A comprehensive analysis of the oncogenic and prognostic role of TBC1Ds in human hepatocellular carcinoma
Backgrounds TBC1D family members (TBC1Ds) are a group of proteins that contain the Tre2-Bub2-Cdc16 (TBC) domain. Recent studies have shown that TBC1Ds are involved in tumor growth, but no analysis has been done of expression patterns and prognostic values of TBC1Ds in hepatocellular carcinoma (HCC). Methods The expression levels of TBC1Ds were evaluated in HCC using the TIMER, UALCN and Protein Atlas databases. The correlation between the mRNA levels of TBC1Ds and the prognosis of patients with HCC in the GEPIA database was then analyzed. An enrichment analysis then revealed genes that potentially interact with TBC1Ds. The correlation between levels of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC were studied using the TIMER 2.0 database. Finally, a series of in vitro assays verified the role of TBC1Ds in HCC progression. Results This study revealed the upregulated expression of TBC1Ds in HCC and the strong positive correlation between the mRNA levels of TBC1Ds and poor prognosis of patients with HCC. The functions of TBC1Ds were mainly related to autophagy and the AMPK pathway. There was also a significant correlation between level of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC. The promoting role of TBC1Ds in HCC progression was verified in vitro assays. Conclusion The results of this analysis indicate that TBC1Ds may serve as new biomarkers for early diagnosis and treatment of HCC.
Zhang et al. (2024) A comprehensive analysis of the oncogenic and prognostic role of TBC1Ds in human hepatocellular carcinoma. PeerJ 12:e17362 https://doi.org/10.7717/peerj.17362
Arsenic disulfide promoted the demethylation of PTPL1 in diffuse large B cell lymphoma cells
Background Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on PTPL1 methylation in diffuse large B cell lymphoma (DLBCL). Methods We knocked down the expression of PTPL1 in two DLBCL cell lines (i.e., DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of PTPL1 knockdown. The methylation of PTPL1 in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the PTPL1 methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of DNMT1, DNMT3B and MBD2 was determined. Results PTPL1 functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that PTPL1 knockdown promoted the proliferation of DLBCL cells. PTPL1 was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the PTPL1 demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2. Conclusion Experimental evidence shows that PTPL1 functions as a tumor suppressor gene in DLBCL progression. PTPL1 hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner.
Chen et al. (2024) Arsenic disulfide promoted the demethylation of PTPL1 in diffuse large B cell lymphoma cells. PeerJ 12:e17363 https://doi.org/10.7717/peerj.17363
Non-destructive prediction of anthocyanin concentration in whole eggplant peel using hyperspectral imaging
Accurately detecting the anthocyanin content in eggplant peel is essential for effective eggplant breeding. The present study aims to present a method that combines hyperspectral imaging with advanced computational analysis to rapidly, non-destructively, and precisely measure anthocyanin content in eggplant fruit. For this purpose, hyperspectral images of the fruits of 20 varieties with diverse colors were collected, and the content of the anthocyanin were detected using high performance liquid chromatography (HPLC) methods. In order to minimize background noise in the hyperspectral images, five preprocessing algorithms were utilized on average reflectance spectra: standard normalized variate (SNV), autoscales (AUT), normalization (NOR), Savitzky–Golay convolutional smoothing (SG), and mean centering (MC). Additionally, the competitive adaptive reweighted sampling (CARS) method was employed to reduce the dimensionality of the high-dimensional hyperspectral data. In order to predict the cyanidin, petunidin, delphinidin, and total anthocyanin content of eggplant fruit, two models were constructed: partial least squares regression (PLSR) and least squares support vector machine (LS-SVM). The HPLC results showed that eggplant peel primarily contains three types of anthocyanins. Furthermore, there were significant differences in the average reflectance rates between 400–750 nm wavelength ranges for different colors of eggplant peel. The prediction model results indicated that the model based on NOR CARS LS-SVM achieved the best performance, with a squared coefficient of determination (R2) greater than 0.98, RMSEP and RMSEC less than 0.03 for cyanidin, petunidin, delphinidin, and total anthocyanin predication. These results suggest that hyperspectral imaging is a rapid and non-destructive technique for assessing the anthocyanin content of eggplant peel. This approach holds promise for facilitating the more effective eggplant breeding.
Ma et al. (2024) Non-destructive prediction of anthocyanin concentration in whole eggplant peel using hyperspectral imaging. PeerJ 12:e17379 https://doi.org/10.7717/peerj.17379
Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma
Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC. Methods By utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan–Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines in vitro. Results As a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population.
Yuan et al. (2024) Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma. PeerJ 12:e17296 https://doi.org/10.7717/peerj.17296
Alzheimer’s diseases in America, Europe, and Asian regions: a global genetic variation
Background Alzheimer’s disease (AD) is one of the multifaceted neurodegenerative diseases influenced by many genetic and epigenetic factors. Genetic factors are merely not responsible for developing AD in the whole population. The studies of genetic variants can provide significant insights into the molecular basis of Alzheimer’s disease. Our research aimed to show how genetic variants interact with environmental influences in different parts of the world. Methodology We searched PubMed and Google Scholar for articles exploring the relationship between genetic variations and global regions such as America, Europe, and Asia. We aimed to identify common genetic variations susceptible to AD and have no significant heterogeneity. To achieve this, we analyzed 35 single-nucleotide polymorphisms (SNPs) from 17 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, TOMM40, MS4A6A, ARID5B, SORL1, APOC1, MTHFD1L, BDNF, TFAM, and PICALM) from different regions based on previous genomic studies of AD. It has been reported that rs3865444, CD33, is the most common polymorphism in the American and European populations. From TOMM40 and APOE rs2075650, rs429358, and rs6656401, CR1 is the common investigational polymorphism in the Asian population. Conclusion The results of all the research conducted on AD have consistently shown a correlation between genetic variations and the incidence of AD in the populations of each region. This review is expected to be of immense value in future genetic research and precision medicine on AD, as it provides a comprehensive understanding of the genetic factors contributing to the development of this debilitating disease.
Hossain et al. (2024) Alzheimer’s diseases in America, Europe, and Asian regions: a global genetic variation. PeerJ 12:e17339 https://doi.org/10.7717/peerj.17339
A retrospective prognostic evaluation using unsupervised learning in the treatment of COVID-19 patients with hypertension treated with ACEI/ARB drugs
Introduction This study aimed to evaluate the prognosis of patients with COVID-19 and hypertension who were treated with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor B (ARB) drugs and to identify key features affecting patient prognosis using an unsupervised learning method. Methods A large-scale clinical dataset, including patient information, medical history, and laboratory test results, was collected. Two hundred patients with COVID-19 and hypertension were included. After cluster analysis, patients were divided into good and poor prognosis groups. The unsupervised learning method was used to evaluate clinical characteristics and prognosis, and patients were divided into different prognosis groups. The improved wild dog optimization algorithm (IDOA) was used for feature selection and cluster analysis, followed by the IDOA-k-means algorithm. The impact of ACEI/ARB drugs on patient prognosis and key characteristics affecting patient prognosis were also analysed. Results Key features related to prognosis included baseline information and laboratory test results, while clinical symptoms and imaging results had low predictive power. The top six important features were age, hypertension grade, MuLBSTA, ACEI/ARB, NT-proBNP, and high-sensitivity troponin I. These features were consistent with the results of the unsupervised prediction model. A visualization system was developed based on these key features. Conclusion Using unsupervised learning and the improved k-means algorithm, this study accurately analysed the prognosis of patients with COVID-19 and hypertension. The use of ACEI/ARB drugs was found to be a protective factor for poor clinical prognosis. Unsupervised learning methods can be used to differentiate patient populations and assess treatment effects. This study identified important features affecting patient prognosis and developed a visualization system with clinical significance for prognosis assessment and treatment decision-making.
Ge et al. (2024) A retrospective prognostic evaluation using unsupervised learning in the treatment of COVID-19 patients with hypertension treated with ACEI/ARB drugs. PeerJ 12:e17340 https://doi.org/10.7717/peerj.17340
Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis
Background An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman’s correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = −0.460, p = 0.010), as well as gingival index (r = −0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.
Madi et al. (2024) Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis. PeerJ 12:e17374 https://doi.org/10.7717/peerj.17374
Feral frogs, native newts, and chemical cues: identifying threats from and management opportunities for invasive African Clawed Frogs in Washington state
Invasive species threaten biodiversity globally. Amphibians are one of the most threatened vertebrate taxa and are particularly sensitive to invasive species, including other amphibians. African clawed frogs (Xenopus laevis) are native to Southern Africa but have subsequently become invasive on multiple continents—including multiple parts of North America—due to releases from the pet and biomedical trades. Despite their prevalence as a global invader, the impact of X. laevis remains understudied. This includes the Pacific Northwest of the USA, which now hosts multiple expanding X. laevis populations. For many amphibians, chemical cues communicate important information, including the presence of predators. Here, we tested the role chemical cues may play in mediating interactions between feral X. laevis and native amphibians in the Pacific Northwest. We tested whether native red-legged frog (Rana aurora) tadpoles display an antipredator response to non-native frog (X. laevis) or native newt (rough-skinned newts, Taricha granulosa) predator chemical stimuli. We found that R. aurora tadpoles exhibited pronounced anti-predator responses when exposed to chemical cues from T. granulosa but did not display anti-predator response to invasive X. laevis chemical cues. We also began experimentally testing whether T. granulosa—which produce a powerful neurotoxin tetrodotoxin (TTX)—may elicit an anti-predator response in X. laevis, that could serve to deter co-occupation. However, our short-duration experiments found that X. laevis were attracted to newt chemical stimuli rather than deterred. Our findings show that X. laevis likely poses a threat to native amphibians, and that these native species may also be particularly vulnerable to this invasive predator, compared to native predators, because toxic native newts may not limit X. laevis invasions. Our research provides some of the first indications that native Pacific Northwest species may be threatened by feral X. laevis and provides a foundation for future experiments testing potential management techniques for X. laevis.
Anderson et al. (2024) Feral frogs, native newts, and chemical cues: identifying threats from and management opportunities for invasive African Clawed Frogs in Washington state. PeerJ 12:e17307 https://doi.org/10.7717/peerj.17307
The effect of social anxiety on threat acquisition and extinction: a systematic review and meta-analysis
Although exposure-based therapy has been found to be effective at alleviating symptoms of social anxiety disorder, it often does not lead to full remission, and relapse after treatment is common. Exposure therapy is based on theoretical principles of extinction of conditioned fear responses. However, there are inconsistencies in findings across experiments that have investigated the effect of social anxiety on threat conditioning and extinction processes. This systematic review and meta-analysis aimed to examine whether elevated levels of social anxiety are associated with abnormalities in threat conditioning and extinction processes. A second aim was to examine the sensitivity of various study designs and characteristics to detect social anxiety-related differences in threat conditioning and extinction. A systematic search was conducted, which identified twenty-three experiments for inclusion in the review. The findings did not demonstrate compelling evidence that high levels of social anxiety are associated with atypical threat conditioning or extinction. Further, when systematically examining the data, there was no convincing support that the use of a particular psychophysiological measure, subjective rating, or experimental parameter yields more consistent associations between social anxiety and conditioning processes during threat acquisition or extinction. Meta-analyses demonstrated that during threat extinction, the use of anxiety ratings as a dependent variable, socially relevant unconditioned stimuli, and a higher reinforcement schedule produced more detectable effects of social anxiety on compromised extinction processes compared to any other dependent variable (subjective or physiological) or experimental parameter. Overall, the results of this study suggest that social anxiety is not reliably related to deficits in conditioning and extinction processes in the context of laboratory-based Pavlovian conditioning paradigms.
Wake et al. (2024) The effect of social anxiety on threat acquisition and extinction: a systematic review and meta-analysis. PeerJ 12:e17262 https://doi.org/10.7717/peerj.17262
Successful treatment of diplopia using prism correction combined with vision therapy/orthoptics improves health-related quality of life
Background To track improvement in diplopia symptoms with strabismus-specific health-related quality of life (HRQOL) questionnaire across a treatment consisting of prism correction followed by vision therapy/orthoptics when prism treatment alone has not succeeded. Methods Forty-eight participants with diplopia and a mean age of 62.45 were asked to complete an Adult Strabismus-20 (AS-20) questionnaire and a Diplopia Questionnaire (DQ) before and after prism correction. Inclusion criteria were diplopia reported on the DQ as “sometimes”, “often” or “always” at reading or straight-ahead distance. The prism correction was classified as successful if the participant reported “never” or “rarely” on the DQ for reading and straight-ahead distance; and unsuccessful if the perceived diplopia worsened or remained the same. For all participants, mean initial AS-20 scores were compared with mean post-prism correction scores, taking into account AS-20 subscales (reading and general functions, and self-perception and interaction). Participants in the failed prism treatment subgroup subsequently underwent a programme of vision therapy wearing their prism correction, the results of which were again determined by participants’ responses on the AS-20 questionnaire, completed before and after the vision therapy. Results Five of the 48 participants dropped out of the study. Prism correction was classified as successful in 22 of 43 participants (51%), and unsuccessful in 21 (49%). Those participants for whom the prism correction was classified as a success showed a statistically significant improvement (p = 0.01) in both reading and general functions. In the failed treatment subgroup, no significant change in AS-20 score was recorded for any of the domains (p = 0.1). After treatment with vision therapy/orthoptics, however, 13 of the 20 participants in the unsuccessful prism correction subgroup (one of them dropped out the study) achieved binocular vision and statistically significant improvement in reading and general functions (p = 0.01). Conclusions Although effective prism correction of diplopia is correlated with enhanced HRQOL, prism correction alone is frequently not sufficient to achieve this objective. In these cases, vision therapy/orthoptics treatment as a coadjutant to prism correction is shown to improve HRQOL.
Portela-Camino et al. (2024) Successful treatment of diplopia using prism correction combined with vision therapy/orthoptics improves health-related quality of life. PeerJ 12:e17315 https://doi.org/10.7717/peerj.17315