Pub Date : 2024-10-19DOI: 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.
{"title":"Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma.","authors":"Florian Weber, Kirsten Utpatel, Katja Evert, Thomas S Weiss, Christa Buechler","doi":"10.3390/biomedicines12102397","DOIUrl":"10.3390/biomedicines12102397","url":null,"abstract":"<p><strong>Background/objectives: </strong>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.</p><p><strong>Methods: </strong>Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</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/PMC11504530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494274","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}
Pub Date : 2024-10-19DOI: 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。
{"title":"Effects of Far-Infrared Rays Emitted from Loess Bio-Balls on Lymphatic Circulation and Reduction of Inflammatory Fluids.","authors":"Yong Il Shin, Min Seok Kim, Yeong Ae Yang, Gye Rok Jeon, Jae Ho Kim, Yeon Jin Choi, Woo Cheol Choi, Jae Hyung Kim","doi":"10.3390/biomedicines12102392","DOIUrl":"10.3390/biomedicines12102392","url":null,"abstract":"<p><p><b>Background</b>: 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. <b>Method</b>: Subjects in group A (<i>n</i> = 27) were exposed to FIR emitted from a loess bio-ball mat set at 40 °C for 30 min, and subjects in group B (<i>n</i> = 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. <b>Results</b>: 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. <b>Conclusions</b>: FIR emitted from loess bio-balls activates biological tissues and lymphatic circulation, gradually reducing the levels of inflammatory fluids over time.</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/PMC11504071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494222","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}
Pub Date : 2024-10-19DOI: 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.
{"title":"<i>ABCG2</i> Gene Expression in Non-Small Cell Lung Cancer.","authors":"Agnieszka Jeleń, Marta Żebrowska-Nawrocka, Mariusz Łochowski, Dagmara Szmajda-Krygier, Ewa Balcerczak","doi":"10.3390/biomedicines12102394","DOIUrl":"10.3390/biomedicines12102394","url":null,"abstract":"<p><p><b>Background/Objectives:</b> 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 <i>ABCG2</i> 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 <i>ABCG2</i> expression in blood of NSCLC patients. <b>Methods:</b> 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. <b>Results:</b> The <i>ABCG2</i> gene was expressed at a low level in NSCLC, and did not correlate with clinical aggressiveness of lung cancer. Higher <i>ABCG2</i> 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 <i>ABCG2</i> 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. <b>Conclusions:</b> 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.</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/PMC11504646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494177","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}
Pub Date : 2024-10-19DOI: 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。
{"title":"Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the <i>ATXN2</i> Gene.","authors":"Anna Dorohova, Oksana Lyasota, Stepan Dzhimak, Alexandr Svidlov, Olga Leontyeva, Mikhail Drobotenko","doi":"10.3390/biomedicines12102396","DOIUrl":"10.3390/biomedicines12102396","url":null,"abstract":"<p><p><b>Background:</b> 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 <i>ATXN2</i> 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. <b>Methods:</b> In this work, the influence of the viscosity of the medium and the external torque on the stability of the CAG tract in the <i>ATXN2</i> gene was studied using mathematical modeling methods. <b>Results:</b> 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. <b>Conclusions:</b> 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.</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/PMC11504642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494269","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}
Pub Date : 2024-10-19DOI: 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.
{"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}
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.
{"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}
Pub Date : 2024-10-18DOI: 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}
Pub Date : 2024-10-18DOI: 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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"title":"Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis.","authors":"Teresa Soda, Teresa Pasqua, Giovambattista De Sarro, Francesco Moccia","doi":"10.3390/biomedicines12102387","DOIUrl":"10.3390/biomedicines12102387","url":null,"abstract":"<p><p>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.</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/PMC11504205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494178","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}
Pub Date : 2024-10-18DOI: 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.
{"title":"<i>ABCA3</i> 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.","authors":"Maria Livia Ognean, Mădălina Anciuc-Crauciuc, Radu Galiș, Alex-Emilian Stepan, Mioara Desdemona Stepan, Claudia Bănescu, Florin Grosu, Boris W Kramer, Manuela Cucerea","doi":"10.3390/biomedicines12102390","DOIUrl":"10.3390/biomedicines12102390","url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Material and Methods:</b> A family case report was conducted; targeted panel genetic testing identified a variant of the <i>SFTPB gene</i> and two variants of <i>ABCA3</i> genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two <i>ABCA3</i> 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. <b>Results:</b> The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the <i>SFTPB</i> p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two <i>ABCA3</i> 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. <b>Conclusions:</b> 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.</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/PMC11505159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494176","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}