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1.
Signal Transduct Target Ther ; 9(1): 98, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609366

ABSTRACT

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (ß) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor ß. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Adult , Animals , Humans , Aged , SARS-CoV-2 , Receptor, Insulin , C-Peptide , DNA Helicases , Retrospective Studies , Poly-ADP-Ribose Binding Proteins , RNA Helicases , RNA Recognition Motif Proteins , Glucose
2.
Clin Nucl Med ; 49(6): 536-539, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38598512

ABSTRACT

PURPOSE: Chronic recurrent multifocal osteomyelitis (CRMO), or chronic nonbacterial osteomyelitis, is difficult to diagnose. The accurate diagnosis of CRMO relies on comprehensive imaging examinations because of its multifocal nature. In this regard, 18 F-FDG PET/CT has demonstrated significant utility in inflammatory diseases. This study tries to determine the value of FDG PET/CT in the evaluation of CRMO. PATIENTS AND METHODS: We retrospectively collected imaging data from pediatric CRMO patients who underwent FDG PET/CT scans. Lesions exhibiting abnormal metabolism with/without structural abnormalities on FDG PET/CT were identified as CRMO lesions, and their location and SUV max were recorded. RESULTS: A total of 21 pediatric patients with CRMO were included in this study. The median age at diagnosis was 9.4 years. Total 131 foci of abnormal activity were identified using FDG PET/CT imaging. The distribution pattern showed a higher prevalence of lower limbs and pelvis involvement. Among all identified lesions, abnormalities were detected on both PET and CT images of 93 lesions, whereas exclusively positive findings on 18 F-FDG PET alone were observed for 38 of them. CONCLUSIONS: Our study findings suggest a higher prevalence of lesions in the bones of the lower limbs and pelvis among children with CRMO. Compared with CT scans, FDG PET exhibits superior sensitivity in detecting these lesions.


Subject(s)
Fluorodeoxyglucose F18 , Osteomyelitis , Positron Emission Tomography Computed Tomography , Humans , Osteomyelitis/diagnostic imaging , Child , Female , Male , Adolescent , Child, Preschool , Retrospective Studies
3.
Cell Death Discov ; 10(1): 134, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472168

ABSTRACT

Endoplasmic reticulum (ER) stress can trigger various cell death mechanisms beyond apoptosis, providing promise in cancer treatment. Oncosis, characterized by cellular swelling and increased membrane permeability, represents a non-apoptotic form of cell death. In our study, we discovered that Arnicolide D (AD), a natural sesquiterpene lactone compound, induces ER stress-mediated oncosis in hepatocellular carcinoma (HCC) cells, and this process is reactive oxygen species (ROS)-dependent. Furthermore, we identified the activation of the PERK-eIF2α-ATF4-CHOP pathway during ER stress as a pivotal factor in AD-induced oncosis. Notably, the protein synthesis inhibitor cycloheximide (CHX) was found to effectively reverse AD-induced oncosis, suggesting ATF4 and CHOP may hold crucial roles in the induction of oncosis by AD. These proteins play a vital part in promoting protein synthesis during ER stress, ultimately leading to cell death. Subsequent studies, in where we individually or simultaneously knocked down ATF4 and CHOP in HCC cells, provided further confirmation of their indispensable roles in AD-induced oncosis. Moreover, additional animal experiments not only substantiated AD's ability to inhibit HCC tumor growth but also solidified the essential role of ER stress-mediated and ROS-dependent oncosis in AD's therapeutic potential. In summary, our research findings strongly indicate that AD holds promise as a therapeutic agent for HCC by its ability to induce oncosis.

4.
Clin Nucl Med ; 49(4): 371-372, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38350091

ABSTRACT

ABSTRACT: Coexistence of Langerhans cell histiocytosis and ganglioneuroblastoma is rare and seldom reported in the literature. A 3-year-old girl with Langerhans cell histiocytosis underwent 18 F-FDG PET/CT imaging for staging, which demonstrated significant 18 F-FDG accumulation in the mandibles. Unexpectedly, a mild hypermetabolic soft mass was detected in the upper retroperitoneum. Results of surgical pathology of the abdominal mass were consistent with ganglioneuroblastoma.


Subject(s)
Ganglioneuroblastoma , Histiocytosis, Langerhans-Cell , Female , Humans , Child , Child, Preschool , Fluorodeoxyglucose F18 , Ganglioneuroblastoma/complications , Ganglioneuroblastoma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/diagnostic imaging
5.
Clin Nucl Med ; 49(2): 198-200, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38015714

ABSTRACT

ABSTRACT: 123 I-MIBG SPECT/CT was performed for follow-up in an asymptomatic 8-year-old girl with a history of neuroblastoma. The images showed an unsuspected abnormal accumulation in the head, which was identified as a hyperdense lesion of the dura with increasing MIBG uptake, suggesting the possibility of metastasis from neuroblastoma. A brain MRI with contrast showed a remarkably enhanced lesion beside the confluence of sinuses, which mimicked meningioma. Results of the surgical pathology are consistent with the diagnosis of dural metastasis from neuroblastoma.


Subject(s)
3-Iodobenzylguanidine , Neuroblastoma , Female , Humans , Child , Single Photon Emission Computed Tomography Computed Tomography , Tomography, Emission-Computed, Single-Photon , Neuroblastoma/diagnostic imaging , Neuroblastoma/pathology
6.
Trauma Violence Abuse ; 25(1): 197-214, 2024 01.
Article in English | MEDLINE | ID: mdl-36704939

ABSTRACT

Children of color-especially Black and Indigenous children-are disproportionately overrepresented in foster care and experience barriers in accessing services and receiving physical and behavioral healthcare compared to their White counterparts. Although racial disparities in mental health outcomes of children in foster care have been examined systematically, less is known about racial disparities in their physical health outcomes. This systematic review aimed to examine disparities in physical health outcomes (i.e., general health, developmental delays and disability, chronic illness, health-compromising behaviors, all-cause mortality) of children in foster care by their race and ethnicity (PROSPERO ID: CRD42021272072). Systematic literature searches were conducted in PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Library, and Psychology and Behavioral Sciences Collection. Of the 6,102 unique studies identified, 24 met inclusion criteria: peer-reviewed journal article; published from 1991 to 2021; written in English; involved children in the U.S. foster care system; children were primarily in family-based placements; included health outcomes; included children's race and ethnicity; conducted quantitative analyses; and had an observational study design. There was limited evidence to suggest racial disparities among physical health domains examined, in part, due to the small number of studies, variability across study measures and designs, how race and ethnicity were categorized, and how related results were reported. Research that disaggregates results by more nuanced race and ethnicity categories, goes beyond including race and ethnicity as control variables, and uses more robust study designs to understand where racial disparities lie is necessary to inform practice and policy efforts to attain race and health equity in child welfare.


Subject(s)
Delivery of Health Care , Ethnicity , Child , Humans , Child Welfare , Research Design , Outcome Assessment, Health Care , Observational Studies as Topic
7.
World J Clin Oncol ; 14(10): 357-372, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37970111

ABSTRACT

BACKGROUND: Burkitt lymphoma (BL) is an exceptionally aggressive malignant neoplasm that arises from either the germinal center or post-germinal center B cells. Patients with BL often present with rapid tumor growth and require high-intensity multi-drug therapy combined with adequate intrathecal chemotherapy prophylaxis, however, a standard treatment program for BL has not yet been established. It is important to identify biomarkers for predicting the prognosis of BLs and discriminating patients who might benefit from the therapy. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To identify hub genes and perform gene ontology (GO) and survival analysis in BL. METHODS: Gene expression profiles and clinical traits of BL patients were collected from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was applied to construct gene co-expression modules, and the cytoHubba tool was used to find the hub genes. Then, the hub genes were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, a Protein-Protein Interaction network and a Genetic Interaction network were constructed. Prognostic candidate genes were identified through overall survival analysis. Finally, a nomogram was established to assess the predictive value of hub genes, and drug-gene interactions were also constructed. RESULTS: In this study, we obtained 8 modules through WGCNA analysis, and there was a significant correlation between the yellow module and age. Then we identified 10 hub genes (SRC, TLR4, CD40, STAT3, SELL, CXCL10, IL2RA, IL10RA, CCR7 and FCGR2B) by cytoHubba tool. Within these hubs, two genes were found to be associated with OS (CXCL10, P = 0.029 and IL2RA, P = 0.0066) by survival analysis. Additionally, we combined these two hub genes and age to build a nomogram. Moreover, the drugs related to IL2RA and CXCL10 might have a potential therapeutic role in relapsed and refractory BL. CONCLUSION: From WGCNA and survival analysis, we identified CXCL10 and IL2RA that might be prognostic markers for BL.

8.
Children (Basel) ; 10(10)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37892286

ABSTRACT

This study examined the associations of grandparent-grandchild relational closeness and conflict with grandchildren's socioemotional and behavioral problems, including emotional symptoms, conduct problems, hyperactivity, peer problems, and abnormal prosocial behaviors. We analyzed primary cross-sectional survey data collected from custodial grandparents in the United States using logistic regression models. The results indicated that grandparent-grandchild relational closeness was significantly associated with lower odds of custodial grandchildren having emotional symptoms, conduct problems, peer problems, and abnormal prosocial behaviors, whereas grandparent-grandchild relational conflict was significantly associated with higher odds of emotional symptoms, conduct problems, hyperactivity, peer problems, and abnormal prosocial behaviors. Implications for increasing grandparent-grandchild relational closeness and decreasing relational conflicts among grandparent-headed families are discussed, which might improve grandchildren's socioemotional and behavioral well-being.

9.
Front Psychol ; 14: 1238308, 2023.
Article in English | MEDLINE | ID: mdl-37809302

ABSTRACT

Background: Relative deprivation is one of the factors that influences the development of personality and behavior. However, it is still unclear whether and how relative deprivation decreases the prosocial behavior in adolescents. This study aimed to examine the association between relative deprivation and adolescent prosocial behavior and the role of emotion regulation strategies and empathy in modifying this association. Methods: The present study included 609 secondary school students (M = 15.42 years, SD = 0.653) in Fujian Province, China. All participants completed the Relative Deprivation Questionnaire, Emotion Regulation Scale, the Basic Empathy Scale, and Prosocial Behavior Scale. The collected data were analyzed using SPSS 25.0 and Mplus 7.4. Results: Relative deprivation was negatively correlated with cognitive reappraisal, but positively correlated with expressive suppression. Cognitive reappraisal was positively correlated with empathy and prosocial behavior, but expressive suppression was not. Empathy was positively correlated with prosocial behavior. Relative deprivation decreased prosocial behavior through (a) cognitive reappraisal, (b) empathy, and (c) chain mediation of cognitive reappraisal and empathy. No significant mediating effect of expressive suppression was found. Conclusion: The results indicate that relative deprivation decreases adolescent prosocial behavior, and that cognitive reappraisal and empathy are the potential psychological mechanisms that affect the association between relative deprivation and adolescent prosocial behavior.

10.
Article in English | MEDLINE | ID: mdl-37754629

ABSTRACT

This scoping review aimed to identify predisposing, enabling, and need factors associated with the use of mental health services, including psychotropic medications, among children in out-of-home care in the United States. We searched the PsycInfo, SocINDEX, Medline, and Scopus databases, and 22 studies met inclusion criteria and were systematically analyzed. Among the included studies, 7 studies examined predictors associated with taking psychotropic medications, and 16 examined factors associated with using other mental health services. Significant predisposing, enabling, and need factors associated with greater use of mental health services, including psychotropic medications, were identified. The most frequently identified predisposing factors were child race/ethnicity, age, gender, and maltreatment. Important enabling factors were out-of-home placement type and length of care, and need factors included children's mental/behavioral problems. The results provide insight into maximizing factors facilitating children's use of mental health services to address mental health problems of children in out-of-home care. Further, the results imply the importance of the appropriate use of psychotropic medication (e.g., the type and dosage of medications) among children in out-of-home care. The identified factors can inform child welfare agencies and stakeholders on ways to improve access to mental health services and the appropriate use of psychotropic medications among children in out-of-home care in the United States.


Subject(s)
Home Care Services , Mental Health Services , Humans , United States , Child , Psychotropic Drugs/therapeutic use , Child Protective Services , Databases, Factual
11.
Article in English | MEDLINE | ID: mdl-37691512

ABSTRACT

BACKGROUND: The pathogenesis of post-traumatic stress disorder (PTSD) triggered by high-voltage electrical burn (HVEB) remains unclear and the oxidative stress plays a role in this process. The purpose of this study is to investigate the underlying mechanism of oxidative stress mediates hippocampal neuronal apoptosis in rats with PTSD triggered by HVEB. MATERIALS AND METHODS: The PTSD rat model was developed by stimulating with high voltage electricity and screened using behavioral performance including Morris water maze (MWM), elevated plus-maze (EPM) and open-field test (OFT). The reactive oxygen species (ROS) generation was measured by DHE fluorescence staining or flow cytometry. Western blotting assay was used to detect the proteins of p-JNK, JNK, P53, PUMA, Bcl-2 and Bax in hippocampal tissue or HT22 cells treated with electrical stimulation. RESULTS: The serum MDA and 8-OHdG levels were increased (P < 0.001), while the activities of SOD and CAT were decreased (P < 0.001) significantly in patients with HVEB. Behavioral test results showed that high-voltage electric stimulation induced the PTSD-like symptoms and the ROS-JNK-P53 pathway was involved in the neuronal apoptosis in rats with PTSD induced by HVEB. In vitro experiments further confirmed the electrical stimulation induced neuronal apoptosis through ROS/JNK/P53 signaling pathway and the antioxidant NAC could rescued the ROS generation, activation of JNK/P53 proteins and improved the cell apoptosis rate in HT22 cells. Finally, the JNK inhibitor SP600125 could significantly inhibited the percentage of HT22 cell apoptosis induced by electrical stimulation (P < 0.001). CONCLUSIONS: These results indicated that oxidative stress mediates hippocampal neuronal apoptosis through ROS/JNK/P53 pathway in rats with PTSD triggered by HVEB.

12.
Res Involv Engagem ; 9(1): 82, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37697394

ABSTRACT

BACKGROUND: Approximately one in ten children globally live with kinship caregivers-relatives and family friends who step in to care for a child when parents are unable to do so. When families take on the role of informal kinship care-care of a child outside of the child welfare system-they often do so without financial assistance and advice in navigating the systems of support available to them. This is the unique role of kinship navigator programs in the U.S: to provide kinship caregivers a single point of entry for connecting to needed resources such as financial, health, housing, and legal assistance. METHODS: To the best of our knowledge, our team conducted one of the only participatory evaluations in which kinship caregivers were involved in all stages of evaluating a kinship navigator program-from designing the questions, to collecting and analyzing the data, to reporting the results. Black kinship caregivers took on decision-making power leading this formative evaluation of a kinship navigator program within one nonprofit organization in a Southeastern state. FINDINGS: In this paper we reflect on our process and offer lessons learned from engaging in participatory evaluation that may apply to the field of kinship care and across social service delivery more broadly. We focus on (1) ensuring the nonprofit's commitment to the study, (2) maintaining engagement through building relationships and facilitating a culture of learning within the study team, (3) sharing decision-making power so that people with lived experience have the authority and ownership to lead the evaluation, (4) developing team members' skills, confidence, and sense of belonging, and (5) increasing the likelihood the nonprofit will act on the study findings. CONCLUSION: Through this process, we learned that participatory evaluation is a feasible and useful approach both to understanding the experiences of kinship families and to improving the supports in their lives. We hope this paper will inspire others to draw on the strengths and capacity of people with lived experience to engage in participatory evaluation. Greater recognition of the value of this approach in social change and increased funding to carry out the process are both needed.


Involving people with lived experience in all stages of an evaluation can strengthen the credibility of the findings. This paper provides an example of this involvement. It focuses on a program designed to support kinship caregivers­those who step in to take care of a child when the parents are unable to do so. To the best of our knowledge, our team conducted one of the only participatory evaluations in which kinship caregivers were involved in all stages of evaluating a kinship navigator program in the U.S.­from designing the questions, to collecting and analyzing the data, to reporting the results. Through this process, we learned that participatory evaluation is a feasible and useful approach both to understanding the experiences of kinship families and to improving the supports in their lives. In this paper we share our collaborative journey through each stage of the evaluation, offering lessons learned about the process that may apply to the field of kinship care as well as to other areas of social service delivery.

13.
Funct Integr Genomics ; 23(3): 282, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37624450

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) might cause long-term burden of insomnia, while the common pathogenic mechanisms are not elucidated. The gene expression profiles of COVID-19 patients and healthy controls were retrieved from the GEO database, while gene set related with circadian rhythm was obtained from GeneCards database. Seventy-six shared genes were screened and mainly enriched in cell cycle, cell division, and cell proliferation, and 6 hub genes were found out including CCNA2, CCNB1, CDK1, CHEK1, MKI67, and TOP2A, with positive correlation to plasma cells. In the TF-gene regulatory network, NFYA, NFIC, MEF2A, and FOXC1 showed high connectivity with hub genes. This study identified six hub genes and might provide new insights into pathogenic mechanisms and novel clinical management strategies.


Subject(s)
COVID-19 , Humans , COVID-19/genetics , Cell Proliferation , Circadian Rhythm/genetics , Computational Biology
14.
Ecotoxicol Environ Saf ; 263: 115393, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37611479

ABSTRACT

Children are disproportionately represented among those who suffer asthma, which is a kind of chronic airway inflammation. Asthma symptoms might worsen when exposed to the air pollutant particulate matter 2.5 (PM2.5). However, it is becoming more prevalent among older adults, with more asthma-related deaths occurring in this pollution than in any other age group, and symptoms caused by asthma can reduce the quality of life of the elderly, whose asthma is underdiagnosed due to physiological factors. Therefore, in an effort to discover a therapy for older asthma during exposure to air pollution, we sought to ascertain the effects of pre-exposure (PA) and persistent exposure (PAP) to PM2.5 in aged asthma rats. In this study, we exposed aged rats to PM2.5 at different times (PA and PAP) and established an ovalbumin-mediated allergic asthma model. The basic process of elderly asthma caused by PM2.5 exposure was investigated by lung function detection, enzyme-linked immunosorbent assay (ELISA), histopathology, cytology, cytokine microarray, untargeted metabolomics, and gut microbiota analysis. Our findings demonstrated that in the PA and PAP groups, exposure to PM2.5 reduced lung function and exacerbated lung tissue damage, with varying degrees of effect on immunoglobulin levels, the findings of a cytological analysis, cytokines, and chemokines. The PA and PAP rats had higher amounts of polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, 2-methylNaphthalene, 1-methylNaphthalene and flourene. Moreover, exposure to PM2.5 at different times showed different effects on plasma metabolism and gut microbiota. Bioinformatics analysis showed a strong correlation between PAHs, cytokines, and gut microbiota, and PAHs may cause metabolic disorders through the gut microbiota. These findings point to a possible mechanism for the development of asthma in older people exposure to PM2.5 that may be related to past interactions between PAHs, cytokines, gut microbiota, and plasma metabolites.


Subject(s)
Asthma , Polycyclic Aromatic Hydrocarbons , Rats , Animals , Multiomics , Quality of Life , Asthma/chemically induced , Cytokines , Inflammation
15.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3671-3682, 2023 12.
Article in English | MEDLINE | ID: mdl-37294427

ABSTRACT

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with a high recurrence rate and heterogeneity. We aimed to examine the effect of corosolic acid (CRA) on HCC. We employed transcriptomics to validate the target molecules in CRA-treated HCC cells and conducted enrichment analyses that revealed their involvement in the regulation of endoplasmic reticulum (ER) stress and apoptosis. Our experimental data indicated that CRA markedly induced apoptosis in human HCC cell lines through the mitochondrial apoptosis pathway. We also revealed that the pro-apoptotic effects of CRA depended on ER stress, as pretreatment with selective ERS inhibitor salubrinal effectively reversed CRA-induced cell apoptosis. Furthermore, the knockdown of the unfolded protein response (UPR) protein CHOP remarkably abrogated CRA-induced expression of ER stress-associated proteins. Collectively, our results suggest that CRA triggers ER stress-mediated apoptosis in HCC cells via activation of the PERK-eIF2a-ATF4 pathway. Our findings provide novel insights into the potential therapeutic strategies for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Network Pharmacology , Endoplasmic Reticulum Stress , Apoptosis , Models, Theoretical , Transcription Factor CHOP/metabolism , Transcription Factor CHOP/pharmacology , Transcription Factor CHOP/therapeutic use , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/pharmacology
16.
BMC Complement Med Ther ; 23(1): 171, 2023 May 29.
Article in English | MEDLINE | ID: mdl-37248456

ABSTRACT

BACKGROUND: Corosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization. METHODS: Differentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting. RESULTS: A total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels. CONCLUSION: Our results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Triterpenes , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Cell Line , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Triterpenes/pharmacology , Network Pharmacology
17.
BMC Med Imaging ; 23(1): 53, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37041479

ABSTRACT

OBJECTIVE: This study aimed to explore the relationship between the ramus intermedius (RI) and atherosclerosis in the bifurcation of the left coronary artery (LCA). METHODS: Screening patients who underwent CCTA from January to September 2021, 100 patients with RI (RI group) and 100 patients without RI (no-RI group) were randomly enrolled, Evaluation of RI distribution characteristics and left main coronary artery(LM),Left anterior descending branch(LAD),left circumflex branch(LCX) proximal segment plaque distribution, measurement of LAD-LCX bifurcation angle(∠LAD-LCX),Comparison of the three distribution characteristics with the incidence of plaques in the left main trunk bifurcation area (LM, LAD, LCX) between groups and within the RI group. RESULTS: The difference in the incidence of plaques in the proximal LCX and the LM between the RI group and the no-RI group were not statistically significant (P > 0.05). The incidence of plaques in the proximal LAD in the RI group was significantly higher than that in the non-RI group (77% versus 53%, P < 0.05). However, there was no statistically significant difference between the two groups after PSM. A univariate logistic regression analysis revealed that an RI was a risk factor for plaque formation in the proximal LAD (P < 0.001), and a multivariate logistic regression analysis revealed that an RI was not an independent risk factor for plaque formation in the proximal LAD (P > 0.05). When compared within the RI group, the difference in the incidence of plaques in the proximal segment of LAD, the proximal segment of LCX, and the LM among the different distribution groups of RI was not statistically significant, respectively (P > 0.05). CONCLUSION: RI is not an independent risk factor for atherosclerosis in the left coronary artery bifurcation zone, but it may indirectly increase the risk of atherosclerosis in the proximal segment of the LAD.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Humans , Computed Tomography Angiography , Coronary Angiography/methods , Coronary Vessels , Tomography, X-Ray Computed
18.
J Acoust Soc Am ; 153(1): 348, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36732251

ABSTRACT

The main method to expand the operating bandwidth of the transducer is by exciting multi-order vibration modes, which develop from the earliest excitation of odd-order modes to the excitation of multi-order continuous modes. However, no detailed theoretical characterization of the excitation mechanism and electroacoustic properties of continuous-order modes has been given. In this paper, the excitation mechanism of continuous-order modes for one-dimensional thickness vibration is studied in detail. From the perspective of analytical characterization, the mathematical and physical conditions of mode excitation are analyzed and extended to continuous-order modes. Partial 1-3 piezocomposite consists of two parts; one part is complete lead zirconate-titanate and the other part is 1-3 composite, which is helpful for exciting continuous-order modes. Based on the excitation mechanism of continuous-order modes, a design method of broadband transducer used of partial 1-3 piezocomposite is proposed, and large bandwidth and good pulse response are obtained. The excitation mechanism of continuous-order modes proposed in this paper provides an idea for the theoretical analysis and design of multi-resonant broadband transducers.

19.
Ecotoxicol Environ Saf ; 252: 114580, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36706523

ABSTRACT

Silicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P<0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P<0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P<0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P<0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.


Subject(s)
Gastrointestinal Microbiome , Silicosis , Rats , Animals , Gastrointestinal Microbiome/genetics , Cytokines/metabolism , Rats, Wistar , Metabolome , Silicosis/metabolism , Silicon Dioxide/toxicity , RNA, Ribosomal, 16S/metabolism
20.
Ann Noninvasive Electrocardiol ; 28(1): e13027, 2023 01.
Article in English | MEDLINE | ID: mdl-36547015

ABSTRACT

OBJECTIVE: This study aims to explore the actual meaning of "false positive filling defect" in left atrial appendage (LAA) computed tomography (CT) in patients with atrial fibrillation (AF), with transesophageal echocardiography (TEE) as the gold standard. METHODS: Patients with AF undergoing cardiac CT angiography and TEE examinations for proposed radiofrequency catheter ablation between October 2020 and October 2021 were selected as the study subjects. Transesophageal echocardiography was taken as the "gold standard," and spontaneous echocardiographic contrast (SEC) and thrombus events were defined as positive events. The CT manifestations were classified into three groups (true positive, false positive, and true negative) to evaluate the differences in left atrium (LA) anterior-posterior diameter (LAAP), LA anterior wall thickness, and LAA orifice long diameter and short diameter, area, and depth between the three groups. RESULTS: (1) There was no statistical difference in LA anterior wall thickness between the three groups (p > .05); there was a statistical difference in LAAP (only) between the true-positive group and the true-negative group (p < .05). (2) There was a statistical difference in LAA orifice long diameter, short diameter, and area between the true-positive group and the true-negative group as well as between the false-positive group and the true-negative group (p < .05). (3) There was a statistical difference in LAA depth between the true-positive group and the false-positive group as well as between the true-positive group and the true-negative group (p < .05). (4) The area under the receiver operator characteristic curve (AUC) of LAA depth affecting the LAA thrombus and SEC was 0.863 (confidence interval = 0.718-1.000), the sensitivity was 77.8%, and the specificity was 90.6% for predicting the occurrence of LAA thrombus and SEC in patients with nonvalvular AF (NVAF) and an LAA depth of ≥50.84 mm. CONCLUSIONS: There was a difference in LAA diameter between the TEE-based CT false-positive group and the other groups. A "CT false positive" is an objectively existing state, and CT might be able to identify the LAA hemodynamic disorder earlier than TEE. Furthermore, a CT + TEE combined application could more accurately evaluate LAA hemodynamics in patients with AF.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Thrombosis , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Echocardiography, Transesophageal , Atrial Appendage/diagnostic imaging , Atrial Appendage/surgery , Electrocardiography , Heart Atria , Tomography, X-Ray Computed/methods , Contrast Media , Thrombosis/epidemiology
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