Nonlinear relationship between circulating natural killer cell count and 1-year relapse rates in myasthenia gravis: a retrospective cohort study
Background The relapse rate in myasthenia gravis (MG) is high, and promising therapies have emerged; however, identifying potential predictive factors for relapse remains a challenge. This study aimed to explore the association between circulating natural killer (NK) cell levels and the risk of recurrence in MG. Methods This retrospective cohort study included 265 patients with MG whose data were included in the Neurology Department of the Affiliated Hospital of Guizhou Medical University database between March 2015 and March 2022. Data from electronic medical records were collected, which included the patients’ circulating NK cell count (exposure variable) and demographic/clinical characteristics (covariates). The primary outcome was the 1-year MG recurrence rate. Results The study revealed a non-linear relationship between peripheral NK cell count and MG recurrence, with an inflection point at 5.38. Below this threshold, the risk of recurrence was low with higher NK cell counts (relative risk (RR): 0.23, 95% confidence interval (CI) [0.11–0.490]); above this threshold, no significant association was observed (RR: 1.43, 95% CI [0.62–3.34]). Furthermore, the NK cell proportion showed no significant linear or non-linear association with MG recurrence risk (RR: 0.84, 95% CI [0.57–1.2]). Conclusion This study provides epidemiological evidence of a potential association between peripheral NK cell count and MG recurrence risk, suggesting an immunoregulatory protective effect within a specific NK cell count range. These findings may inform more personalized MG treatment strategies, warranting further validation in larger and more diverse cohorts.
Zhang et al. (2024) Nonlinear relationship between circulating natural killer cell count and 1-year relapse rates in myasthenia gravis: a retrospective cohort study. PeerJ 12:e18562 https://doi.org/10.7717/peerj.18562
Evidence of prostate cancer-linked virus zoonoses from biophysical genomic variations
An ongoing double-blind examination of (mathematically) smooth functional dependences of population-based genomic distributions of single nucleotide polymorphisms (SNPs) on quantified environmental parameters has flagged a SNP that has been associated with prostate cancer for dependence on zoonotic viruses. The SNP rs13091518 is an intergenic variant near the gene/pseudo-gene COX6CP6 on chromosome 3. The risk T allele, which is the major allele in all homeostatic populations considered, clearly demonstrates a negative adaptive force of about −0.1 universal genomic energy units/zoonotic virus unit. This biophysical perspective has thus provided evidence for a causative relationship between zoonotic viruses and prostate cancer. Our findings are consistent with other studies that have found an association between several zoonotic viruses and prostate cancer. This result demonstrates the significance of an intergenic variant in the adaptive response to a viral zoonotic pathogen.
Alsufyani et al. (2024) Evidence of prostate cancer-linked virus zoonoses from biophysical genomic variations. PeerJ 12:e18583 https://doi.org/10.7717/peerj.18583
Upregulation of HPV16E1 and E7 expression and FOXO3a mRNA downregulation in high-grade cervical neoplasia
Background Cervical cancer remains a significant global health concern, ranking as the fourth most prevalent cancer among women worldwide. Human papillomaviruses (HPV) transcribe many genes that might be responsible for cervical cancer development. This study aims to investigate the correlation between the expression of HPV16 early genes and the mRNA expression of human FOXO3a, a tumor suppressor gene, in association with various stages of cervical precancerous lesions. Methods Eighty-five positive HPV16 DNA cervical swab samples were recruited and categorized based on cytology stages, i.e., negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL). RT-qPCR was performed to amplify HPV16E1, E4, E6, E6*I, E7, and human FOXO3a mRNA expression in all samples. The relative expression of those genes was calculated using GAPDH as a control. Detection of FOXO3a mRNA expression in the cervical cancer cell line by RT-qPCR and meta-analysis of FOXO3a expression using the RNA-Seq dataset by GEPIA2 were analyzed to support the conclusions. Results Among the cervical samples, HPV16E1 and E7 were significantly increased expression correlating to disease severity. HPV16E4 mRNA expression was 100% detected in all LSIL samples, with a significant increase observed from normal to LSIL stages. Conversely, FOXO3a mRNA expression decreased with disease severity, and the lowest expression was observed in HSIL/squamous cell carcinoma (SCC) samples. In addition, similar results of FOXO3a downregulation were also found in the cervical cancer cell line and RNA-Seq dataset of cervical cancer samples. Conclusion HPV16 early mRNA levels, including E1 and E7, increase during cancer progression, and downregulation of FOXO3a mRNA is a characteristic of cervical cancer cells and HSIL/SCC. Additionally, HPV16E4 mRNA expression was consistently detected in all LSIL samples, suggesting the presence of active viral replication. These findings might lead to further investigation into the interplay between HPV gene expression and host cell factors for targeted therapeutic strategies in cervical cancer management.
Sasivimolrattana et al. (2024) Upregulation of HPV16E1 and E7 expression and FOXO3a mRNA downregulation in high-grade cervical neoplasia. PeerJ 12:e18601 https://doi.org/10.7717/peerj.18601
Health status and morphometrics of Galápagos magnificent frigatebirds (Fregata magnificens magnificens) determined by hematology, biochemistry, blood gas, and physical examination
The magnificent frigatebird (Fregata magnificens; MFB) is a widely distributed seabird. It has breeding areas in the tropical Atlantic Ocean and the Pacific Ocean (extending along Central America up to Baja California) (Schreiber & Burger, 2001). The Fregata magnificens magnificens (MFB-Gal) subspecies is native to the Galápagos Islands. This is the first-time hematology and blood chemistry parameters have been published for the F. m. magnificens (MFB-Gal) from the Galápagos Islands. Analysis was run on blood samples drawn from n = 16 adult MFB-Gal captured by hand at their nests at North Seymour and Daphne Major Islands in the Galápagos Islands (n = 10 MFB-Gal in June 2017 and n = 6 MFB-Gal in July 2022). There were ten female birds and six male birds in total. A portable blood analyzer (iSTAT) was used to obtain near immediate field results for total carbon dioxide (TCO2), hematocrit (Hct), hemoglobin (Hb), sodium (Na), potassium (K), chloride (Cl), ionized calcium (iCa), total protein (TP), anion gap and glucose. Blood lactate was measured using a portable Lactate Plus™ analyzer. Average heart rate, respiratory rate, body weight, body temperature, biochemistry and hematology parameters were comparable to healthy individuals of other Fregatidae of the same species (magnificent frigatebird subspecies from Brazil, Fregata magnificens, likely F. m. rothschildi) or similar species (great frigatebird, Fregata minor, from the Galápagos Islands). There were some statistically significant differences between the males and females F. m. magnificens (MFB-Gal) in the Galápagos, including bill depth, bill width, wing length, weight, and chloride blood value. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galápagos magnificent frigatebirds and other populations of magnificent frigatebirds.
Guzmán et al. (2024) Health status and morphometrics of Galápagos magnificent frigatebirds (Fregata magnificens magnificens) determined by hematology, biochemistry, blood gas, and physical examination. PeerJ 12:e18609 https://doi.org/10.7717/peerj.18609
The use of phosphate rock and plant growth promoting microorganisms for the management of Urochloa decumbens (Stapf.) R.D. Webster in acidic soils
Background Forage production in tropical soils is primarily limited by nutrient deficiencies, especially nitrogen (N) and phosphorus (P). The use of phosphate rock by plants is limited by its low and slow P availability and microbial phosphate solubilization is the main mechanism for P bioavailability in the soil-root system. The objectives of this study were (i) select a nitrogen-fixing bacteria which could be used as a co-inoculant with the Penicillium rugulosum IR94MF1 phosphate-solubilizing fungus and (ii) evaluate under field conditions the effect of inoculation combined with phosphate rock (PR) application on yield and nutrient absorption of a Urochloa decumbens pasture which was previously established in a low-fertility, acidic soil. Methods Various laboratory and greenhouse tests allowed for the selection of Enterobacter cloacae C17 as the co-inoculant bacteria with the IR94MF1 fungus. Later, under field conditions, a factorial, completely randomized block design was used to evaluate the inoculation with the IR94MF1 fungus, the IR94MF1+C17 co-inoculation, and a non-inoculated control. Two levels of fertilization with PR treatment (0 kg/ha and 200 kg/ha P2O5) were applied to each. Results During five consecutive harvests it was observed that the addition of biofertilizers significantly increased (p < 0.05) the herbage mass and N and P assimilation compared to the non-inoculated control. However, no statistically significant differences were observed for the PR application as P source. Conclusion P. rugulosum IR94MF1 is capable of solubilizing and accumulating P from the phosphate rock, making it available for plants growing in acid soils with low N content. These inoculants represent a good option as biofertilizers for tropical grasses already established in acidic soils with low N content.
Barbosa et al. (2024) The use of phosphate rock and plant growth promoting microorganisms for the management of Urochloa decumbens (Stapf.) R.D. Webster in acidic soils. PeerJ 12:e18610 https://doi.org/10.7717/peerj.18610
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