Brazilian Journal of Medical and Biological Research最新文献_第4页

A clinical drug-drug interaction assessment using physiologically based pharmacokinetic modeling: a case study with chloroquine and colchicine. 使用基于生理的药代动力学模型的临床药物-药物相互作用评估：氯喹和秋水仙碱的案例研究。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15326

T R Maciel, F E G Teixeira, I C Bitencourt, C O Pacheco, S E Haas

{"title":"A clinical drug-drug interaction assessment using physiologically based pharmacokinetic modeling: a case study with chloroquine and colchicine.","authors":"T R Maciel, F E G Teixeira, I C Bitencourt, C O Pacheco, S E Haas","doi":"10.1590/1414-431X2026e15326","DOIUrl":"10.1590/1414-431X2026e15326","url":null,"abstract":"The combination of drugs for malaria treatment holds promise, although the potential for drug-drug interactions remains insufficiently explored in novel therapeutic combinations. This study aims to assess these interactions using physiologically based pharmacokinetic modeling, supported by data-driven parameter optimization, as a step towards the preclinical development of a formulation containing chloroquine and colchicine. Given that both compounds share metabolic pathways involving CYP3A4 and CYP2D6, we developed individual and population models using a middle-out strategy in PK-Sim®, an open-source software, and validated these models by comparing predicted and observed pharmacokinetic parameters. Simulations evaluated competitive inhibition between the compounds. The results indicated no significant changes in systemic exposure, with the area under the curve and maximum concentration values remaining consistent between single and combined administration. Our findings suggest that the proposed modeling is a powerful tool for predicting pharmacokinetic interactions during the preformulation stage, offering mechanistic insight and supporting rational decision-making prior to in vivo studies. The absence of significant drug-drug interactions between chloroquine and colchicine reinforces the feasibility of advancing this combination in future therapeutic development.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15326"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13362891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZNF821 as a potential biomarker associated with immune infiltration in pancreatic adenocarcinoma. ZNF821作为胰腺腺癌免疫浸润相关的潜在生物标志物

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e14584

Xiaocang Ren, Yanyan Ma, Jing Li, Yuee Liu, Zhihong Qiu

{"title":"ZNF821 as a potential biomarker associated with immune infiltration in pancreatic adenocarcinoma.","authors":"Xiaocang Ren, Yanyan Ma, Jing Li, Yuee Liu, Zhihong Qiu","doi":"10.1590/1414-431X2026e14584","DOIUrl":"10.1590/1414-431X2026e14584","url":null,"abstract":"Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy originating from the epithelial cells lining the pancreatic ducts. To date, no robust biomarkers have been established to reliably predict PAAD prognosis. To identify potential transcriptional biomarkers, we analyzed transcription factor expression in PAAD patients from The Cancer Genome Atlas (TCGA) and identified ZNF821 as a novel prognostic marker. Higher ZNF821 expression was significantly associated with improved patient survival and was positively correlated with increased immune infiltration and cytotoxic activity within the tumor microenvironment. Additionally, elevated ZNF821 levels predicted a favorable response to immunotherapy. We further discovered that tumors downregulate ZNF821 through DNA methylation, facilitating immune evasion during tumor progression. To investigate its functional mechanisms, we analyzed proteins regulated by or interacting with ZNF821. Moreover, we identified existing drugs that may target ZNF821, suggesting potential therapeutic applications for PAAD. Experimental validation using RT-PCR confirmed ZNF821 downregulation in pancreatic cancer cell lines. Furthermore, tumor growth comparisons between ZNF821-overexpressing and ZNF821-null models demonstrated that ZNF821 enhances anti-tumor immunity, contributing to tumor suppression. In summary, our study identified ZNF821 as a novel prognostic biomarker in PAAD, offering new insights into tumor immune evasion and potential therapeutic strategies.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e14584"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13362889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Zingerone alleviates diabetic nephropathy by interrupting the ER stress-inflammation-apoptosis cascade in streptozotocin-induced diabetic mice. 姜酮通过阻断链脲佐菌素诱导的糖尿病小鼠内质网应激-炎症-凋亡级联减轻糖尿病肾病。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-03 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15216

Bi Ke, Xiaojing Xiong, Chen Wang, Xiuyuan Feng, Hua Yan, Wenfeng Wang, Guang Xu

{"title":"Zingerone alleviates diabetic nephropathy by interrupting the ER stress-inflammation-apoptosis cascade in streptozotocin-induced diabetic mice.","authors":"Bi Ke, Xiaojing Xiong, Chen Wang, Xiuyuan Feng, Hua Yan, Wenfeng Wang, Guang Xu","doi":"10.1590/1414-431X2026e15216","DOIUrl":"10.1590/1414-431X2026e15216","url":null,"abstract":"Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of diabetic nephropathy. In this study, we aimed to investigate the protective effects of zingerone on the kidney and elucidate the underlying mechanisms in streptozotocin (STZ)-induced diabetic mice. Diabetic mice were randomly assigned to three groups: untreated control, diabetic control, and STZ+zingerone-treated group. Over a 3-month period, we monitored body weight, blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urinary protein (UP) excretion levels, and 24-h urinary volume (UV). Renal injury, apoptosis, inflammation, and ER stress were evaluated using histopathology, TUNEL staining, reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence. In vitro, mouse glomerular mesangial cells were exposed to high glucose, with or without zingerone or the ER stress inhibitor phenylbutyric acid (PBA). Thereafter, the expression levels of ER stress markers (CHOP and GRP78), inflammatory factors (NF-κB and TGF-β1), and apoptotic indices were assessed. Diabetic mice exhibited significantly elevated BG, BUN, SCR, 24-h UP, and ER stress marker levels, along with increased 24-h UV, renal apoptosis, and inflammation. Zingerone treatment significantly mitigated these parameters and improved renal pathological manifestations. In vitro, both zingerone and PBA effectively suppressed high glucose-induced ER stress, inflammation, and apoptosis in mesangial cells. These findings demonstrated that zingerone attenuated diabetic renal injury through inhibition of ER stress-related pathways and downstream inflammation, thereby underscoring its potential as a therapeutic candidate for diabetic nephropathy.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15216"},"PeriodicalIF":1.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pulmonary infection by non-tuberculous mycobacteria in an endemic region for tuberculosis in Northeast Brazil. 巴西东北部结核病流行地区的非结核分枝杆菌肺部感染。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-03 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15340

A S Lima, W H V Carvalho-Silva, K M Gomes, R S Duarte, C F Luna, H C Schindler, L M L Montenegro

{"title":"Pulmonary infection by non-tuberculous mycobacteria in an endemic region for tuberculosis in Northeast Brazil.","authors":"A S Lima, W H V Carvalho-Silva, K M Gomes, R S Duarte, C F Luna, H C Schindler, L M L Montenegro","doi":"10.1590/1414-431X2026e15340","DOIUrl":"10.1590/1414-431X2026e15340","url":null,"abstract":"A wide range of non-tuberculous mycobacteria (NTM) species have been identified worldwide, with increasing recognition of their clinical importance in pulmonary disease. To evaluate the diversity, frequency, antimicrobial resistance profile, and clinical characteristics of pulmonary NTM cases in Pernambuco, Brazil, we conducted a descriptive clinical-epidemiological and comparative cross-sectional study of pulmonary NTM (PNTM) along with pulmonary tuberculosis (PTB). Pulmonary biological samples were obtained and analyzed by bacilloscopy, culture, and biochemical tests for PNTM and PTB diagnosis. Molecular analysis for hsp65 and rpoB genes was also performed to confirm NTM species and classified as slowly growing mycobacteria (SGM) or rapidly growing mycobacteria (RGM). Antimicrobial susceptibility tests were also performed with 13 different drugs. Twenty-one PNTM cases were identified. They were significantly associated with a previous history of TB (66.7%) and occurred more frequently in males (67.7%). The age of the PNTM group (52.0±14.7 years) was significantly higher than PTB group (44.0±14.8 years; P=0.006). Six different NTM species were detected (three SGM and three RGM): M. kansasii (57.1%), M. intracellulare (9.5%), M. abscessus subsp. abscessus (9.5%), M. abscessus subsp. bolletii (9.5%), M. fortuitum (9.5%), and M. asiaticum (4.8%). Among the cases, 15 specimens demonstrated antimicrobial resistance to at least one drug. This is the first study to describe the frequency, diversity, and antimicrobial resistance of NTM species associated with pulmonary disease in Pernambuco, providing relevant epidemiological data to support diagnosis and management in this endemic region for tuberculosis.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15340"},"PeriodicalIF":1.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Helicobacter pylori outer membrane vesicle-induced hsa-miR-302a-3p and hsa-miR-184 promote the occurrence and development of gastric cancer. 幽门螺杆菌外膜囊泡诱导的hsa-miR-302a-3p和hsa-miR-184促进胃癌的发生发展。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-03 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15191

Yang Wen, Xiaoqing Deng, Sisi Wei, Yanlei Ge, Xiaoya Li, Zhirong Li, Lianmei Zhao, Guogui Sun

{"title":"Helicobacter pylori outer membrane vesicle-induced hsa-miR-302a-3p and hsa-miR-184 promote the occurrence and development of gastric cancer.","authors":"Yang Wen, Xiaoqing Deng, Sisi Wei, Yanlei Ge, Xiaoya Li, Zhirong Li, Lianmei Zhao, Guogui Sun","doi":"10.1590/1414-431X2026e15191","DOIUrl":"10.1590/1414-431X2026e15191","url":null,"abstract":"Helicobacter pylori (H. pylori) is a major gastric cancer pathogen. Recent studies have linked H. pylori infection to microRNA (miRNA) dysregulation. H. pylori outer membrane vesicles (OMVs) support bacterial survival and pathogenesis, but the OMV-miRNA interactions remain unclear. To address this lack of understanding, we co-cultured the H. pylori strain NCTC11637 and its OMVs with the gastric epithelial cell line GES-1 and gastric cancer cell lines SGC-7901 and HGC-27. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed hsa-miR-302a-3p upregulation in the GES-1 line and hsa-miR-184 upregulation in the SGC-7901 and HGC-27 lines. To explore the OMV-miRNA mechanisms, we built transfected models: GES-1 with hsa-miR-302a-3p overexpression and SGC-7901 and HGC-27 with hsa-miR-184 overexpression or inhibition. The experimental study on the malignant behavior of tumors (i.e., proliferation, migration, invasion, and clonogenic assay) showed enhanced malignant phenotypes in the overexpressed cells. Hsa-miR-184 inhibition reversed these effects in the cancer cells. Intriguingly, hsa-miR-302a-3p overexpression in the GES-1 cells enhanced tumorigenesis via anchorage-independent growth, which is a key carcinogenic trait. Next, we identified differential proteins in the overexpressed cells via proteomic mass spectrometry. Finally, we validated the target proteins and analyzed the signaling pathways to elucidate the mechanisms. We found that H. pylori OMV-induced hsa-miR-302a-3p upregulation may promote gastric cancer initiation, while hsa-miR-184 overexpression may drive progression. This study provides a basis for the diagnosis and treatment of gastric cancer.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15191"},"PeriodicalIF":1.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporal heterogeneity of gestational syphilis in the 1st Health Region of Pará in the Brazilian Amazon. 巴西亚马逊地区par<s:1>第一卫生区妊娠期梅毒的时空异质性

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-07-03 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15574

K R Silva, R G Silva, R J P S Guimarães, C R Mesquita, L M V Nogueira, M E C Rassy

{"title":"Spatiotemporal heterogeneity of gestational syphilis in the 1st Health Region of Pará in the Brazilian Amazon.","authors":"K R Silva, R G Silva, R J P S Guimarães, C R Mesquita, L M V Nogueira, M E C Rassy","doi":"10.1590/1414-431X2026e15574","DOIUrl":"10.1590/1414-431X2026e15574","url":null,"abstract":"Syphilis in pregnant women remains an important public health problem in Brazil, especially in urban contexts marked by social inequalities and weaknesses in the organization of health services. In the Amazon region, territorial, socioeconomic, and healthcare-related characteristics influence access to prenatal care, timely diagnosis, and the control of vertical transmission. Thus, this study aimed to analyze the spatiotemporal patterns of syphilis among pregnant women in a health region of the Brazilian Amazon. This is an ecological, descriptive, and quantitative study that evaluated 5,607 positive cases of syphilis in pregnant women residing in the 1st Health Region (Metropolitan I) of Pará, composed of Belém, Ananindeua, Marituba, Benevides, and Santa Bárbara, reported between 2019 and 2024. Data were obtained from the Pará State Health Department, and the \"geocodebr\" package from the National Institute for Space Research and the R software were used for georeferencing the geographic coordinates of each case. Kernel Density Estimation analysis identified the presence of high-density clusters in the 2019-2020 and 2023-2024 biennia. Spatial scan analysis identified Marituba as a significant cluster, indicating higher risk and a constant concentration of cases throughout the analyzed period. Syphilis in pregnant women presents a heterogeneous and persistent spatiotemporal pattern in the region, requiring integrated, territorialized, and intersectoral strategies.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15574"},"PeriodicalIF":1.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RETRACTION: Differential expression of microRNA-411 and 376c is associated with hypertension in pregnancy. 缩回：microRNA-411和376c的差异表达与妊娠期高血压有关。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-06-05 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2025e7546retraction

Hui-Li Yang, Hong-Zhi Zhang, Fan-Rong Meng, Shu-Yi Han, Miao Zhang

引用次数: 0

RETRACTION: NOP14 inhibits melanoma proliferation and metastasis by regulating Wnt/β-catenin signaling pathway. 结论：NOP14通过调节Wnt/β-catenin信号通路抑制黑色素瘤的增殖和转移。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-06-05 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2025e7952retraction

Jingrong Li, Ruihua Fang, Jianqin Wang, Liehua Deng

引用次数: 0

RETRACTION: Comparison of two treatments for dry eye disease after corneal refractive surgery. 角膜屈光手术后干眼症两种治疗方法的比较。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-06-05 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2025e14754retraction

Yiping Ma, Yukun Yang

引用次数: 0

Knockout of Mucin 1 inhibits the proliferation, migration, and invasion of human MDA-MB-231 cells by blocking autophagy flow. 敲除Mucin 1通过阻断自噬流抑制人MDA-MB-231细胞的增殖、迁移和侵袭。

IF 1.9 4区医学

Brazilian Journal of Medical and Biological Research Pub Date : 2026-04-27 eCollection Date: 2026-01-01 DOI: 10.1590/1414-431X2026e15075

Zhimei Huang, Jiayao Zhao, Qinqin Zhang, Yu Luo, Wenqing Chen, Zhengchun Liu, Xiuli Liu

{"title":"Knockout of Mucin 1 inhibits the proliferation, migration, and invasion of human MDA-MB-231 cells by blocking autophagy flow.","authors":"Zhimei Huang, Jiayao Zhao, Qinqin Zhang, Yu Luo, Wenqing Chen, Zhengchun Liu, Xiuli Liu","doi":"10.1590/1414-431X2026e15075","DOIUrl":"10.1590/1414-431X2026e15075","url":null,"abstract":"To investigate the effects of Mucin 1 (MUC1) in human triple-negative breast cancer MDA-MB-231cells, the MDA-MB-231 cell line with MUC1 knockout (231-MUC1-KO) was constructed by CRISPR/Cas9 gene editing. Cell proliferation was evaluated using EDU and colony formation assays, and cell migration and invasion were detected by transwell assay. Autophagy flow was assessed by western blot and Ad-mCherry-GFP-LC3B dual-fluorescence system and validated by lysosome inhibitor barfimycin A1 and autophagy inducer rapamycin. Key proteins of autophagosomes and lysosomal fusion (STXl7, SNAP29) and lysosomal tagged protein (LAMP1) were detected by western blot, and lysosomal pH was evaluated by Lysotracker Red fluorescence. MUC1 expression was low in human normal breast epithelial cells MCF-10A, but was highly expressed in human MDA-MB-231 cells and tissues. Successful MUC1 knockout was confirmed by gene sequencing, RT-qPCR, and western blot. Loss of MUC1 gene expression in 231-MUC1-KO significantly reduced proliferation, migration, and invasion. Compared with the control group, MUC1 knockout led to a significant increase of autophagy-related proteins LC3-II and p62, which is consistent with the effect of lysosome inhibitor bleomycin A1. After adding the autophagy inducer rapamycin, compared with the control group, the accumulation of LC3-II and p62 proteins also further increased. The expression level of LAMP1 was downregulated and the lysosome pH increased, but the expression levels of STXl7 and SNAP29 were not affected. These findings suggest that MUC1 promotes malignant behaviors in MDA-MB-231 cells by regulating autophagic flow, likely through lysosomal dysfunction-mediated autophagy blockade.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":"59 ","pages":"e15075"},"PeriodicalIF":1.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0