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Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma. 丙型肝炎患者肝脏骨形态发生蛋白和激活素膜结合抑制因子水平下降,但与肝细胞癌的进展无关。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-19 DOI: 10.3390/biomedicines12102397
Florian Weber, Kirsten Utpatel, Katja Evert, Thomas S Weiss, Christa Buechler

Background/objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages.

Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients.

Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues.

Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.

背景/目的:骨形态发生蛋白和激活素膜结合抑制剂(BAMBI)是转化生长因子(TGF)-β 1 型信号传导的拮抗剂。BAMBI 是一种抗纤维化蛋白,具有促癌和抗癌活性。我们的研究旨在将肝细胞癌(HCC)中肝细胞 BAMBI 蛋白水平与 T 分期、淋巴结侵犯、血管侵犯、分级、肿瘤大小和国际癌症控制联盟(UICC)分期以及肝脏炎症和纤维化分期相关联:结果:在全组HCC组织和性别特异性分析中,BAMBI蛋白与T分期、血管侵犯、淋巴结侵犯、组织学分级、UICC分期和肿瘤大小无关。因此,BAMBI与总生存率、无复发生存率和无转移生存率无关。肿瘤和非肿瘤组织中的BAMBI蛋白水平与炎症和纤维化分级无关。通过免疫印迹法分析一小批HCC患者的HCC组织和非肿瘤组织中的BAMBI蛋白水平,以及通过免疫组化法分析上述患者的组织中的BAMBI蛋白水平,结果显示两者相似。值得注意的是,与疾病严重程度相当的乙型肝炎病毒(HBV)感染者相比,丙型肝炎病毒(HCV)感染者的 HCC 组织中 BAMBI 蛋白含量较低。免疫印迹分析显示,与 HBV 患者和正常人肝组织相比,HCV 患者非肿瘤组织中的 BAMBI 蛋白减少:总之,这项分析表明,HCC 患者的肝细胞 BAMBI 蛋白水平与 HCV 感染有关,而与基础肝病的严重程度和癌症分期无关。
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引用次数: 0
Effects of Far-Infrared Rays Emitted from Loess Bio-Balls on Lymphatic Circulation and Reduction of Inflammatory Fluids. 黄土生物球发射的远红外线对淋巴循环和减少炎性体液的影响
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-19 DOI: 10.3390/biomedicines12102392
Yong Il Shin, Min Seok Kim, Yeong Ae Yang, Gye Rok Jeon, Jae Ho Kim, Yeon Jin Choi, Woo Cheol Choi, Jae Hyung Kim

Background: FIR therapy is used in various medical settings to treat diseases associated with inflammation and edema. Unlike conventional FIR lamp therapy, this study investigated how body fluids change depending on the intensity and duration of FIR irradiation to the whole body. Method: Subjects in group A (n = 27) were exposed to FIR emitted from a loess bio-ball mat set at 40 °C for 30 min, and subjects in group B (n = 27) were exposed to FIR emitted from a loess bio-ball mat set at 30 °C for 7 h during sleep. Changes in bioimpedance parameters and fluid-related values were measured using a body fluid analyzer before and after exposure to FIR. Results: Changes in bioimpedance parameters associated with inflammatory fluids were quantitatively confirmed. In group A, there was a minimal change in fluid-related measurements. However, significant changes in bioimpedance parameters associated with inflammatory fluids were observed in group B exposure to FIR for 7 h during sleep. Conclusions: FIR emitted from loess bio-balls activates biological tissues and lymphatic circulation, gradually reducing the levels of inflammatory fluids over time.

背景:各种医疗机构都在使用红外线疗法治疗与炎症和水肿有关的疾病。与传统的红外灯疗法不同,本研究调查了体液如何随红外对全身照射的强度和持续时间而变化。研究方法A组受试者(n = 27)在睡眠中接受40 °C黄土生物球垫发出的红外线照射30分钟,B组受试者(n = 27)在睡眠中接受30 °C黄土生物球垫发出的红外线照射7小时。在暴露于红外线前后,使用体液分析仪测量了生物阻抗参数和体液相关值的变化。结果显示与炎性体液相关的生物阻抗参数变化得到了定量证实。在 A 组中,体液相关测量值的变化极小。然而,在 B 组中,在睡眠期间暴露于红外辐射 7 小时后,与炎性体液相关的生物阻抗参数发生了重大变化。结论黄土生物球发出的红外线可激活生物组织和淋巴循环,随着时间的推移逐渐降低炎性体液的水平。
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引用次数: 0
ABCG2 Gene Expression in Non-Small Cell Lung Cancer. 非小细胞肺癌中的 ABCG2 基因表达
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-19 DOI: 10.3390/biomedicines12102394
Agnieszka Jeleń, Marta Żebrowska-Nawrocka, Mariusz Łochowski, Dagmara Szmajda-Krygier, Ewa Balcerczak

Background/Objectives: ATP-binding cassette subfamily G member 2 [ABCG2/breast cancer resistance protein (BCRP)] contributes to mechanisms of multidrug resistance (MDR) and is a marker of side population (SP) cells in human cancers. The primary objective of this study was to investigate the impact of ABCG2 gene expression on the non-small cell lung cancer (NSCLC) development, course of cancer disease, and patient prognosis using publicly available data. Obtained results were supplemented with assessment of ABCG2 expression in blood of NSCLC patients. Methods: The dataset of lung cancer was analyzed utilizing the TIMER 2.0, UALCAN, TNMplot, MEXPRESS, cBioPortal, MethSurv, KM Plotter, STRING, and ShinyGO 0.80 databases. Blood samples from 50 patients were assessed using the real-time PCR method. Results: The ABCG2 gene was expressed at a low level in NSCLC, and did not correlate with clinical aggressiveness of lung cancer. Higher ABCG2 expression improved overall survival, but only in LUAD. In addition, CpG sites located on the CpG island affecting the NSCLC patient's prognosis were indicated. In the case of our own laboratory results, the study did not reveal any changes in the ABCG2 expression levels in blood collected from patients at different time points during the diagnostic-therapeutic procedure. In the in silico analysis, most ABCG2 protein interactors were associated with the development of drug resistance. Conclusions: ABCG2 appears to have a particularly significant impact on the survival of patients with lung cancer and on the effect of immunotherapy related to immune cell infiltration. Presented findings may support personalized medicine strategies based on bioinformatics findings.

背景/目的:ATP结合盒G亚家族成员2[ABCG2/乳腺癌耐药蛋白(BCRP)]有助于多药耐药(MDR)机制,是人类癌症中侧群细胞(SP)的标记物。本研究的主要目的是利用公开数据调查 ABCG2 基因表达对非小细胞肺癌(NSCLC)发展、癌症病程和患者预后的影响。此外,还评估了非小细胞肺癌患者血液中 ABCG2 的表达情况。研究方法利用 TIMER 2.0、UALCAN、TNMplot、MEXPRESS、cBioPortal、MethSurv、KM Plotter、STRING 和 ShinyGO 0.80 数据库分析肺癌数据集。采用实时 PCR 方法对 50 名患者的血样进行了评估。结果显示ABCG2基因在NSCLC中的表达水平较低,与肺癌的临床侵袭性无关。ABCG2的高表达可提高总生存率,但仅适用于LUAD。此外,位于 CpG 岛上影响 NSCLC 患者预后的 CpG 位点也被指出。就我们自己的实验室结果而言,研究并未发现在诊断-治疗过程中不同时间点采集的患者血液中 ABCG2 表达水平有任何变化。在硅分析中,大多数 ABCG2 蛋白相互作用因子与耐药性的产生有关。结论:ABCG2ABCG2 似乎对肺癌患者的生存以及与免疫细胞浸润相关的免疫疗法的效果有特别重要的影响。这些发现可支持基于生物信息学发现的个性化医疗策略。
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引用次数: 0
Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the ATXN2 Gene. 介质粘度的波动可能会影响 ATXN2 基因中 CAG 片段的稳定性
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-19 DOI: 10.3390/biomedicines12102396
Anna Dorohova, Oksana Lyasota, Stepan Dzhimak, Alexandr Svidlov, Olga Leontyeva, Mikhail Drobotenko

Background: Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of the ATXN2 gene remains relevant. Previously, it was shown that the frequency of occurrence of additional OS (open states) zones increases with increasing length of the CAG tract, and the value inverse to the frequency correlates with the age of disease onset. Methods: In this work, the influence of the viscosity of the medium and the external torque on the stability of the CAG tract in the ATXN2 gene was studied using mathematical modeling methods. Results: It has been established that the probability of the appearance of additional OS zones of significant size increases with an increase in the CAG of the tract (k > 40 CAG repeats) for all viscosity values, however, at k ≤ 40, the change in viscosity does not significantly affect the probability of additional OS zones in the tract. Conclusions: It was found that under normal conditions (absence of pathology), viscosity does not have a reliable effect on the stability of the DNA molecule, but when pathology appears, an increase in viscosity contributes to an increase in DNA stability, and, accordingly, a decrease has a negative effect on the stabilization of the DNA molecule. In the zone of close to incomplete penetrance of the disease, viscosity does not have a reliable effect on the stability of the CAG tract.

背景:三核苷酸重复序列是许多目前无法治愈的神经退行性疾病的病因。在这方面,ATXN2 基因 CAG 道中重复序列的扩增导致疾病发生的原因以及预防或治疗方法的问题仍然具有现实意义。以前的研究表明,附加 OS(开放状态)区的发生频率随着 CAG 道长度的增加而增加,频率的倒数值与发病年龄相关。方法:本研究采用数学建模方法研究了介质粘度和外部扭矩对 ATXN2 基因 CAG 道稳定性的影响。结果:结果表明,在所有粘度值下,随着CAG束的增加(k > 40 CAG重复序列),出现相当大的额外OS区的概率也会增加,但是,当k ≤ 40时,粘度的变化对CAG束中出现额外OS区的概率没有显著影响。结论研究发现,在正常情况下(无病变),粘度对 DNA 分子的稳定性没有可靠的影响,但当出现病变时,粘度的增加会促进 DNA 稳定性的提高,相应地,粘度的降低会对 DNA 分子的稳定产生负面影响。在疾病的接近不完全渗透区,粘度对 CAG 道的稳定性没有可靠的影响。
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引用次数: 0
Circulating Serum Micro-RNA as Non-Invasive Diagnostic Biomarkers of Endometriosis. 作为子宫内膜异位症非侵入性诊断生物标志物的循环血清微 RNA。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-19 DOI: 10.3390/biomedicines12102393
Antonella Ravaggi, Cosetta Bergamaschi, Chiara Galbiati, Laura Zanotti, Aline S C Fabricio, Massimo Gion, Elia Cappelletto, Antonette E Leon, Massimo Gennarelli, Cesare Romagnolo, Giuseppe Ciravolo, Stefano Calza, Eliana Bignotti, Franco Odicino

Background/objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients.

Methods: RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs.

Results: One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling.

Conclusions: Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers.

背景/目的:子宫内膜异位症(END)是一种痛苦的妇科疾病。临床检查、影像学检查和腹腔镜检查可提供END的明确诊断。然而,非侵入性生物标志物有助于加强和简化诊断过程。微RNA(miRNA)是一种小型非编码RNA,可作为END的非侵入性生物标志物。本研究的目的是在一个女性回顾性队列中进行血清 miRNA 图谱分析,以确定与对照组患者相比,END 中表达不同的 miRNA:从67名END患者和60名对照组女性的血清样本中分离出RNA。用QuantStudio 12K Flex上的TaqMan OpenArray miRNA面板进行RT-qPCR,研究了754个miRNA面板的表达谱。miRNA 差异表达分析采用了删减回归模型。采用了几种基因富集算法来确定与差异表达的 miRNA 靶基因相关的通路:在END组或对照组至少75%的样本中检测到了130个miRNA。END组和对照组之间有16个miRNA发生了显著变化。富集分析发现,在与END相关的生物学过程中,包括炎症、血管生成、细胞侵袭、细胞周期/细胞增殖以及雌激素和孕激素荷尔蒙信号转导等众多通路中,靶标的代表性明显偏高:我们的研究表明,通过液体活检可以发现END患者和对照组之间表达不同的miRNA。我们的研究结果还表明,血清miRNA在END的病理生理学中具有潜在的作用,因此有必要对其作为非侵入性生物标记物进行进一步研究。
{"title":"Circulating Serum Micro-RNA as Non-Invasive Diagnostic Biomarkers of Endometriosis.","authors":"Antonella Ravaggi, Cosetta Bergamaschi, Chiara Galbiati, Laura Zanotti, Aline S C Fabricio, Massimo Gion, Elia Cappelletto, Antonette E Leon, Massimo Gennarelli, Cesare Romagnolo, Giuseppe Ciravolo, Stefano Calza, Eliana Bignotti, Franco Odicino","doi":"10.3390/biomedicines12102393","DOIUrl":"10.3390/biomedicines12102393","url":null,"abstract":"<p><strong>Background/objectives: </strong>Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients.</p><p><strong>Methods: </strong>RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs.</p><p><strong>Results: </strong>One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling.</p><p><strong>Conclusions: </strong>Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Mechanisms and Preventive Strategies for the Progression from Idiopathic Pulmonary Fibrosis to Lung Cancer: Insights from Transcriptomics and Genetic Factors. 探索特发性肺纤维化向肺癌发展的机制和预防策略:转录组学和遗传因素的启示。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.3390/biomedicines12102382
Kai Xie, Xiaoyan Tan, Zhe Chen, Yu Yao, Jing Luo, Haitao Ma, Yu Feng, Wei Jiang

Background: Idiopathic pulmonary fibrosis (IPF) leads to excessive fibrous tissue in the lungs, increasing the risk of lung cancer (LC) due to heightened fibroblast activity. Advances in nucleotide point mutation studies offer insights into fibrosis-to-cancer transitions. Methods: A two-sample Mendelian randomization (TSMR) approach was used to explore the causal relationship between IPF and LC. A weighted gene co-expression network analysis (WGCNA) identified shared gene modules related to immunogenic cell death (ICD) from transcriptomic datasets. Machine learning selected key genes, and a multi-layer perceptron (MLP) model was developed for IPF prediction and diagnosis. SMR and PheWAS were used to assess the expression of key genes concerning IPF risk. The impact of core genes on immune cells in the IPF microenvironment was explored, and in vivo experiments were conducted to examine the progression from IPF to LC. Results: The TSMR approach indicated a genetic predisposition for IPF progressing to LC. The predictive model, which includes eight ICD key genes, demonstrated a strong predictive capability (AUC = 0.839). The SMR analysis revealed that the elevated expression of MS4A4A was associated with an increased risk of IPF (OR = 1.275, 95% CI: 1.029-1.579; p = 0.026). The PheWAS did not identify any significant traits linked to MS4A4A expression. The rs9265808 locus in MS4A4A was identified as a susceptibility site for the progression of IPF to LC, with mutations potentially reprogramming lung neutrophils and increasing the LC risk. In vivo studies suggested MS4A4A as a promising therapeutic target. Conclusions: A causal link between IPF and LC was established, an effective prediction model was developed, and MS4A4A was highlighted as a therapeutic target to prevent IPF from progressing to LC.

背景:特发性肺纤维化(IPF)导致肺部纤维组织过多,由于成纤维细胞活性增强,增加了肺癌(LC)的风险。核苷酸点突变研究的进展有助于深入了解纤维化向癌症的转变。研究方法采用双样本孟德尔随机化(TSMR)方法探讨 IPF 与 LC 之间的因果关系。加权基因共表达网络分析(WGCNA)从转录组数据集中发现了与免疫原性细胞死亡(ICD)相关的共享基因模块。机器学习筛选出了关键基因,并开发出了用于预测和诊断 IPF 的多层感知器(MLP)模型。SMR和PheWAS用于评估与IPF风险有关的关键基因的表达。探讨了核心基因对 IPF 微环境中免疫细胞的影响,并进行了体内实验来研究 IPF 向 LC 的进展。结果:TSMR方法表明了IPF进展为LC的遗传易感性。预测模型包括八个 ICD 关键基因,显示出很强的预测能力(AUC = 0.839)。SMR分析显示,MS4A4A的表达升高与IPF风险增加有关(OR = 1.275,95% CI:1.029-1.579;p = 0.026)。PheWAS没有发现任何与MS4A4A表达相关的重要特征。MS4A4A中的rs9265808位点被确定为IPF进展为LC的易感位点,其突变可能使肺中性粒细胞重编程并增加LC风险。体内研究表明,MS4A4A 是一个很有前景的治疗靶点。结论建立了 IPF 和 LC 之间的因果联系,开发了有效的预测模型,并强调 MS4A4A 是防止 IPF 发展为 LC 的治疗靶点。
{"title":"Exploring the Mechanisms and Preventive Strategies for the Progression from Idiopathic Pulmonary Fibrosis to Lung Cancer: Insights from Transcriptomics and Genetic Factors.","authors":"Kai Xie, Xiaoyan Tan, Zhe Chen, Yu Yao, Jing Luo, Haitao Ma, Yu Feng, Wei Jiang","doi":"10.3390/biomedicines12102382","DOIUrl":"10.3390/biomedicines12102382","url":null,"abstract":"<p><p><b>Background:</b> Idiopathic pulmonary fibrosis (IPF) leads to excessive fibrous tissue in the lungs, increasing the risk of lung cancer (LC) due to heightened fibroblast activity. Advances in nucleotide point mutation studies offer insights into fibrosis-to-cancer transitions. <b>Methods:</b> A two-sample Mendelian randomization (TSMR) approach was used to explore the causal relationship between IPF and LC. A weighted gene co-expression network analysis (WGCNA) identified shared gene modules related to immunogenic cell death (ICD) from transcriptomic datasets. Machine learning selected key genes, and a multi-layer perceptron (MLP) model was developed for IPF prediction and diagnosis. SMR and PheWAS were used to assess the expression of key genes concerning IPF risk. The impact of core genes on immune cells in the IPF microenvironment was explored, and in vivo experiments were conducted to examine the progression from IPF to LC. <b>Results:</b> The TSMR approach indicated a genetic predisposition for IPF progressing to LC. The predictive model, which includes eight ICD key genes, demonstrated a strong predictive capability (AUC = 0.839). The SMR analysis revealed that the elevated expression of <i>MS4A4A</i> was associated with an increased risk of IPF (OR = 1.275, 95% CI: 1.029-1.579; <i>p</i> = 0.026). The PheWAS did not identify any significant traits linked to <i>MS4A4A</i> expression. The rs9265808 locus in <i>MS4A4A</i> was identified as a susceptibility site for the progression of IPF to LC, with mutations potentially reprogramming lung neutrophils and increasing the LC risk. In vivo studies suggested <i>MS4A4A</i> as a promising therapeutic target. <b>Conclusions:</b> A causal link between IPF and LC was established, an effective prediction model was developed, and <i>MS4A4A</i> was highlighted as a therapeutic target to prevent IPF from progressing to LC.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Definition Trans-Spinal Current Stimulation Improves Balance and Somatosensory Control: A Randomised, Placebo-Controlled Trial. 高清经脊髓电流刺激改善平衡和躯体感觉控制:随机安慰剂对照试验》。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.3390/biomedicines12102379
Teni Steingräber, Leon von Grönheim, Michel Klemm, Jan Straub, Lea Sasse, Jitka Veldema

Objectives: To investigate and compare the effects of three different high-definition (HD) non-invasive current stimulation (NICS) protocols on the spinal cord on support balance and somatosensory abilities in healthy young people.

Methods: Fifty-eight students were enrolled in this crossover study. All participants underwent application of (i) 1.5 mA anodal high-definition trans spinal direct current stimulation (HD-tsDCS), (ii) 1.5 mA cathodal HD-tsDCS, (iii) 1.5 mA high-definition trans spinal alternating current stimulation (HD-tsACS), and (iv) sham HD-tsDCS/ACS over the eighth thoracic vertebra in a randomised order. Balance (Y Balance test), deep sensitivity (Tuning Fork Test), and superficial sensitivity (Monofilament Test) of the lower limbs were tested immediately before and after each intervention.

Results: Balance ability improved significantly following anodal HD-tsDCS and HD-tsACS compared with that following sham HD-tsDCS/ACS. Similarly, deep sensitivity increased significantly with anodal HD-tsDCS and HD-tsACS compared to that with sham HD-tsDCS/ACS and cathodal HD-tsDCS. Furthermore, superficial sensitivity improved significantly following anodal HD-tsDCS compared with that after HD-tsACS and cathodal HD-tsDCS.

Conclusions: Our data show that HD-tsNICS effectively modulates the balance and somatosensory control of the lower limbs. Several diseases are associated with illness-induced changes in the spinal network in parallel with sensorimotor disabilities. Non-invasive spinal modulation may be a favourable alternative to conventional brain applications in rehabilitation. Future studies should therefore investigate these promising approaches among cohorts of patients with disabilities.

目的研究并比较三种不同的高清(HD)无创电流刺激(NICS)方案对脊髓的影响,以及对健康青少年平衡能力和躯体感觉能力的影响:方法:58 名学生参加了这项交叉研究。所有参与者都按照随机顺序在第八胸椎上接受了(i) 1.5 mA 阳极高清晰度跨脊髓直流电刺激(HD-tsDCS)、(ii) 1.5 mA 阴极高清晰度跨脊髓直流电刺激(HD-tsDCS)、(iii) 1.5 mA 高清晰度跨脊髓交变电流刺激(HD-tsACS)和(iv) 假 HD-tsDCS/ACS 的治疗。在每次干预前后立即测试下肢的平衡能力(Y 平衡测试)、深层灵敏度(音叉测试)和浅层灵敏度(单丝测试):结果:与假性 HD-tsDCS/ACS 相比,阳极 HD-tsDCS 和 HD-tsACS 治疗后的平衡能力明显提高。同样,与假 HD-tsDCS/ACS 和阴极 HD-tsDCS 相比,阳极 HD-tsDCS 和 HD-tsACS 的深部灵敏度明显提高。此外,与假HD-tsDCS/ACS和阴极HD-tsDCS相比,阳极HD-tsDCS后浅表敏感性明显提高:我们的数据表明,HD-tsNICS 能有效调节下肢的平衡和体感控制。有几种疾病与疾病引起的脊髓网络变化以及感觉运动障碍有关。在康复治疗中,非侵入性脊柱调节可能是传统脑部应用的一个有利替代方案。因此,未来的研究应在残疾患者群体中调查这些有前景的方法。
{"title":"High-Definition Trans-Spinal Current Stimulation Improves Balance and Somatosensory Control: A Randomised, Placebo-Controlled Trial.","authors":"Teni Steingräber, Leon von Grönheim, Michel Klemm, Jan Straub, Lea Sasse, Jitka Veldema","doi":"10.3390/biomedicines12102379","DOIUrl":"10.3390/biomedicines12102379","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate and compare the effects of three different high-definition (HD) non-invasive current stimulation (NICS) protocols on the spinal cord on support balance and somatosensory abilities in healthy young people.</p><p><strong>Methods: </strong>Fifty-eight students were enrolled in this crossover study. All participants underwent application of (i) 1.5 mA anodal high-definition trans spinal direct current stimulation (HD-tsDCS), (ii) 1.5 mA cathodal HD-tsDCS, (iii) 1.5 mA high-definition trans spinal alternating current stimulation (HD-tsACS), and (iv) sham HD-tsDCS/ACS over the eighth thoracic vertebra in a randomised order. Balance (Y Balance test), deep sensitivity (Tuning Fork Test), and superficial sensitivity (Monofilament Test) of the lower limbs were tested immediately before and after each intervention.</p><p><strong>Results: </strong>Balance ability improved significantly following anodal HD-tsDCS and HD-tsACS compared with that following sham HD-tsDCS/ACS. Similarly, deep sensitivity increased significantly with anodal HD-tsDCS and HD-tsACS compared to that with sham HD-tsDCS/ACS and cathodal HD-tsDCS. Furthermore, superficial sensitivity improved significantly following anodal HD-tsDCS compared with that after HD-tsACS and cathodal HD-tsDCS.</p><p><strong>Conclusions: </strong>Our data show that HD-tsNICS effectively modulates the balance and somatosensory control of the lower limbs. Several diseases are associated with illness-induced changes in the spinal network in parallel with sensorimotor disabilities. Non-invasive spinal modulation may be a favourable alternative to conventional brain applications in rehabilitation. Future studies should therefore investigate these promising approaches among cohorts of patients with disabilities.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Effects of VEGF-A and GSTM1/GSTT1 Variants in the Susceptibility to the Chronic Rhinosinusitis with Nasal Polyposis: A Pilot Genetic Study. VEGF-A和GSTM1/GSTT1变异在慢性鼻炎伴鼻息肉病易感人群中的影响:基因试验研究
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.3390/biomedicines12102383
Leandro Azevedo Camargo, Angela Adamski da Silva Reis, Stela Oliveira Rodrigues, Rodrigo da Silva Santos, Melissa Ameloti Gomes Avelino

Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphism in susceptibility to CRSwNP. A case-control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; p = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the GSTT1 present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP.

鼻息肉通常是慢性鼻炎伴鼻息肉病(CRSwNP)的一部分。然而,CRSwNP 的确切病因仍不清楚。此外,建议的病因包括感染、过敏和免疫紊乱,以及遗传易感性等。此外,还有研究认为,无氧自由基在鼻息肉的发病机制中起着重要作用,炎症细胞在吞噬过程中会产生自由基,这是由谷胱甘肽 S-转移酶(GST)系统控制的 ROS 的主要来源。虽然血管内皮生长因子(VEGF)在血管生成中起着重要作用,但它与炎症细胞的动员密切相关。这项试验性研究评估了遗传变异VEGF-A(rs28357093)和GSTM1/GSTT1缺失多态性与CRSwNP易感性之间的关联。研究人员对 61 名确诊为 CRSwNP 的患者和 100 名健康受试者进行了病例对照研究。分别通过 RFLP-PCR 和 SYBR Green 实时 PCR 对 VEGF-A (rs28357093) 和 GSTM1/GSTT1 缺失多态性进行了基因分型。具有 AC 基因型(rs28357093)的过敏性鼻炎携带者患 CRSwNP 的风险增加了 4 倍(OR = 4.20,95% CI = 1.31 至 13.50;p = 0.015)。这些证据表明,血管通透性增加可能会导致鼻腔发炎,从而引起广泛水肿和息肉生长。另一方面,每个基因变异都没有通过遗传模型验证其关联性。有趣的是,GSTT1 基因型对 CRSwNP 有保护作用。总之,在不同地区进行更大规模的研究可能有助于验证和评估遗传变异与 CRSwNP 之间的关联。
{"title":"The Effects of <i>VEGF-A</i> and <i>GSTM1</i>/<i>GSTT1</i> Variants in the Susceptibility to the Chronic Rhinosinusitis with Nasal Polyposis: A Pilot Genetic Study.","authors":"Leandro Azevedo Camargo, Angela Adamski da Silva Reis, Stela Oliveira Rodrigues, Rodrigo da Silva Santos, Melissa Ameloti Gomes Avelino","doi":"10.3390/biomedicines12102383","DOIUrl":"10.3390/biomedicines12102383","url":null,"abstract":"<p><p>Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant <i>VEGF-A</i> (rs28357093) and <i>GSTM1</i>/<i>GSTT1</i> deletion polymorphism in susceptibility to CRSwNP. A case-control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. <i>VEGF-A</i> (rs28357093) and <i>GSTM1</i>/<i>GSTT1</i> deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; <i>p</i> = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the <i>GSTT1</i> present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis. 心血管疾病的认知障碍和突触功能障碍:心脑轴的新前沿》。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.3390/biomedicines12102387
Teresa Soda, Teresa Pasqua, Giovambattista De Sarro, Francesco Moccia

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart-brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments.

在中枢神经系统中,突触可塑性是学习和记忆等过程的基础,主要由突触强度随活动而发生的变化驱动。这种可塑性通常表现为长期延时(LTP)和长期抑制(LTD),它们是对突触效能的双向调节。流行病学和实验的有力证据表明,神经和心血管疾病会严重损害心脑轴。尤其是心血管疾病,如心力衰竭、高血压、肥胖、糖尿病和胰岛素抵抗以及心律失常,可能会导致认知障碍,即所谓的心源性痴呆。在此,我们回顾了有关心源性痴呆可能产生的突触和分子机制的现有知识,并描述了心力衰竭、代谢综合征和心律失常是如何损害海马CA1区的LTP和/或LTD诱导和维持的。我们还讨论了新出现的证据,即内皮功能障碍可能会通过损害突触诱导的内皮一氧化氮合酶的激活来直接改变海马的 LTP。更好地了解心血管疾病如何影响中枢突触的正常功能,将为心源性痴呆的分子基础提供新的启示,从而为更具针对性的药物治疗提供新的视角。
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引用次数: 0
ABCA3 c.838C>T (p.Arg280Cys, R280C) and c.697C>T (p.Gln233Ter, Q233X, Q233*) as Causative Variants for RDS: A Family Case Study and Literature Review. ABCA3 c.838C>T(p.Arg280Cys,R280C)和 c.697C>T(p.Gln233Ter,Q233X,Q233*)作为 RDS 的致病变异体:一个家庭病例研究和文献综述。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.3390/biomedicines12102390
Maria Livia Ognean, Mădălina Anciuc-Crauciuc, Radu Galiș, Alex-Emilian Stepan, Mioara Desdemona Stepan, Claudia Bănescu, Florin Grosu, Boris W Kramer, Manuela Cucerea

Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature are inconsistent. Material and Methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, an analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

背景:呼吸窘迫综合征(RDS)是早产儿呼吸衰竭的主要原因,但也会影响5%-7%的足月儿。肺表面活性物质基因突变导致的肺表面活性物质代谢功能障碍是一种罕见疾病,从致命的新生儿 RDS 到与发病率和死亡率增加相关的间质性肺病不等。由于现有文献数据不一致,本研究旨在阐明在一个特定家族病例中发现的 ABCA3 变异的临床意义。材料和方法:进行了一个家族病例报告;有针对性的面板基因检测发现了 SFTPB 基因的一个变体和 ABCA3 基因的两个变体。通过对 PubMed、Google Scholar 数据库和基因组浏览器进行系统回顾等综合研究,明确了在该例患者身上发现的两个 ABCA3 基因变异的致病性。我们采用了先进的预测工具来评估这两个 ABCA3 变体的致病性,从而确保了我们研究结果的有效性和可靠性。结果指标病例表现为致命性新生儿 RDS。基因检测显示存在 SFTPB p.Val267Ile 变体,该变体以前没有报道过,但根据家族基因检测和病史,这是一个良性变体。此外,还发现了两个 ABCA3 基因变异:c.697C>T(尚未报道)和 c.838C>T。这些变异会影响 ABCA3 蛋白的功能,很可能与新生儿 RDS 有关。预测工具和文献中其他九个病例的数据都支持这一结论。结论:根据硅学预测因子、对该家族的分析以及文献中描述的病例,考虑将索引病例中发现的两个 ABCA3 变体重新分类为致病性/病原体是合理的。重新分类将提高遗传咨询的准确性并有助于正确诊断。
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引用次数: 0
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Biomedicines
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