In vitro culture of leukemic cells in collagen scaffolds and carboxymethyl cellulose-polyethylene glycol gel
Background Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the accumulation of neoplastic mature B cells in blood, bone marrow, lymph nodes, and spleen. The disease biology remains unresolved in many aspects, including the processes underlying the disease progression and relapses. However, studying CLL in vitro poses a considerable challenge due to its complexity and dependency on the microenvironment. Several approaches are utilized to overcome this issue, such as co-culture of CLL cells with other cell types, supplementing culture media with growth factors, or setting up a three-dimensional (3D) culture. Previous studies have shown that 3D cultures, compared to conventional ones, can lead to enhanced cell survival and altered gene expression. 3D cultures can also give valuable information while testing treatment response in vitro since they mimic the cell spatial organization more accurately than conventional culture. Methods In our study, we investigated the behavior of CLL cells in two types of material: (i) solid porous collagen scaffolds and (ii) gel composed of carboxymethyl cellulose and polyethylene glycol (CMC-PEG). We studied CLL cells’ distribution, morphology, and viability in these materials by a transmitted-light and confocal microscopy. We also measured the metabolic activity of cultured cells. Additionally, the expression levels of MYC, VCAM1, MCL1, CXCR4, and CCL4 genes in CLL cells were studied by qPCR to observe whether our novel culture approaches lead to increased adhesion, lower apoptotic rates, or activation of cell signaling in relation to the enhanced contact with co-cultured cells. Results Both materials were biocompatible, translucent, and permeable, as assessed by metabolic assays, cell staining, and microscopy. While collagen scaffolds featured easy manipulation, washability, transferability, and biodegradability, CMC-PEG was advantageous for its easy preparation process and low variability in the number of accommodated cells. Both materials promoted cell-to-cell and cell-to-matrix interactions due to the scaffold structure and generation of cell aggregates. The metabolic activity of CLL cells cultured in CMC-PEG gel was similar to or higher than in conventional culture. Compared to the conventional culture, there was (i) a lower expression of VCAM1 in both materials, (ii) a higher expression of CCL4 in collagen scaffolds, and (iii) a lower expression of CXCR4 and MCL1 (transcript variant 2) in collagen scaffolds, while it was higher in a CMC-PEG gel. Hence, culture in the material can suppress the expression of a pro-apoptotic gene (MCL1 in collagen scaffolds) or replicate certain gene expression patterns attributed to CLL cells in lymphoid organs (low CXCR4, high CCL4 in collagen scaffolds) or blood (high CXCR4 in CMC-PEG).
Svozilova et al. (2024) In vitro culture of leukemic cells in collagen scaffolds and carboxymethyl cellulose-polyethylene glycol gel. PeerJ 12:e18637 https://doi.org/10.7717/peerj.18637
The mediation role of sleep on the relationship between drinks behavior and female androgenetic alopecia
Objectives To investigate the relationship between drinks behavior and female androgenetic alopecia (AGA) and to clarify the mediating effect of sleep behavior on such relationship. Methods A total of 308 female AGA patients and 305 female normal controls were recruited from the hospital, and questionnaires including drinks behavior and sleep behavior were inquired among them. Blood sugar and blood lipids were detected. Then, the mediating effect of sleep behavior on the relationship between drinks behavior and AGA was analyzed. Results Female AGA patients presented a higher frequency of intake of sweetened tea drinks. It was found that occasional intake (1–2 times per week; ORadj = 2.130, 95% CI [1.495–3.033]) and frequent intake (3–6 time per week; ORadj = 2.054, 95% CI [1.015–4.157]) of sweetened tea drinks were associated with AGA. The daily sugar intake from soft drinks increased the risk of AGA (ORadj = 1.025, 95% CI [1.003–1.048]), and hyperglycemia was positively associated with alopecia (ORadj = 1.897, 95% CI [1.225–2.936]). In addition, bedtime after 12 pm significantly increased the risk of developing alopecia (ORadj = 2.609, 95% CI [1.020–6.676]). Interestingly, bedtime, instead of daily sugar intake from soft drinks, could mediate the relationship between sweetened tea drinks intake and alopecia. Conclusions Sweetened tea drinks consumption increases the risk of female AGA, which is mediated by bedtime.
Liu et al. (2024) The mediation role of sleep on the relationship between drinks behavior and female androgenetic alopecia. PeerJ 12:e18647 https://doi.org/10.7717/peerj.18647
Effects of combined immunosuppressant and hepatitis B virus antiviral use on COVID-19 vaccination in recipients of living donor liver transplantation
Background & Aims The global pandemic caused by the highly contagious SARS-CoV-2 virus led to the emergency approval of COVID-19 vaccines to reduce rising morbidity and mortality. However, limited research exists on evaluating the impact of these vaccines on immunocompromised individuals, such as recipients of living donor liver transplantation, highlighting the need for further studies to better understand their effectiveness in this specific population. Methods From June 2021, we followed up on the effectiveness of the vaccine for patients taking immunosuppressive drugs after living-donor liver transplantation (LDLT). A total of 105 immunocompromised individuals participated, of which 50 patients with hepatitis B were taking antiviral drugs. Patients were assessed to analyze how the combination of immunosuppressive and antiviral drugs affected the efficacy of the BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 COVID-19 vaccines. Results Before and after the vaccinations, patients were monitored to establish differences between immunosuppressed patients and those additionally taking antiviral drugs. In immunocompromised patients taking antiviral drugs for hepatitis B, we confirmed that the effect of the COVID-19 vaccine was reduced when compared to immunocompromised patients. Interestingly, 23 patients (11 without and 12 additionally with hepatitis B drug administration) encountered breakthrough infections, and although there was a minor discrepancy in vaccine efficacy among the patients taking antiviral drugs for hepatitis B, it did not reach statistical significance. Conclusions Additional COVID-19 vaccination is recommended for patients taking immunosuppressive drugs and hepatitis B antiviral drugs after LDLT.
Lee et al. (2024) Effects of combined immunosuppressant and hepatitis B virus antiviral use on COVID-19 vaccination in recipients of living donor liver transplantation. PeerJ 12:e18651 https://doi.org/10.7717/peerj.18651
The epigenetic role of EZH2 in acute myeloid leukemia
Acute myeloid leukemia (AML), a malignant disease of the bone marrow, is characterized by the clonal expansion of myeloid progenitor cells and a block in differentiation. The high heterogeneity of AML significantly impedes the development of effective treatment strategies. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), regulates the expression of downstream target genes through the trimethylation of lysine 27 on histone 3 (H3K27me3). Increasing evidence suggests that the dysregulation of EZH2 expression in various cancers is closely associated with tumorigenesis. In the review, we examine the role of EZH2 in AML, highlighting its crucial involvement in regulating stemness, proliferation, differentiation, immune response, drug resistance and recurrence. Furthermore, we summarize the application of EZH2 inhibitors in AML treatment and discuss their potential in combination with other therapeutic modalities. Therefore, targeting EZH2 may represent a novel and promising strategy for the treatment of AML.
Fang et al. (2024) The epigenetic role of EZH2 in acute myeloid leukemia. PeerJ 12:e18656 https://doi.org/10.7717/peerj.18656
The impact of nurses’ stress situation coping on somatization: a mediated moderation model
Aims The purpose of this study is to investigate the impact of nurses’ stress situation coping levels on somatization symptoms, the mediating effect of depression, and the moderating effect of perceived social support. Background As a core part of the global healthcare system, nurses are crucial to patient health and rehabilitation outcomes. However, due to heavy workloads, unreasonable staffing structures, and constant exposure to occupational risks in their workplaces, these factors often place nurses in a high-intensity, high-stress environment, which directly affects their physical and mental health and professional burnout. Coping with stress situations is an important means to help individuals effectively manage stress, reduce negative impacts, and maintain mental health. However, research on the impact of nurses’ stress situation coping methods on somatization symptoms is limited. Methods This study conducted a cross-sectional survey from December 2022 to April 2023, and finally included 293 nurses working on the front line of tertiary hospitals. Data was collected through questionnaires and analyzed using SPSS 24.0 and the SPSS macro program’s Models 7 and 14. This study is an observational study, strictly prepared and presented according to the STROBE checklist. Results The somatization symptom scores of the nurses were (27.27 ± 7.33) points, the stress situation coping scores were (59.90 ± 9.64) points, the perceived social support scores were (65.64 ± 12.90) points, and the depression scores were (4.42 ± 4.12) points. The somatization symptom scores of the nurses were positively correlated with the stress situation coping scores and depression scores, and negatively correlated with the perceived social support scores, with correlation coefficients of 0.200, 0.851, and −0.302, respectively. The stress coping level of the nurses had a direct positive impact on somatization symptoms (β = 0.081, p = 0.009), and a direct positive impact on nurse depression (β = 0.202, p = 0.001). Depression had a significant positive impact on somatization symptoms (β = 0.823, p = 0.000), and depression played a mediating role. Perceived social support had a significant negative impact on depression (β = −0.383, p = 0.000). Perceived social support had a significant moderating effect on the relationship between the stress situation coping level and depression (β = −0.121, p = 0.003). Conclusion In this study, the stress situation coping methods of nurses had a positive impact on somatization symptoms, had a complete mediating effect on the depression level of nurses, and perceived social support had a significant moderating effect in the pathway from the stress situation coping methods of nurses to depression-mediated somatization symptoms.
Qi et al. (2024) The impact of nurses’ stress situation coping on somatization: a mediated moderation model. PeerJ 12:e18658 https://doi.org/10.7717/peerj.18658
Taurine stimulation of planarian motility: a role for the dopamine receptor pathway
Taurine, a normal dietary component that is found in many tissues, is considered important for a number of physiological processes. It is thought to play a particular role in eye development and in the maturation of both the muscular and nervous systems, leading to its suggested use as a therapeutic for Alzheimer’s and Parkinson’s diseases. Taurine increases metabolism and has also been touted as a weight loss aid. Due to its possible benefits to health and development, taurine is added as a supplement to a wide array of products, including infant formula and energy drinks. Despite its pervasive use as a nutritional additive and implied physiological actions, there is little consensus on how taurine functions. This is likely because, mechanistically, taurine has been demonstrated to affect multiple metabolic pathways. Simple models and straightforward assay systems are required to make headway in understanding this complexity. We chose to begin this work using the planarian because these animals have basic, well-understood muscular and nervous systems and are the subjects of many well-tested assays examining how their physiology is influenced by exposure to various environmental, nutritional, and therapeutic agents. We used a simple behavioral assay, the planarian locomotor velocity test (pLmV), to gain insight into the stimulant properties of taurine. Using this assay, we observed that taurine is a mild stimulant that is not affected by sugars or subject to withdrawal. We also provide evidence that taurine makes use of the dopamine D1 receptor to mediate this stimulant effect. Given the pervasiveness of taurine in many commercial products, our findings using the planarian system provide needed insight into the stimulant properties of taurine that should be considered when adding it to the diet.
Livengood et al. (2024) Taurine stimulation of planarian motility: a role for the dopamine receptor pathway. PeerJ 12:e18671 https://doi.org/10.7717/peerj.18671
Motor competence of children in Singapore using Movement ABC-2 test
Introduction The Movement Assessment Battery for Children, 2nd Edition (MABC-2) test is a valuable tool for identifying motor delays in children globally. However, there has been a lack of data for children in Singapore. Methods This study compared 175 children in Singapore (SG) aged 3–6 years to MABC-2 data based on the United Kingdom (UK) population, using statistical tests to analyze age, country, and gender effects on motor competence. Results The results showed a positive age effect across all tasks, with SG children excelling in balance but lagging in aiming and catching tasks compared to UK children. The interaction between age and country yielded mixed results, favoring different groups at various ages. Additionally, girls displayed better manual dexterity and static balance than boys. Conclusion Encouraging more physical activities, especially those involving object manipulation, is crucial for SG children. Establishing local norms for the MABC-2 in Singapore and considering country-specific factors in motor competence evaluations can enhance early intervention strategies. These findings emphasize the importance of tailored approaches to address motor skill development in SG children.
Tan et al. (2024) Motor competence of children in Singapore using Movement ABC-2 test. PeerJ 12:e18446 https://doi.org/10.7717/peerj.18446
Nonadjacent dependencies and sequential structure of chimpanzee action during a natural tool-use task
Many of the complex behaviours of humans involve the production of nonadjacent dependencies between sequence elements, which in part can be generated through the hierarchical organization of sequences. To understand how these structural properties of human behaviours evolved, we can gain valuable insight from studying the sequential behaviours of nonhuman animals. Among the behaviours of nonhuman apes, tool use has been hypothesised to be a domain of behaviour which likely involves hierarchical organization, and may therefore possess nonadjacent dependencies between sequential actions. However thus far, evidence supporting hierarchical organization of great-ape tool use comes from methodologies which have been criticised in their objectivity. Additionally, the extent to which nonadjacent dependencies appear in primate action sequences during tool use has not been formally investigated. We used estimations of mutual information (MI)—a measure of dependency strength between sequence elements—to evaluate both the extent to which wild chimpanzees produce nonadjacent dependencies during a naturalistic tool-use task (nut cracking), as well as how sequences of actions are likely organized during tool use. Half of adult chimpanzees produced nonadjacent dependencies at significantly greater sequential distances than comparable, nonhierarchical Markov models once repeated actions had been accounted for. Additionally, for the majority of chimpanzees, MI decay with increasing sequential distance included a power-law relationship, which is a key indicator that the action sequences produced by chimpanzees likely entail some degree of hierarchical organization. Our analysis offered the greatest support for a system of organization where short subroutines of actions (2–8 actions long) are hierarchically arranged into longer sequences—a finding which is consistent with previous qualitative descriptions of ape tool-use behaviours. Interindividual variability was detected within our analysis in both the maximum distance dependencies were detected, and the most likely structuring mechanism for sequential action organization. We discuss these results in light of possible interindividual variation in the systems of action organization used by chimpanzees during tool use, in addition to methodological considerations for applications of MI estimations to sequential behaviours. Moreover, we discuss our main findings alongside hypotheses for the coevolution of complex syntax in language and tool-action across hominin evolutionary history.
Howard-Spink et al. (2024) Nonadjacent dependencies and sequential structure of chimpanzee action during a natural tool-use task. PeerJ 12:e18484 https://doi.org/10.7717/peerj.18484
PhyIN: trimming alignments by phylogenetic incompatibilities among neighbouring sites
In phylogenomics, regions of low alignment reliability and high noise are typically trimmed from multiple sequence alignments before they are used in phylogenetic inference. I introduce a new trimming tool, PhyIN, which deletes regions in which a large proportion of sites (characters) have conflicting phylogenetic signal. It does not require inference of a phylogenetic tree, as it finds neighbouring characters that cannot agree on any possible tree. In phylogenomic data of ultraconserved elements (UCE), PhyIN effectively finds the boundaries between chaotic (conflicted) and orderly regions of alignments with data for only a single locus. Its ability to work on individual loci allows it to preserve discord between gene trees and species trees.
Maddison (2024) PhyIN: trimming alignments by phylogenetic incompatibilities among neighbouring sites. PeerJ 12:e18504 https://doi.org/10.7717/peerj.18504
CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms
CYP3A, a key member of the cytochrome P450 (CYP450) superfamily, is integral to drug metabolism, processing a substantial portion of medications. Their role in drug metabolism is particularly prominent, as CYP3A4 and CYP3A5 metabolize approximately 30–50% of known drugs. The genetic polymorphism of CYP3A4/5 is significant inter-individual variability in enzymatic activity, which can result in different pharmacokinetic profiles in response to the same drug among individuals. These polymorphisms can lead to either increased drug toxicity or reduced therapeutic effects, requiring dosage adjustments based on genetic profiles. Consequently, the study of the enzymatic activity of CYP3A4/5 gene variants is of great importance for the formulation of personalized treatment regimens. This article first reviews the role of CYP3A4/5 in drug metabolism in the human body, including inhibitors and inducers of CYP3A4/5 and drug-drug interactions. In terms of genetic polymorphism, it discusses the detection methods, enzymatic kinetic characteristics, and clinical guidelines for CYP3A5. Finally, the article summarizes the importance of CYP3A4/5 in clinical applications, including personalized therapy, management of drug-drug interactions, and adjustment of drug doses. This review contributes to the understanding of the functions and genetic characteristics of CYP3A4/5, allowing for more effective clinical outcomes through optimized drug therapy.
Zhang et al. (2024) CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms. PeerJ 12:e18636 https://doi.org/10.7717/peerj.18636