Archives of Medical Research最新文献

{"title":"GEMIN4 Variants: Risk Profiling, Bioinformatics, and Dynamic Simulations Uncover Susceptibility to Bladder Carcinoma","authors":"Abdallah S. Mohamed ,&nbsp;Afrah F. Salama ,&nbsp;Magdy A. Sabaa ,&nbsp;Eman Toraih ,&nbsp;Rami M. Elshazli","doi":"10.1016/j.arcmed.2024.102970","DOIUrl":"https://doi.org/10.1016/j.arcmed.2024.102970","url":null,"abstract":"<div><h3>Background</h3><p>The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations.</p></div><div><h3>Methods</h3><p>A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares.</p></div><div><h3>Results</h3><p>The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, <em>p</em> = 0.002) and recessive (OR = 0.54, <em>p</em> = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, <em>p</em> = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, <em>p</em> = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations.</p></div><div><h3>Conclusions</h3><p>The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0188440924000237/pdfft?md5=eceb7a893ea57109bcba414cf6da3e02&pid=1-s2.0-S0188440924000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139942481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of Vitamin D Status in Healthy Young Adults from Mexico City","authors":"Alva Belen Morales-Villar ,&nbsp;Jorge Maldonado-Hernández ,&nbsp;Nelson Eduardo Álvarez-Licona ,&nbsp;Mónica Ivette Piña-Aguero ,&nbsp;Salvador Villalpando-Hernández ,&nbsp;Ricardo Martín Robledo-Pérez ,&nbsp;Ismael Díaz-Rangel ,&nbsp;María de Lourdes Barbosa-Cortés ,&nbsp;Benjamín-Armando Núñez-García","doi":"10.1016/j.arcmed.2024.102968","DOIUrl":"https://doi.org/10.1016/j.arcmed.2024.102968","url":null,"abstract":"<div><h3>Background and Aims</h3><p>Vitamin D deficiency is a global health problem. The determinants of this deficiency have not been evaluated in developing countries such as Mexico. Thus, this study aimed to determine vitamin D intake and sun exposure and its relationship with plasma concentrations of 25-hydroxyvitamin D -25(OH)D- in young adults from Mexico City.</p></div><div><h3>Methods</h3><p>One hundred fifty five urban adult subjects were enrolled during 2017 and 2018. Sociodemographic, anthropometric, and clinical data, vitamin D intake, and sun exposure habits were collected. Plasma concentrations of 25(OH)D were also determined.</p></div><div><h3>Results</h3><p>The proportion of vitamin D deficiency was significantly higher in women than in men (65.7 vs. 43.4%, <em>p</em> = 0.012). The overall median dietary vitamin D intake was 112 IU/d (less than 20% of the recommended daily intake; RDI). 25-hydroxyvitamin D correlated directly with vitamin D intake, sun exposure score, waist-to-hip ratio, and age; an inverse significant association was found with body fat percentage. A multiple regression analysis was performed; simultaneous and significant (<em>p</em> &lt;0.01) effects of sun exposure score, dietary vitamin D, the season of the year (spring-summer vs. fall-winter), and age were observed on 25(OH)D levels.</p></div><div><h3>Conclusion</h3><p>High rates of vitamin D deficiency and insufficiency were observed in young adults from Mexico City. According to the RDI of this vitamin, its consumption, assessed by a 24 h multi-step nutritional questionnaire, was significantly low. A linear multiple regression model identified several predictors of plasma 25(OH)D concentrations. This multiple regression model was statistically validated.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repositioning FDA-Approved Drug Against Chagas Disease and Cutaneous Leishmaniosis by Structure-Based Virtual Screening","authors":"Alfredo Juarez-Saldivar ,&nbsp;Rogelio Gómez-Escobedo ,&nbsp;Gerardo Corral-Ruiz ,&nbsp;Karla Fabiola Chacón-Vargas ,&nbsp;Vanessa Horta-Montaño ,&nbsp;Luvia Sanchez-Torres ,&nbsp;Lenci k. Vazquez-Jimenez ,&nbsp;Benjamín Nogueda-Torres ,&nbsp;Gildardo Rivera","doi":"10.1016/j.arcmed.2024.102958","DOIUrl":"10.1016/j.arcmed.2024.102958","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Chagas disease and </span>cutaneous leishmaniasis, two parasitic diseases caused by </span><span><em>Trypanosoma cruzi</em></span> (<em>T. cruzi</em>) and <span><em>Leishmania mexicana</em></span> (<em>L. mexicana</em><span>), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs.</span></p></div><div><h3>Methods</h3><p><span><span>Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved </span>drug library against </span><em>Trypanosoma cruzi</em> and <em>Leishmania mexicana</em><span><span> glycolytic enzyme </span>triosephosphate isomerase<span> (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested </span></span><em>in vitro</em> to confirm their biological activity.</p></div><div><h3>Results</h3><p><span>The study showed that five compounds: nilotinib<span><span>, chlorhexidine, </span>protriptyline<span>, cyproheptadine, and montelukast, were more active against </span></span></span><em>T. cruzi</em><span><span>, than the reference drugs, nifurtimox and </span>benznidazole while chlorhexidine and protriptyline were the most active against </span><em>L. mexicana</em>.</p></div><div><h3>Conclusions</h3><p>The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De Novo Vitiligo Following Covid-19 Infection and Vaccination: A Door Open to Future Events?","authors":"RAFFAELLA MORMILE","doi":"10.1016/j.arcmed.2024.102961","DOIUrl":"10.1016/j.arcmed.2024.102961","url":null,"abstract":"","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139645641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Prevalence and Severity of Retinopathy of Prematurity over the Last Four Decades (1985–2021): A Systematic Review and Meta-Analysis","authors":"Heladia García ,&nbsp;Miguel Angel Villasis-Keever ,&nbsp;Georgina Zavala-Vargas ,&nbsp;Juan Carlos Bravo-Ortiz ,&nbsp;Ayari Pérez-Méndez ,&nbsp;Alberto Escamilla-Núñez","doi":"10.1016/j.arcmed.2024.102967","DOIUrl":"10.1016/j.arcmed.2024.102967","url":null,"abstract":"<div><h3>Background</h3><p>Retinopathy of prematurity (ROP) is a vasoproliferative disease of the retina that occurs in premature infants. The prevalence of ROP reported so far is inconsistent.</p></div><div><h3>Aim</h3><p>To conduct a systematic review to describe the trend of ROP prevalence between 1985 and 2021, and to determine the influence of countries’ economic conditions on ROP prevalence.</p></div><div><h3>Methods</h3><p>We searched PubMed, Embase, and Google Scholar for studies published between January 1985 and December 2021 using the following MeSH terms: “retinopathy of prematurity”, “ROP”, “incidence”, and “prevalence”. Two independent reviewers examined the articles to select studies that met the selection criteria and performed data extraction and study quality assessment. For the meta-analysis, the pooled prevalence was calculated using a random-effects model and R software.</p></div><div><h3>Results</h3><p>Of 5,250 titles and abstracts, 139 original studies met the inclusion criteria; a total of 121,618 premature infants were included in these studies. The pooled prevalence of ROP was 31.9% (95% confidence interval [CI] 29.0–34.8) and that of severe ROP was 7.5% (6.5–8.7). In general, no significant differences in prevalence were found over the four decades; however, we found a higher prevalence in premature infants ≤28 weeks of gestational age. In addition, the highest ROP prevalence was found in lower-middle-income countries with high mortality rates. In contrast, the highest severe ROP prevalence was found in high-income countries.</p></div><div><h3>Conclusion</h3><p>ROP remains a common cause of morbidity in premature infants worldwide. Therefore, it seems necessary to maintain early identification strategies for patients at higher risk, particularly in low- and middle-income countries.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial","authors":"Graciela Cárdenas ,&nbsp;María Chávez-Canales ,&nbsp;Ana María Espinosa ,&nbsp;Antonio Jordán-Ríos ,&nbsp;Daniel Anica Malagon ,&nbsp;Manlio Fabio Márquez Murillo ,&nbsp;Laura Victoria Torres Araujo ,&nbsp;Ricardo Leopoldo Barajas Campos ,&nbsp;Rosa María Wong-Chew ,&nbsp;Luis Esteban Ramirez González ,&nbsp;Karent Ibet Cresencio ,&nbsp;Enrique García Velázquez ,&nbsp;Mariana Rodriguez de la Cerda ,&nbsp;Yoana Leyva ,&nbsp;Joselin Hernández-Ruiz ,&nbsp;María Luisa Hernández-Medel ,&nbsp;Mireya León-Hernández ,&nbsp;Karen Medina Quero ,&nbsp;Anahí Sánchez Monciváis ,&nbsp;Eduardo Beltrán Sarmiento ,&nbsp;Edda Sciutto","doi":"10.1016/j.arcmed.2024.102960","DOIUrl":"10.1016/j.arcmed.2024.102960","url":null,"abstract":"<div><h3>Background</h3><p><span><span><span>SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury<span> and even death. The virus<span> also invades the central nervous system (CNS), causing </span></span></span>neuroinflammation and death from central failure. Intravenous (IV) or oral </span>dexamethasone (DXM) reduced 28 d mortality </span>in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability.</p></div><div><h3>Aims</h3><p>To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19.</p></div><div><h3>Methods</h3><p>A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded.</p></div><div><h3>Results</h3><p>Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died.</p></div><div><h3>Conclusions</h3><p>IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating a Novel Newborn Screening Methodology: Combined Genetic and Biochemical Screenings","authors":"Bin Yu ,&nbsp;Yuqi Yang ,&nbsp;Lingna Zhou ,&nbsp;Qiuwei Wang","doi":"10.1016/j.arcmed.2024.102959","DOIUrl":"10.1016/j.arcmed.2024.102959","url":null,"abstract":"<div><h3>Purpose</h3><p>Analysis of four newborn screening<span><span> modes using newborn </span>genomic sequencing (nGS) and traditional biochemical screening (TBS).</span></p></div><div><h3>Methods</h3><p>Prospective clinical study with a total of 1,012 newborn samples from retrospective TBS. Three independent groups performed the study under strict double-blind conditions according to the screening modes: independent biochemical (IBS), independent NeoSeq (INS), sequential (SS), and combined (CS) screening. Using targeted sequencing, the NeoSeq panel included 154 pathogenic genes covering 86 diseases.</p></div><div><h3>Results</h3><p>Of the 1,012 newborns, 120 were diagnosed were diagnosed with genetic diseases Among them, 52 cases were within the scope of TBS and 68 additional cases were identified through nGS. The number of cases detected per screening mode was 50, 113, 56, and 119 for IBS, INS, SS, and CS, respectively. CS was the most satisfactory screening mode, with the detection rate of 99.17%, the specificity and positive predictive value of 100%, and the negative predictive value of 99.89%. In addition, of the 68 cases identified by nGS (96 variants in 31 pathogenic genes), only four participants (5.9%) had clinical manifestations consistent with the disease. The experimental reporting cycles of CS and INS were the shortest.</p></div><div><h3>Conclusions</h3><p>CS was the most satisfactory method for newborn screening, which combined nGS with TBS to improve early diagnosis.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139645465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CETP-derived Peptide Seq-1, the Key Component of HB-ATV-8 Vaccine Prevents Stress Responses, and Promotes Downregulation of Pro-Fibrotic Genes in Hepatocytes and Stellate Cells","authors":"Sandra Calixto-Tlacomulco ,&nbsp;Ismael Luna-Reyes ,&nbsp;Blanca Delgado-Coello ,&nbsp;Roxana Gutiérrez-Vidal ,&nbsp;Juan Pablo Reyes-Grajeda ,&nbsp;Jaime Mas-Oliva","doi":"10.1016/j.arcmed.2023.102937","DOIUrl":"10.1016/j.arcmed.2023.102937","url":null,"abstract":"<div><h3>Background</h3><p>The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis.</p></div><div><h3>Methods</h3><p>The HepG2 hepatoma-derived cell line was employed to establish an <em>in vitro</em> steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-β, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied.</p></div><div><h3>Aim</h3><p>To establish an <em>in vitro</em> steatosis model employing HepG2 cells that mimics molecular processes observed <em>in vivo</em> during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC.</p></div><div><h3>Results and Conclusion</h3><p>Peptide seq-1-treated HepG2 cells show a downregulation of <em>COLIA1, ACTA2</em>, and <em>TGF-β</em> genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0188440923001807/pdfft?md5=87256654d9a752b2f1d6ddb4a88b3dbb&pid=1-s2.0-S0188440923001807-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Intestinal Defensin 5 Ameliorates the Sensitization of Colonic Cancer Cells to 5-Fluorouracil","authors":"Anshul Panjeta ,&nbsp;Khushpreet Kaur ,&nbsp;Rinkle Sharma ,&nbsp;Indu Verma ,&nbsp;Simran Preet","doi":"10.1016/j.arcmed.2024.102966","DOIUrl":"10.1016/j.arcmed.2024.102966","url":null,"abstract":"<div><h3>Background and Aim</h3><p>The increasing dilemma of multidrug-resistant cancer cells in response to currently available chemotherapeutic drugs and their associated side effect(s), calls for the investigation of alternative anticancer advances and molecules. Therefore, the present study aimed to elucidate the combinatorial potential against colon cancer of human defensin 5 in combination with 5-fluorouracil (5-FU), and against 5-FU resistant colon tumor cells.</p></div><div><h3>Methods</h3><p>The <em>in vivo</em> combinatorial potential of HD-5 with 5-FU was elucidated in terms of tumor morphometrics, apoptosis assay, surface morphology histology of the colon(s), and transcriptional alterations. Changes in membrane dynamics with mucin expression were evaluated by fluorescence microscopy and histochemistry. The <em>in vitro</em> activity of the peptide/drug conjunction was explored by phase contrast microscopy, MTT, LDH assay, and AO/EtBr staining. Chemoresistance to 5-FU was determined by phase contrast microscopy, MTT assay, annexin V-FITC/PI flow cytometry, and MDR-1, Bak, and Bax expression.</p></div><div><h3>Results</h3><p><em>In vivo</em> decreases in tumor parameters, with a marked increase in apoptosis and neutrophil infiltrations indicated restoration of normal architecture with improved mucin content in the treated colons. This happened with substantial changes in key molecular markers of the intrinsic apoptotic cascade. Membrane dynamics revealed that peptides and chemotherapeutic drugs could bind to cancerous cells by taking advantage of altered levels of membrane fluidity.</p></div><div><h3>Conclusion</h3><p>Peptide treatment of drug-resistant Caco-2 cells promotes enhanced 5-FU uptake, in contrast to when cells were treated with 5-FU alone. Hence, HD-5 as an adjunct to 5-FU, exhibited strong cancer cell killing even against 5-FU-resistant tumorigenic cells.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Fibrate Treatment on Circulating Adipokine Levels: A Systematic Review and Meta-analysis of Randomized Clinical Trials","authors":"Luis E. Simental-Mendía ,&nbsp;Mario Simental-Mendía ,&nbsp;Amirhossein Sahebkar ,&nbsp;Stephen L. Atkin ,&nbsp;Tannaz Jamialahmadi","doi":"10.1016/j.arcmed.2024.102957","DOIUrl":"10.1016/j.arcmed.2024.102957","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Fibrates are widely used in the treatment of </span>dyslipidemia<span> and associated metabolic abnormalities; however, their effects on adipokines are unclear. Aim of the study. This meta-analysis of </span></span>clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels.</p></div><div><h3>Methods</h3><p>Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method.</p></div><div><h3>Results</h3><p>This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: –1.58 ng/mL, 95% CI: –2.96, –0.20, <em>p</em> = 0.02, <em>I²</em> = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: –13.86 ng/mL, 95% CI: –26.70, –1.03, <em>p</em> = 0.03, <em>I²</em><span> = 99%), and visfatin (WMD: –1.52 ng/mL, 95% CI: –2.49, –0.56, </span><em>p</em> = 0.002, <em>I²</em><span> = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: –0.69 µg/ml, 95% CI: –1.40, 0.02, </span><em>p</em> = 0.06, <em>I²</em><span> = 83%) and resistin (WMD: –2.27 ng/mL, 95% CI: –7.11, 2.57, </span><em>p</em> = 0.36, <em>I²</em> = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1.</p></div><div><h3>Conclusion</h3><p>This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}