|
|
- Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of
Nonalcoholic Fatty Liver Disease in Childhood Obesity-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity. Methods Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD. Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44–0.67) versus 0.44 (0.34–0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015–1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059–1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008–1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045–1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors. Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity. PubDate: 2024-08-03
- Development and Validation of a Carbohydrate Metabolism-Related Model for
Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. Methods The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. Results A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. Conclusion Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients. PubDate: 2024-08-03
- Synergistic Effects of Glutamine Deprivation and Metformin in Acute
Myeloid Leukemia-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective The metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells. Methods SKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown. Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells. Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML. PubDate: 2024-08-03
- Soluble ST2: A Novel Biomarker for Diagnosis and Prognosis of
Cardiovascular Disease-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract The increasing incidence of cardiovascular disease (CVD) is a significant global health concern, affecting millions of individuals each year. Accurate diagnosis of acute CVD poses a formidable challenge, as misdiagnosis can significantly decrease patient survival rates. Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs, but they can be influenced by various factors, such as age, sex, and renal function. Soluble ST2 (sST2) is a novel biomarker that is closely associated with different CVDs. Its low reference change value makes it suitable for continuous measurement, unaffected by age, kidney function, and other confounding factors, facilitating risk stratification of CVDs. Furthermore, the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value. This review aims to provide a comprehensive overview of sST2, focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2. PubDate: 2024-08-03
- A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on
Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. Methods This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. Results In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON. PubDate: 2024-08-03
- Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via
Mitophagy-induced Apoptosis-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. Methods Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. Results MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. Conclusion Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer. PubDate: 2024-08-03
- Research Progress on the Pathogenesis and Treatment of Neoatherosclerosis
-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Abstract Neoatherosclerosis (NA) within stents has become an important clinical problem after coronary artery stent implantation. In-stent restenosis and in-stent thrombosis are the two major complications following coronary stent placement and seriously affect patient prognosis. As the common pathological basis of these two complications, NA plaques, unlike native atherosclerotic plaques, often grow around residual oxidized lipids and stent struts. The main components are foam cells formed by vascular smooth muscle cells (VSMCs) engulfing oxidized lipids at lipid residue sites. Current research mainly focuses on optical coherence tomography (OCT) and intravascular ultrasound (IVUS), but the specific pathogenesis of NA is still unclear. A thorough understanding of the pathogenesis and pathological features of NA provides a theoretical basis for clinical treatment. This article reviews the previous research of our research group and the current situation of domestic and foreign research. PubDate: 2024-08-03
- Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes
Mellitus in China-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population. Methods Clinical data of 30 693 inpatients who were diagnosed with type 2 diabetes mellitus (T2DM) and admitted between 2013 and 2018 were retrospectively analyzed. The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data, and risk factors were analyzed by multiple imputation and regression. Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4% and 21.5%, respectively, and 85.2% of the stroke patients had ischemic stroke. Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors. Compared with no-risk-factor clustering, the risk of stroke significantly increased 3–4 times in the presence of more than 4 risk-factor clusters (P<0.001). Hypertension was the most common major risk factor for ischemic stroke [odds ratio (OR), 2.34; 95% confidence interval (CI), 2.18–2.50] and hemorrhagic stroke (OR, 3.68; 95% CI 2.95–4.59; P<0.001). Moreover, a 1-standard-deviation increase in fasting blood glucose (FBG) was significantly negatively correlated with ischemic stroke risk, and the same change in FBG was significantly associated with an 8% increased risk of hemorrhagic stroke. Conclusion The prevalence of stroke in patients with T2DM is rather high, and the clustering of risk factors is associated with the development of stroke in T2DM patients. Risk factors differ in different stroke subtypes. Identifying risk factors for a specific high-risk group is necessary. PubDate: 2024-07-23
- Protective Effects of Berberine on Nonalcoholic Fatty Liver Disease in
db/db Mice via AMPK/SIRT1 Pathway Activation-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Berberine (BBR) has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease (NAFLD). This study aims to elucidate the underlying molecular mechanisms. Methods In this study, db/db mice were chosen as an animal model for NAFLD. A total of 10 healthy C57BL/6J mice and 30 db/db mice were randomly allocated to one of 4 groups: the normal control (NC) group, the diabetic control (DC) group, the Metformin (MET) therapy group, and the BBR therapy group. The total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were measured. The glutathione peroxidase (GSH-Px), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein 1 (MCP-1) levels in liver tissue were measured. Hematoxylin and eosin (H&E), acid-Schiff (PAS) and TUNEL stanning was performed for histopathological analysis. Western blotting and immunohistochemistry were conducted to detect the expression levels of key proteins in the AMPK/SIRT1 pathway. Results BBR could improve lipid metabolism, attenuate hepatic steatosis and alleviate liver injury significantly. The excessive oxidative stress, high levels of inflammation and abnormal apoptosis in db/db mice were reversed after BBR intervention. BBR clearly changed the expression of AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1), and their downstream proteins. Conclusion BBR could reverse NAFLD-related liver injury, likely by activating the AMPK/SIRT1 signaling pathway to inhibit oxidative stress, inflammation and apoptosis in hepatic tissue. PubDate: 2024-07-23
- Traditional Chinese Medicine Erhuang Suppository for Treatment of
Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. Methods In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. Results After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. Conclusion This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases. PubDate: 2024-07-23
- Role of Vickers Ligament in the Pathogenesis of Madelung Deformity
-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius, leading to Madelung deformity. The purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers ligament. Methods All 22 patients (33 wrists) with Madelung deformities treated surgically between 2018 and 2022 were included. The diagnosis was confirmed radiographically in all patients. The three-dimensional computed tomography (3D-CT) data of 16 patients (19 wrists) were available. Magnetic resonance imaging (MRI) data were available for 9 patients (14 wrists). Wrist arthroscopy was used in 4 patients. The Vickers ligament was resected and submitted for histopathological examination in 8 patients. Radiographic outcomes, 3D-CT, MRI, arthroscopy, surgical findings, and histopathology of the Vickers ligament were evaluated. Results The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar radius. In the sequential MR coronal images, the Vickers ligament could be divided into 3 branches, extending to the lunate, triquetrum and ulnar styloid. Arthroscopy and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the wrist. The histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex (TFCC). Conclusions The Vickers ligament is not a separate aberrant ligament. The nature of the Vickers ligament is a combination of the stretched TFCC ligament (palmar radioulnar ligament, ulnotriquetral ligament and ulnolunate ligament) and radiolunate ligament. The possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch, which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to form the Vickers ligament. PubDate: 2024-07-19
- Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting
Serotonergic Neurons in Dorsal Raphe Nucleus-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Alzheimer’s disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. Results EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD. PubDate: 2024-07-11
- Risk Factors and Predictive Nomogram for Survival in Elderly Patients with
Brain Glioma-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram. Methods Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA). Results A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance. Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making. PubDate: 2024-07-11
- LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder
Cancer Cells through the Snail/E-cadherin Axis-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective This study aimed to investigate the role of the long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in the epithelial-mesenchymal transition (EMT) of bladder cancer cells and the potential mechanisms. Methods Cell invasion, migration, and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells. The expression levels of E-cadherin were measured using Western blotting, RT-qPCR, and dual luciferase reporter assays. RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets. Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin. The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin. Additionally, MEG3 suppressed the phosphorylation of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, thereby decreasing the expression of Snail and stimulating the expression of E-cadherin. Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells, indicating its potential as a promising therapeutic target for the treatment of bladder cancer. PubDate: 2024-07-11
- Psychological Status and Warfarin Therapy in Patients after Valve
Replacement during the COVID-19 Pandemic: A Cross-sectional Study-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. Methods Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. Results A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. Conclusion During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement. PubDate: 2024-07-06
- USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced
Dysfunction in HK-2 Cells-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy (DN). Here, we identified the functions of ubiquitin-specific peptidase 19 (USP19) in HK-2 cells exposed to a combination of high glucose (HG) and free fatty acid (FFA) and determined its association with TGF-beta-activated kinase 1 (TAK1). Methods HK-2 cells were exposed to a combination of HG and FFA. USP19 mRNA expression was detected by quantitative RT-PCR (qRT-PCR), and protein analysis was performed by immunoblotting (IB). Cell growth was assessed by Cell Counting Kit-8 (CCK-8) viability and 5-ethynyl-2′-deoxyuridine (EdU) proliferation assays. Cell cycle distribution and apoptosis were detected by flow cytometry. The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation (Co-IP) assays and IB. Results In HG+FFA-challenged HK-2 cells, USP19 was highly expressed. USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells. Moreover, USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1 (PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species (ROS) generation in HK-2 cells. Mechanistically, USP19 stabilized the TAK1 protein through deubiquitination. Importantly, increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells. Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1, providing a potential therapeutic strategy for combating DN. PubDate: 2024-07-05
- Notopterygium Incisum Extract Promotes Apoptosis by Preventing the
Degradation of BIM in Colorectal Cancer-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. Methods The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. Results QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. Conclusion QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM. PubDate: 2024-07-05
- Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in
Chinese Aniridia Families-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. Results A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. Conclusion In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families. PubDate: 2024-07-05
- Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib
Sensitivity in Hepatocellular Carcinoma Cells-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Mitofusin-2 (MFN2) is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism. To further elucidate the impact of MFN2, this study aimed to investigate its significance on hepatocellular carcinoma (HCC) cell function and its potential role in mediating chemosensitivity. Methods This study investigated the effects of silencing and overexpressing MFN2 on the survival, proliferation, invasion and migration abilities, and sorafenib resistance of MHCC97-L HCC cells. Additional experiments were conducted using XAV939 (a β-catenin inhibitor) and HLY78 (a β-catenin activator) to further validate these findings. Results Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells, enhanced their invasion and migration capacities, increased the IC50 of sorafenib, reduced the percentage of TUNEL-positive cells, and decreased the expression of proapoptotic proteins. Additionally, silencing MFN2 markedly induced the nuclear translocation of β-catenin, increased β-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression. Conversely, overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above. The results confirmed that silencing MFN2 activated the β-catenin/epithelial-mesenchymal transition (EMT) pathway and reduced the sensitivity of cells to sorafenib, which could be reversed by XAV939 treatment. Conversely, overexpression of MFN2 inhibited the β-catenin/EMT pathway and increased the sensitivity of cells to sorafenib, which could be altered by HLY78. Conclusion Low expression of MFN2 in HCC cells promotes the nuclear translocation of β-catenin, thereby activating the EMT pathway and mediating resistance to sorafenib. PubDate: 2024-06-27
- High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating
Piezo1-
Free pre-print version: Loading...
Rate this result:
What is this?
Please help us test our new pre-print finding feature by giving the pre-print link a rating. A 5 star rating indicates the linked pre-print has the exact same content as the published article.
Abstract: Objective Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis. Methods Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH2O) or exposed to HHP (50 cmH2O or 100 cmH2O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism. Results The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors. Conclusion The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1. PubDate: 2024-06-27
|