creator: Chuang Chen creator: Li-He Jiang uri: https://doi.org/10.7717/peerj.15860 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Meng et al. title: Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway link: https://peerj.com/articles/15999 last-modified: 2023-09-08 description: Dieting is a basic treatment for lowering hyperuricemia. Here, we aimed to determine the optimal amount of dietary food that lowers serum uric acid (SUA) without modifying the dietary ingredients in rats. Increased SUA was found in food-deprived 45-day-old uricase-deficient rats (Kunming-DY rats), and the optimal amount of dietary food (75% dietary intake) to lower SUA was established by controlling the amount of food given daily from 25% to 100% for 2 weeks. In addition to lowering SUA by approximately 22.5 ± 20.5%, the optimal amount of dietary food given for 2 weeks inhibited urine uric acid excretion, lowered the uric acid content in multiple organs, improved renal function, lowered serum triglyceride, alleviated organ injuries (e.g., liver, kidney and intestinal tract) at the histological level, and down-regulated the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway of the cell cycle (ko04110). Taken together, these results demonstrate that 75% dietary food effectively lowers the SUA level without modifying dietary ingredients and alleviates the injuries resulting from uricase deficiency or hyperuricemia, the mechanism of which is associated with the down-regulation of the cell cycle pathway. creator: Yun Yu creator: Xulian Wan creator: Dan Li creator: Yalin Qi creator: Ning Li creator: Guangyun Luo creator: Hua Yin creator: Lei Wang creator: Wan Qin creator: Yongkun Li creator: Lvyu Li creator: Weigang Duan uri: https://doi.org/10.7717/peerj.15999 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Yu et al. title: Predictors of one-year mortality following hip fracture surgery in elderly link: https://peerj.com/articles/16008 last-modified: 2023-09-08 description: BackgroundUnderstanding mortality risk factors is critical to reducing mortality among elderly hip fracture patients. To investigate the effects of admission and post-operative levels of distribution width of red blood cells (RDW), albumin, and RDW/albumin (RA) ratio on predicting 1-year mortality following hip fracture surgery.MethodsA retrospective study was conducted on 275 elderly patients who underwent hip fracture surgery in a tertiary hospital between January 2018 and January 2022. Deaths within one year of hip fracture were defined as the deceased group. The survivors were defined as those who survived for at least one year. The relationship between admission and post-operative levels of RDW, albumin, RA, and mortality within one year after hip surgery was assessed statistically, including binary logistic regression analysis. The study also assessed other factors related to mortality.ResultsOne-year mortality was 34.7%. There was a 3.03-year (95% CI [1.32–4.75]) difference between the deceased (79.55 ± 8.36 years) and survivors (82.58 ± 7.41 years) (p < 0.001). In the deceased group, the mean hemoglobin (HGB) values at admission (p = 0.022) and post-operative (p = 0.04) were significantly lower. RDW values at admission (p = 0.001) and post-op (p = 0.001) were significantly lower in the survivor group. The mean albumin values at admission (p < 0.001) and post-operative (p < 0.001) in the survivor group were significantly higher than in the deceased group. A significant difference was found between the survivor group and the deceased group in terms of mean RA ratio at admission and post-operative (p < 0.001). Based on binary logistic regression analysis, presence of chronic obstructive pulmonary disease (COPD) (OR 3.73, 95% CI [1.8–7.76]), RDW (OR 1.78, 95% CI [1.48–2.14]), and albumin (OR 0.81, 95% CI [0.75–0.87]), values at admission were found to be independent predictors of 1-year mortality in elderly patients with hip fracture.ConclusionBased on this study, presence of COPD, higher RDW, and lower albumin levels at admission were independent predictors of 1-year mortality following hip fracture surgery in the elderly. creator: Mehmet Özel creator: Mustafa Altıntaş creator: Ali Cankut Tatlıparmak uri: https://doi.org/10.7717/peerj.16008 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Özel et al.