247 research outputs found
Family and Individual Risk and Protective Factors of Depression among Chinese Migrant Children with Oppositional Defiant Disorder Symptoms
Migrant children reached 35.81 million in China and were vulnerable to serious emotional problems including depression. The present study aimed to identify the family and individual risk and protective factors for depression in an at-risk sample of Chinese migrant children. Participants were 368 children (9.47 ± 1.46 years old, 73.4% boys) who had at least one symptom of Oppositional Defiant Disorder symptoms (ODD) and their parents in Mainland China. Risk and protective factors within both family (i.e., family maltreatment and family functioning) and individual (i.e., automatic thoughts and resilience) perspectives. Family maltreatment and negative automatic thoughts served as risk factors in relation to children's depression. Further, automatic thoughts mediated the relationship between family maltreatment and children's depression. Family functioning (cohesion, but bot adaptability) and individual resilience could buffer the effects of risk factors in the Structure Emotion Model such that both cohesion and resilience moderated the relationship between family maltreatment and children's automatic thoughts only. Our findings highlighted the urgent need to decrease risk factors and increase protective factors of both family and child individual characteristics in prevention and intervention depression among migrant children with ODD symptoms in China
Social Preference Deficits in Juvenile Zebrafish Induced by Early Chronic Exposure to Sodium Valproate
Prenatal exposure to sodium valproate (VPA), a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 hours post-fertilization (hpf) were treated with early chronic exposure to 20 μM VPA for 7 hours per day for 6 days or with early acute exposure to 100 μM VPA for 7 hours. A battery of behavioral screenings was conducted at 1 month of age to investigate social preference, locomotor activity, anxiety and behavioral response to light change. A social preference deficit was only observed in animals with chronic VPA exposure. Acute VPA exposure induced a change in the locomotor activity, while chronic VPA exposure did not affect locomotor activity. Neither exposure procedure influenced anxiety or the behavioral response to light change. These results suggested that VPA has the potential to affect some behaviors in zebrafish, such as social behavior and the locomotor activity, and that the effects were closely related to the concentration and the exposure window. Additionally, social preference seemed to be independent from other simple behaviors
Fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner
Microbes live mostly in a social community rather than in a planktonic state. Such communities have complex spatiotemporal patterns that require intercellular communication to coordinate gene expression. Here, we demonstrate that Cryptococcus neoformans, a model eukaryotic pathogen, responds to an extracellular signal in constructing its colony morphology. The signal that directs this community behavior is not a molecule of low molecular weight like pheromones or quorum-sensing molecules but a secreted protein. Znf2, a master regulator of morphogenesis in Cryptococcus, is necessary and sufficient for the production of this signal protein. Cfl1, a prominent Znf2-downstream adhesion protein (adhesin), was identified to be responsible for the paracrine communication. Consistent with its role in communication, Cfl1 is highly induced during mating colony differentiation, and some of the Cfl1 proteins undergo shedding and are released from the cell wall. The released Cfl1 is enriched in the extracellular matrix and acts as an autoinduction signal to stimulate neighboring cells to phenocopy Cfl1-expressing cells via the filamentation-signaling pathway. We further demonstrate the importance of an unannotated and yet conserved domain in Cfl1’s signaling activity. Although adhesion proteins have long been considered to be mediators of microbial pathogenicity and the structural components of biofilms, our work presented here provides the direct evidence supporting the signaling activation by microbial adhesion/matrix proteins
Laser Irradiation-Induced DNA Methylation Changes Are Heritable and Accompanied with Transpositional Activation of mPing in Rice
Enhancive effects of Lewis y antigen on CD44-mediated adhesion and spreading of human ovarian cancer cell line RMG-I
<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the molecular structural relationship between cell adhesive molecule CD44 and Lewis y antigen, and determine the effects of Lewis y antigen on CD44-mediated adhesion and spreading of ovarian cancer cell line RMG-I and the Lewis y antigen-overexpressed cell line RMG-I-H.</p> <p>Methods</p> <p>The expression of CD44 in RMG-I and RMG-I-H cells before and after treatment of Lewis y monoclonal antibody was detected by immunocytochemistry; the expression of Lewis y antigen and CD44 was detected by Western Blot. The structural relationship between Lewis y antigen and CD44 was determined by immunoprecipitation and confocal laser scanning microscopy. The adhesion and spreading of RMG-I and RMG-I-H cells on hyaluronic acid (HA) were observed. The expression of CD44 mRNA in RMG-I and RMG-I-H cells was detected by real-time RT-PCR.</p> <p>Results</p> <p>Immunocytochemistry revealed that the expression of CD44 was significantly higher in RMG-I-H cells than in RMG-I cells (<it>P </it>< 0.01), and its expression in both cell lines was significantly decreased after treatment of Lewis y monoclonal antibody (both <it>P </it>< 0.01). Western Blot confirmed that the content of CD44 in RMG-I-H cells was 1.46 times of that in RMG-I cells. The co-location of Lewis y antigen and CD44 was confirmed by co-immunoprecipitation. The co-expression of CD44 and Lewis y antigen in RMG-I-H cells was 2.24 times of that in RMG-I cells. The adhesion and spreading of RMG-I-H cells on HA were significantly enhanced as compared to those of RMG-I cells (<it>P </it>< 0.01), and this enhancement was inhibited by Lewis y monoclonal antibody (<it>P </it>< 0.01). The mRNA level of CD44 in both cell lines was similar (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Lewis y antigen strengthens CD44-mediated adhesion and spreading of ovarian cancer cells.</p
Study of prevalence and risk factors of chemotherapy-induced mucositis in gastrointestinal cancer using machine learning models
ObjectiveChemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population.MethodsTo achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed.ResultsThe study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026).ConclusionIn conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies
DNA methylation repatterning accompanying hybridization, whole genome doubling and homoeolog exchange in nascent segmental rice allotetraploids
Allopolyploidization, which entails interspecific hybridization and whole genome duplication (WGD), is associated with emergent genetic and epigenetic instabilities that are thought to contribute to adaptation and evolution. One frequent genomic consequence of nascent allopolyploidization is homoeologous exchange (HE), which arises from compromised meiotic fidelity and generates genetically and phenotypically variable progenies.
Here, we used a genetically tractable synthetic rice segmental allotetraploid system to interrogate genome‐wide DNA methylation and gene expression responses and outcomes to the separate and combined effects of hybridization, WGD and HEs.
Progenies of the tetraploid rice were genomically diverse due to genome‐wide HEs that affected all chromosomes, yet they exhibited overall methylome stability. Nonetheless, regional variation of cytosine methylation states was widespread in the tetraploids. Transcriptome profiling revealed genome‐wide alteration of gene expression, which at least in part associates with changes in DNA methylation. Intriguingly, changes of DNA methylation and gene expression could be decoupled from hybridity and sustained and amplified by HEs.
Our results suggest that HEs, a prominent genetic consequence of nascent allopolyploidy, can exacerbate, diversify and perpetuate the effects of allopolyploidization on epigenetic and gene expression variation, and hence may contribute to allopolyploid evolution
Hyponatremia in Children With Bacterial Meningitis
Background: Hyponatremia has frequently been described as a common complication associated with bacterial meningitis, though its frequency and clinical course in children with bacterial meningitis are unclear. The present study aimed to investigate the frequency, clinical characteristics, and prognosis associated with pediatric hyponatremia due to bacterial meningitis.Methods: We performed a retrospective review of children with bacterial meningitis provided with standard care. One hundred seventy-five children were included. We documented all participants' symptoms and signs, laboratory and microbiological data, radiological findings, and complications that occurred during their hospital admission. Disease severity was determined using the maximum Pediatric Cerebral Performance Category (PCPC) and minimum Glasgow Coma Scale (GCS). Residual deficits were assessed using PCPC at discharge.Results: Hyponatremia (<135 mmol/L) was seen in 116 (66.4%) of the patients assessed and was classified as mild (130–135 mmol/L) in 77, moderate (125–129 mmol/L) in 26, and severe (<125 mmol/L) in 13. Hyponatremia was associated with a shorter duration of symptoms before admission, higher CSF white cell counts, and a longer duration of hospitalization. Moderate and severe hyponatremia were associated with an increase in convulsions, impaired consciousness, altered CSF protein levels, higher maximum PCPC scores, and lower minimum GCS scores. Severe hyponatremia was further associated with the development of systemic complications including shock, multiple organ dysfunction syndrome, respiratory failure requiring mechanical ventilation, and an increase in poor outcome (PCPC ≥ 2). Hyponatremia was not associated with the development of neurologic complications. Logistic regression analyses revealed that convulsions (OR 12.09, 95% CI 2.63–56.84) and blood glucose levels > 6.1 mmol/L (OR 8.28, 95% CI 1.65–41.60) predicted severe hyponatremia.Conclusion: Hyponatremia occurred in 66.4% of the assessed pediatric bacterial meningitis patients. Moderate and severe hyponatremia affected the severity of pediatric bacterial meningitis. Only severe hyponatremia affected the short-term prognosis of patients with pediatric bacterial meningitis. We recommend that patients with pediatric bacterial meningitis who exhibit convulsions and increased blood glucose levels should be checked for severe hyponatremia. Further studies are needed to evaluate the effectiveness of treatment of hyponatremia
Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression
Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation
Apolipoprotein E Overexpression Is Associated With Tumor Progression and Poor Survival in Colorectal Cancer
Apolipoprotein E (ApoE) plays a key role in tumorigenesis and progression, such as cell proliferation, angiogenesis and metastasis. ApoE overexpression was associated with aggressive biological behaviors and poor prognosis in a variety of tumor according to previous studies. This study aimed to assess the prognostic value and explore the potential relationship with tumor progression in colorectal cancer (CRC). We collected the expression profiling microarray data from the Gene Expression Omnibus (GEO), investigated the ApoE expression pattern between the primary CRC and liver metastasis of CRC, and then explored the gene with prognostic significance based on the TCGA database. ApoE high expression was associated with poor overall survival (OS, p = 0.015) and progression-free survival (PFS, p = 0.004) based on the public databases. Next, ApoE expression was evaluated in two CRC cohorts by immunohistochemistry, of whom 306 cases were stage II and 201 cases were metastatic liver CRC. In the cohort of the liver metastasis, the ApoE expression was increasing in normal mucosa tissue, primary colorectal cancer (PC), and colorectal liver metastases (CLM) in order. Meanwhile, the level of ApoE expression in stage II tumor sample which had no progression evidence in 5 years was lower than that in PC of synchronous liver metastases. The high ApoE expression in PC was an independent risk factor in both stage II (HR = 2.023, [95% CI 1.297–3.154], p = 0.002; HR = 1.883, [95% CI 1.295-2.737], p = 0.001; OS and PFS respectively) and simultaneous liver metastasis (HR = 1.559, [95% CI 1.096–2.216], p = 0.013; HR = 1.541, [95% CI 1.129–2.104], p = 0.006; OS and PFS respectively). However, the overexpression of ApoE could not predict the benefit from the chemotherapy in stage II. The study revealed that the relevance of the ApoE overexpression in CRC progression, conferring a poor prognosis in CRC patients especially for stage II and simultaneous liver metastasis. These finding may improve the prognostic stratification of patients for clinical strategy selection and promote CRC clinic outcomes
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