{"title":"Peptide pool instability of precancerous lesions in rats with chronic pancreatitis model and/or without type 1 diabetes mellitus.","authors":"Sergii Sukhodolia, Olesia Kalmukova, Natalia Raksha, Anatolyi Sukhodolia, Olena Kuryk, Olexiy Savchuk","doi":"10.17219/acem/193243","DOIUrl":"https://doi.org/10.17219/acem/193243","url":null,"abstract":"<p><strong>Background: </strong>The search for early and minimally invasive diagnostic approaches to pancreatic cancer (PC) remains an important issue. One of the most promising directions is to find a sensitive key in the metabolic changes during widespread causes of PC, i.e., chronic pancreatitis (CP) and diabetes mellitus (DM).</p><p><strong>Objectives: </strong>The main objective of this study was to analyze the peptide pools in the blood plasma and pancreas of rats with modeling of CP and/or without type 1 DM in association with pancreas histopathological grading features.</p><p><strong>Material and methods: </strong>The study was conducted on white non-linear male rats, divided into 3 groups: 1st group: control, 2nd group: rats with cerulein-stimulated CP, and 3rd group: rats with CP and streptozotocin-inducible type 1 DM. Total protein and peptide content were determined in the pancreas and blood plasma. The peptide pools were fractionated using size-exclusion chromatography.</p><p><strong>Results: </strong>Rats with CP showed a high degree of fibrosis in the pancreas and grade 1 ductal pancreatic intraepithelial neoplasia (PanIN), associated with decreased total peptides in the pancreas. In rats with CP and DM, 2nd and 3rd grade PanIN with pronounced acinar metaplasia was observed in association with decreasing total pancreatic protein and peptide pools. While there was a decrease in total protein and an increase in total peptide in blood serum, the changes were more pronounced in rats with CP and DM. A study revealed both qualitative and quantitative differences in the distribution of peptide pools in 2 groups with pathologies. Qualitatively, plasma samples from pathological groups exhibited an increased number of peaks. Quantitatively, there was a higher proportion of peptides with molecular weights exceeding 700 Da observed in both plasma and pancreas.</p><p><strong>Conclusions: </strong>The analysis of peptide pools obtained from plasma and PanIN development demonstrated that the peptide pool can serve as an early and complementary indicator of PC emergence.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of IGFBP3 and LGALS1 as potential secreted biomarkers for clear cell renal cell carcinoma based on bioinformatics analysis and machine learning.","authors":"Wunchana Seubwai, Sakkarn Sangkhamanon, Xuhong Zhang","doi":"10.17219/acem/194036","DOIUrl":"https://doi.org/10.17219/acem/194036","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Due to the lack of symptoms until advanced stages, early diagnosis of ccRCC is challenging. Therefore, the identification of novel secreted biomarkers for the early detection of ccRCC is urgently needed.</p><p><strong>Objectives: </strong>This study aimed to identify novel secreted biomarkers for diagnosing ccRCC using bioinformatics and machine learning techniques based on transcriptomics data.</p><p><strong>Material and methods: </strong>Differentially expressed genes (DEGs) in ccRCC compared to normal kidney tissues were identified using 3 transcriptomics datasets (GSE53757, GSE40435 and GSE11151) from the Gene Expression Omnibus (GEO). Potential secreted biomarkers were examined within these common DEGs using a list of human secretome proteins from The Human Protein Atlas. The recursive feature elimination (RFE) technique was used to determine the optimal number of features for building classification machine learning models. The expression levels and clinical associations of candidate biomarkers identified with RFE were validated using transcriptomics data from The Cancer Genome Atlas (TCGA). Classification models were then developed based on the expression levels of these candidate biomarkers. The performance of the models was evaluated based on accuracy, evaluation metrics, confusion matrices, and ROC-AUC (receiver operating characteristic-area under the ROC curve) curves.</p><p><strong>Results: </strong>We identified 44 DEGs that encode potential secreted proteins from 274 common DEGs found across all datasets. Among these, insulin-like growth factor binding protein 3 (IGFBP3) and lectin, galactoside-binding, soluble, 1 (LGALS1) were selected for further analysis using the RFE technique. Both IGFBP3 and LGALS1 showed significant upregulation in ccRCC tissues compared to normal tissues in the GEO and TCGA datasets. The results of the survival analysis indicated that patients with higher expression levels of these genes exhibited shorter overall and disease-free survival times (OS and DFS). Decision tree and random forest models based on IGFBP3 and LGALS1 levels achieved an accuracy of 98.04% and an AUC of 0.98.</p><p><strong>Conclusions: </strong>This study identified IGFBP3 and LGALS1 as promising novel secreted biomarkers for ccRCC diagnosis.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paweł Skorek, Magdalena M Frączek-Jucha, Agnieszka Sarnecka, Maciej Skubera, Natasza Libiszewska, Lidia Tomkiewicz-Pająk
{"title":"Experience with sodium glucose cotransporter-2 inhibitors in adult patients with Fontan circulation.","authors":"Paweł Skorek, Magdalena M Frączek-Jucha, Agnieszka Sarnecka, Maciej Skubera, Natasza Libiszewska, Lidia Tomkiewicz-Pająk","doi":"10.17219/acem/194617","DOIUrl":"https://doi.org/10.17219/acem/194617","url":null,"abstract":"<p><strong>Background: </strong>We still know little about the effective pharmacological treatment of heart failure (HF) associated with the Fontan circulation. One of the new options may be sodium glucose cotransporter-2 inhibitors (SGLT2i), which have been proven effective in classic forms of left ventricular HF.</p><p><strong>Objectives: </strong>To evaluate the effect and safety of SGLT2i inclusion in adults with Fontan circulation. To this end, we conducted observation and complex diagnostics of adult Fontan patients in whom we started treatment with flozins.</p><p><strong>Material and methods: </strong>The study population consisted of 17 adult Fontan patients with average age 30.5 (9.7) years, 59% in II New York Heart Association (NYHA) class, among whom 53% received dapagliflozin and rest empagliflozin.</p><p><strong>Results: </strong>The average observation time was 11.0 (3.7) months. None of the patients have reported side effects or complications related to treatment. We observed a significant increase (20.1 mL/kg/min vs 24.2 mL/kg/min, p = 0.008) in the median of maximum oxygen uptake (VO2 max) among participants (9) who completed at least 2 reliable cardiopulmonary exercise tests. We did not notice any significant differences in N-terminal prohormone of brain natriuretic peptide concentration (641.35 (923.7) vs 741.47 (1,139.02), p = 0.12) after the inclusion. Interestingly, we observed a significant increase in erythrocytes (+6%, p = 0.003), hemoglobin (+7%, p = 0.03) and hematocrit (+7%, p = 0.02).</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to demonstrate that the implementation of SGLT2i may have a positive effect on exercise capacity among adults with Fontan circulation. Our experience confirms the high safety of using these drugs in Fontan adults.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Umbelliferone inhibits proliferation and metastasis via modulating cadherin/β-catenin complex-aided cell-cell adhesion in glioblastoma cells.","authors":"Wei Ma, Hangyu Shi, Xinya Dong, Yongqiang Shi, Luyi Zhang, Bin Jiang","doi":"10.17219/acem/192547","DOIUrl":"https://doi.org/10.17219/acem/192547","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most aggressive brain tumor malignancy in adults, accounting for nearly 50% of all gliomas. Current medications for GBM frequently lead to drug resistance.</p><p><strong>Objectives: </strong>Umbelliferone (UMB) is found extensively in many plants and shows numerous pharmacological actions against inflammation, degenerative diseases and cancers. However, its anticancer effects on GBM cells have not yet been explored.</p><p><strong>Material and methods: </strong>This research intended to assess the antitumor efficacy of UMB and the molecular mechanism of cell-cell adhesion proteins in human U-87 GBM cells. The cytotoxicity assay, intracellular reactive oxygen species (ROS), cell adhesion proteins, and cell apoptosis actions of UMB were assessed using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT), dichlorodihydrofluorescein diacetate (DCFH-DA), 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and western blot.</p><p><strong>Results: </strong>The findings revealed that UMB reduced the proliferation of GBM cells and cell adhesion proteins, while augmenting apoptosis through the elevation of cellular ROS. Bcl-2 family protein levels of Bcl-2 and Bcl-XL were mitigated; conversely, the pro-apoptotic proteins Bad and Bim were elevated upon treatment with UMB in a quantity-dependent way. Furthermore, UMB-treated GBM cells suppressed N-cadherin, β-catenin, Slug, and matrix metalloproteinase 2 (MMP-2) expression, whereas they showed enhanced TIMP protein and E-cadherin levels.</p><p><strong>Conclusions: </strong>Our findings suggest that UMB can prevent proliferation and metastasis and stimulate apoptosis in GBM cells.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanjun Xu, Jing Yang, Zexing Jiang, Peng Liu, Xudong Wang
{"title":"Association between stress-induced hyperglycemia ratio and sepsis risk in patients admitted to ICU.","authors":"Yanjun Xu, Jing Yang, Zexing Jiang, Peng Liu, Xudong Wang","doi":"10.17219/acem/194503","DOIUrl":"https://doi.org/10.17219/acem/194503","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening condition characterized by a dysregulated host immune response to infection. Currently, stress hyperglycemia is frequently associated with an unfavorable prognosis in cardiovascular and cerebrovascular disease. During sepsis, the progression of the immune response and inflammation often leads to aberrant metabolic indicators. However, the association between the stress-induced hyperglycemia ratio (SHR) and sepsis in patients admitted to the intensive care unit (ICU) remains uncertain.</p><p><strong>Objectives: </strong>This study aimed to explore the potential correlation between SHR and sepsis.</p><p><strong>Material and methods: </strong>In this retrospective cohort study, data were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Patients with recorded glucose and glycosylated HbA1c levels within 24-h ICU admission were identified. The endpoints of the follow-up period were the occurrence of sepsis during ICU stay or ICU discharge. After adjustment for factors including demographics, vital signs and biochemical indicators, the univariate and multivariate logistic regression model was employed to examine the relationship between SHR, baseline blood glucose levels and the risk of sepsis. The associations were further explored in subgroups based on age, gender and presence/absence of type 2 diabetes.</p><p><strong>Results: </strong>Of the total 2,161 patients, with the average age of 64.96 ±16.84 years, 205 (9.49%) had sepsis. After adjustment or confounders, high SHR levels were associated with the risk of sepsis odds ratio (OR) = 1.53, 95% confidence interval (95% CI): 1.07-2.17). Similar results were found in patients aged ≥65 years (OR = 1.91, 95% CI: 1.16-3.17), in men (OR = 1.64, 95% CI: 1.02-2.63) and patients without type 2 diabetes history (OR = 1.58, 95% CI: 1.01-2.48). The baseline blood glucose level did not exhibit a significant association with the risk of sepsis.</p><p><strong>Conclusions: </strong>Elevated SHR levels were correlated with sepsis. Bedside monitoring of SHR may be a valuable tool for clinicians to identify patients at high risk of sepsis, and be beneficial to promptly implement clinical interventions.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ponnusamy Subramaniam, Preyaangka Thillainathan, Anthony Angwin, Shobha Sharma
{"title":"Unfolding memories: Crafting digital life storybooks for dementia care via telehealth.","authors":"Ponnusamy Subramaniam, Preyaangka Thillainathan, Anthony Angwin, Shobha Sharma","doi":"10.17219/acem/194410","DOIUrl":"https://doi.org/10.17219/acem/194410","url":null,"abstract":"<p><strong>Background: </strong>Dementia, a rapidly growing cognitive disorder, has a profound impact on the lives of individuals and their caregivers across the globe. Digital life storybooks have emerged as a promising non-pharmacological intervention to improve the wellbeing of people living with dementia (PLWD).</p><p><strong>Objectives: </strong>This study aims to investigate the feasibility of developing and applying a digital life storybook for PLWD using telehealth, while evaluating its impact on communication skills, quality of life (QoL) and satisfaction levels.</p><p><strong>Material and methods: </strong>A mixed-method study design will be employed, involving pairs of PLWD and their primary caregivers (dyads) recruited from a teaching hospital and a non-profit organization in Malaysia. The intervention involves the creation and use of a digital life storybook facilitated remotely via telehealth channels. Data will be collected at 6 points in time: prior to the commencement of development, prior to the submission of an application, on a biweekly basis, and at the conclusion of the assessment period. Quantitative measures will include the Holden Communication Scale, Quality of Life-Alzheimer's Disease Scale (QoL-AD) and Quality of the Caregiving Relationship (QCPR) questionnaire. Qualitative data will be gathered through validated open-ended questions.</p><p><strong>Results: </strong>Implications of the study include facilitating future research, contributing to person-centered care practices, and providing caregivers with tools to better understand and connect with PLWD. The findings will contribute to the understanding of the mechanisms through which digital life storybooks can benefit PLWD and their caregivers.</p><p><strong>Conclusion: </strong>The successful implementation of this protocol could have significant implications for dementia care in both formal and informal settings, and could ultimately improve the lives of those affected by dementia.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human umbilical cord mesenchymal stem cell-derived exosomes combined with mouse nerve growth factor can more effectively ameliorate the motor disorder and brain pathological injury in mice with cerebral palsy.","authors":"Xingxing Chen, Yipa Sai, Weijing Cui, Xiaoxia Hu, Jing Liu, Xiaofeng Cao, Shili Wu","doi":"10.17219/acem/192773","DOIUrl":"https://doi.org/10.17219/acem/192773","url":null,"abstract":"<p><strong>Background: </strong>Cerebral palsy (CP) is a neurodevelopmental disorder and motor disorder syndrome. It has been confirmed that mesenchymal stem cells (MSCs) and mouse nerve growth factor (mNGF) can repair brain tissue damage and nerve injury; however, exosomes derived from healthy cells may have a comparable therapeutic potential as the cells themselves.</p><p><strong>Objectives: </strong>The purpose of this study was to explore the improvement effect of human umbilical cord mesenchymal stem cell (hUC-MSCs)-derived exosomes on a CP model and determine whether there is a synergistic effect when combined with mNGF.</p><p><strong>Material and methods: </strong>Exosomes were isolated from hUC-MSCs and examined using transmission electron microscopy (TEM), particle size and western blot (WB). A total of 38 BALB/c mice (male, postnatal day 6 (PND6)) were randomly divided into 5 groups: sham group, CP group, CP-exo group, CP-mNGF group, and CP-exo-mNGF group. Hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide (LPS) infection was used to construct the CP model. Pathological damage to neuron tissue and synaptic structures in the hippocampus was confirmed using light microscopy after hematoxylin-eosin (H&E) staining and TEM, respectively. Survival of neurons was evaluated using Nissl staining. Western blot was applied to monitor PSD-95 and synaptophysin (SYN) protein levels.</p><p><strong>Results: </strong>This study indicated that exosomes released by hUC-MSCs ameliorated brain damage and synaptic structure destruction in CP mice induced by hypoxic ischemia and LPS infection. When combined with mNGF, there was more effective improvement. In the CP group, neuronal function was severely impaired; however, hUC-MSCs-derived exosomes and mNGF improved it. PSD-95 and SYN proteins were presynaptic and postsynaptic proteins, respectively. Interestingly, the PSD-95 and SYN protein levels were significantly lower in the CP mice, but with the addition of hUC-MSCs-exosomes or mNGF, they increased significantly, especially in the CP-exo-mNGF group.</p><p><strong>Conclusions: </strong>The nerve function injury in CP can be improved the most when hUC-MSCs-derived exosomes are combined with mNGF through intraperitoneal (ip.) administration.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Se-Kwon Kim, Venkatesan Jayachandran, Thanh Sang Vo, Isuru Wijesekara
{"title":"Safety assessment of turmeric-boswellia-sesame formulation in healthy adult volunteers: An open-label prospective study.","authors":"Se-Kwon Kim, Venkatesan Jayachandran, Thanh Sang Vo, Isuru Wijesekara","doi":"10.17219/acem/193023","DOIUrl":"https://doi.org/10.17219/acem/193023","url":null,"abstract":"<p><strong>Background: </strong>Turmeric and boswellia supplements have gained popularity for their anti-inflammatory and antioxidant properties. It is important to critically assess the safety of such supplements for prolonged use.</p><p><strong>Objectives: </strong>To assess the safety and tolerability of turmeric-boswellia-sesame oil formulation (TBSF) in healthy human volunteers.</p><p><strong>Material and methods: </strong>Forty participants were supplemented with TBSF at a dose of 2,000 mg daily for 90 days. Safety assessments were performed at baseline, as well as on day 30, 60 and 90. Adverse events were monitored throughout the study period. Any evidence of hepatotoxicity injury or drug induced liver injury (DILI) was assessed using R value (R ratio/R factor), which is a relative pattern of liver enzymes. Additionally, Hy's law criteria, based on liver enzymes and bilirubin levels, were employed, along with an evaluation of drug-induced serious hepatotoxicity (eDISH) plot. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated, as these values are relevant to the safety of the intervention.</p><p><strong>Results: </strong>The study found that TBSF supplementation did not cause any adverse effects or clinically significant variations in vital signs, hematological parameters, lipid profile, liver function enzymes, and renal function markers, and all were within the normal range after 90 days of TBSF supplementation. Platelet-to-lymphocyte ratio and NLR did not change significantly and were within the normal range. All the participants when plotted were in the normal range quadrant of the eDISH plot throughout the study period. No abnormal findings were observed in R value and Hy's law criteria, indicating that TBSF does not induce any hepatotoxicity. The present study showed a normal estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine (Cr), Cr clearance, and BUN/Cr ratio throughout the study period. There was no significant change between these values at 4 abovementioned time points.</p><p><strong>Conclusions: </strong>The study findings suggest that TBSF is a safe supplement for regular and long-term consumption.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of downregulation of ARL9 expression on the proliferation, metastasis and biological behavior of AGS gastric cancer cell lines.","authors":"Caihua Sun, Hongliang Yao, Jipan Liu, Shuai Wang","doi":"10.17219/acem/193399","DOIUrl":"https://doi.org/10.17219/acem/193399","url":null,"abstract":"<p><strong>Background: </strong>Some ADP ribosylation factors (ARF) and ADP ribosylation factor-like (ARL) family are involved in the regulation of certain cancers, but the role of ADP ribosylation factor-like 9 (ARL9) in gastric tumorigenesis remains elusive.</p><p><strong>Objectives: </strong>The main aim of this study was to evaluate the ARL9 expression within stomach cancer cells and elucidate its influence on the modulation of cancer cell behavior.</p><p><strong>Material and methods: </strong>Differential ARL9 protein expression in normal stomach and stomach cancer tissue was ascertained through data sourced from the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). Quantitative analysis of ARL9 expression in gastric cancer tissue and its association with clinicopathological features was performed using quantitative polymerase chain reaction (qPCR) and western blot analysis (WB). Small interfering RNA (siRNA) was employed to suppress ARL9 protein expression in the human stomach gastric adenocarcinoma human gastric adenocarcinoma cells (AGS) cell line. Assessment of AGS gastric cancer (GC) cell proliferation, invasion and migration was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell techniques.</p><p><strong>Results: </strong>The expression of ARL9 protein exhibited a significant upregulation in GC tissue, and showed a close association between tumor dimensions (p < 0.05) and the presence of distant metastases (p < 0.05) among individuals diagnosed with GC. However, no significant link was observed with sex, age and tumor-node-metastasis (TNM) staging in gastric malignancy patients. After the introduction of si-ARL9 in the experimental set, there was a noteworthy decrease in ARL9 protein levels in AGS cells (p < 0.01). In contrast to the control cohort, the restraint of ARL9 expression significantly hampered the growth, mobility and infiltration abilities of the AGS GC cell line (p < 0.01).</p><p><strong>Conclusions: </strong>The significant correlation of ARL9 with the biological behavior of GC indicates its potentially pivotal role in the pathophysiology of the malignancy.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Renal protection by acacetin in streptozotocin-induced diabetic nephropathy via TLR4/NF-κB pathway modulation in rats.","authors":"Hangying Yu, Min Guo","doi":"10.17219/acem/192225","DOIUrl":"https://doi.org/10.17219/acem/192225","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN), the most severe microvascular consequence of diabetes mellitus (DM), is the precursor to end-stage renal disease (ESRD). The development of problems linked to DN involves both oxidative damage and inflammation. Natural flavone acacetin (AC) has anti-inflammatory, antioxidant and anti-cancer properties. However, the effect of AC on DN is not clear.</p><p><strong>Objectives: </strong>To investigate potential nephroprotective effects of AC caused by reducing inflammation and oxidative stress via the TLR4/NF-κB pathway in rats with streptozotocin (STZ)-induced DN.</p><p><strong>Material and methods: </strong>In this study, we investigated the nephroprotective effect of AC compared to that of a positive control therapy of irbesartan (IRB) in DN induced with STZ. In this model, rats were given an intraperitoneal injection of STZ (180 mg/kg body weight (BW)), along with daily doses of AC (10 mg/kg BW) or IRB (180 mg/kg BW) to induce DN. Histopathology, albumin, blood glucose (Bg), BW, oxidative stress indicators, and western blot of inflammatory signaling pathways in the kidney were examined.</p><p><strong>Results: </strong>Reduction of blood glucose, proteinuria, serum malondialdehyde (MDA), serum creatinine, and blood urea nitrogen (BUN), as well as the inhibition of toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1) and nuclear factor kappa B (NF-κB) protein expression were observed. These data demonstrated that AC could improve BW, antioxidant enzyme and renal histopathology in rats with STZ-induced DN.</p><p><strong>Conclusions: </strong>Results from the rat model highlight how AC-suppressed inflammation and oxidative stress can attenuate STZ-induced DN by downregulating the TLR4/NF-κB pathway in rats.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}