Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Integrating subvolume dose and myocardial perfusion imaging parameters to assess the impact of radiation therapy on heart function in breast cancer patients: A comparative analysis between left- and right-sided breast cancer.

BACKGROUND: This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. METHODS: Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. RESULTS: Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. CONCLUSION: This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.

Evaluation of the cardiac subvolume dose and myocardial perfusion in left breast cancer patients with postoperative radiotherapy: a prospective study.

Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region.Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https://clinicaltrials.gov/ct2/show/NCT01758419?cond=NCT01758419&draw=2&rank=1 .

IGF2BP2 promotes colorectal cancer progression by upregulating the expression of TFRC and enhancing iron metabolism.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.

[A Correlational Study of Leadership Styles and Nurses' Morale and Intention to Stay].

BACKGROUND: The leadership style of head nurses affects the organizational atmosphere of nursing teams. PURPOSE: The aim of this study was to analyze the correlation between head nurse leadership styles and nurses' morale and intention to stay, as well as the explained variance for each. METHODS: The descriptive correlational design employed in this study used a convenience sample of 790 nursing staff working at a medical center in southern Taiwan. We cross-sectionally surveyed each participant's intention to stay, morale, and perception of their head nurse's leadership style. RESULTS: The participants perceived their head nurses as having both transformational and transactional leadership styles. A moderate to highly positive correlation was identified among leadership style, morale, and intention to stay. One-way analyses of variance found that the participants who were seniors, were married, had children, were at clinical ladder N3 or above, had rotation experience, and held a public servant position had relatively higher morale and intention to stay. After controlling for potentially confounding factors, hierarchical regression analyses revealed that the explained variance of leadership styles on intention to stay and morale was 22% and 28%, respectively. Transformational leadership was found to significantly predict intention to stay and morale. However, transactional leadership significantly impacted morale only, albeit at a lower level than transformational leadership. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: How nurses perceive the leadership style of their head nurses may affect their intention to stay and morale while at work. Advanced training to strengthen and internalize leadership styles for head nurses is suggested. Creating a positive and friendly working environment is conducive to improving the morale of nurses and retention rates in the nursing workplace.

Effects of Exercise on Sleep Quality in Pregnant Women: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: Sleep quality was considered a priority concern facing pregnant women. Conventional wisdom argues that good sleep quality benefits pregnant women and their fetuses. The aim of this study is to assess the effects of a specific exercise program on the　sleep quality in pregnant women. METHODS: Searches were executed in seven databases since their inceptions until February 28, 2019, for randomized controlled trials evaluating the effects of an exercise program on the sleep quality and insomnia in pregnant women. A random-effects model was applied for meta-analysis, and odds ratio, mean differences (MDs), and 95% confidence intervals (CIs) are shown as parts of outcomes. RESULTS: Seven studies were included for meta-analysis. Compared with their not-exercising counterparts, analyses showed that regularly exercising women had significantly enhanced sleep quality, with an odds ratio of 6.21 (95% CI, 2.02-19.11;p = .001; I2 = 80.2%), with a standardized MD of -0.93 (95% CI, -1.19 to -0.67; p < .001; I2 = 30.0%). However, exercising women showed no significant insomnia improvement, with an standardized MD of -2.85 (95% CI, -7.67 to 1.98; p = .250; I2 = 97.0%), relative to their not-exercising counterparts. CONCLUSION: This research indicated that exercise has a positive impact on the sleep quality of pregnant women. Despite the aforementioned positive impact on sleep quality, the present study did not find evidence to support that exercise may also improve insomnia for pregnant women.

Transcriptome Based System Biology Exploration Reveals Homogeneous Tumorigenicity of Alimentary Tract Malignancy.

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs). There were 12 mRNAs, 5 miRNAs, and 16 lncRNAs in the core competitive endogenous RNAs network by RNA-RNA interactions, highlighting the prognostic nodes of SERPINE1, hsa-mir-145, and SNHG1. In addition, the weighted gene co-expression network analysis (WGCNA) illustrated 20 gene modules associated with clinical traits. By taking intersections of modules related to the same trait, we got 67 common genes shared by ESCA and READ and screened 5 hub genes, including ADCY6, CXCL3, NPBWR1, TAS2R38, and PTGDR2. In conclusion, the present study found that SERPINE1/has-mir-145/SNHG1 axis acted as promising targets and the hub genes reasoned the similarity between ESCA and READ, which revealed the homogeneous tumorigenicity of digestive tract cancers at the transcriptome level and led to further comprehension and therapeutics for digestive tract cancers.

Recombinant DNA vaccine of Hantavirus Gn and LAMP1 induced long-term immune protection in mice.

BACKGROUND: Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations. METHODS & RESULTS: Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay. HTNV-challenge assay identified long-term protection. Safety was confirmed by histological and behavioral analysis. Epitope-spreading phenomenon was noted, revealing two sets of dominant T-cell epitopes cross-species. CONCLUSION: pVAX-LAMP/Gn established memory responses within a long-term protection. Lysosome-targeted strategy showed promise on Gn-based DNA vaccine and further investigations are warranted in other immunogenic Hantaviral antigens.

Candida albicans Dbf4-dependent Cdc7 kinase plays a novel role in the inhibition of hyphal development.

Candida albicans is an opportunistic human fungal pathogen. The ability to switch among multiple cellular forms is key to its pathogenesis. The Dbf4-dependent protein kinase gene CDC7 is conserved due to its role in initiating DNA replication. Because a C. albicans Cdc7 (Cacdc7) homozygous null was not viable, we generated a C. albicans strain with a deleted C. albicans CDC7 (CaCDC7) allele and an expression-repressible allele. Surprisingly, cells of the strain grew as hyphae under the repressed conditions. The in vitro kinase assays confirmed that CaCdc7 (K232) and CaCdc7 (T437) are critical for catalytic and phosphoacceptor of activation activity, respectively. C. albicans cells formed hyphae when expressing either the catalytically inactive CaCdc7 (K232R) or the phosphoacceptor-deficient CaCdc7 (T437A). While CaCdc7 interacted with CaDbf4, cells of the strain in which CaCDC7 was repressed were not rescued by constitutively expressing C. albicans DBF4 or vice versa. We conclude that CaDBF4-dependent CaCDC7 is an essential gene suppressing the hyphal development.

The forkhead transcription factor FOXO1 stimulates the expression of the adipocyte resistin gene.

Resistin is known as an adipocyte-specific hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by transcriptional factors, but the possible role of forkhead transcription factor FOXO1 in regulating resistin gene expression is still unknown. Using 3T3 fibroblast and C3H10T1/2 and 3T3-L1 adipocytes, we found that transient overexpression of a non-phosphorylatable, constitutively active FOXO1, but not the wild type of FOXO1 or a DNA binding-deficient FOXO1, activated resistin promoter-directed luciferase expression. However, transient overexpression of a dominant-negative FOXO1 inactivated resistin promoter activity and reduced resistin mRNA expression. These observations indicate that the action of FOXO1 on resistin gene expression requires the activation of FOXO1 and that the effect of FOXO1 depends on the phosphorylation and dephosphorylation of FOXO1. The FOXO1 protein target sites on the resistin promoter were localized to the proximal -3545 to -787bp of 5'-flanking region of the resistin promoter. A chromatin immunoprecipitation assay also showed that FOXO1 bound the resistin promoter at nucleotide regions of -1539 to -1366bp and -1016 to -835bp, but not at the regions of -795 to -632bp. Results of this study suggest that FOXO1 transcription factor likely activates the expression of adipocyte resistin gene via direct association with the upstream resistin promoter.