Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.
{"title":"New treatment for osteoarthritis: Gene therapy.","authors":"Xinyu Li, Leyao Shen, Zhenghan Deng, Zeyu Huang","doi":"10.1093/pcmedi/pbad014","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad014","url":null,"abstract":"<p><p>Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/19/pbad014.PMC10273835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840308","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}
Jianbo Li, Qi Yang, Xinghong Gao, Feng Chen, Xinxia Gu, Xikun Zhou, Lei Chen, Jie Liu, Min Wu
Pseudomonas aeruginosa is an opportunistic Gr am-negativ e bac-terium that causes a series of life-threatening acute and/or c hr onic infections in humans, often in persons with immunode-ficiency . P . aeruginosa has been listed as one of the priority bacteria that r equir es extensiv e r esearc h and ur gent de v elopment of new antibiotic treatments by the World Health Organization ( WHO ) in 2017. 1 In r ecent years, numer ous studies have shown that miRNAs play an important role in infection and inflammatory responses. 2 , 3 Our earlier r esearc hes suggest that miRNAs are a k e y regulator of
{"title":"Overexpressed miR-539 exacerbates <i>Pseudomonas aeruginosa</i> puenmonia by promoting inflammatory responses.","authors":"Jianbo Li, Qi Yang, Xinghong Gao, Feng Chen, Xinxia Gu, Xikun Zhou, Lei Chen, Jie Liu, Min Wu","doi":"10.1093/pcmedi/pbad012","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad012","url":null,"abstract":"Pseudomonas aeruginosa is an opportunistic Gr am-negativ e bac-terium that causes a series of life-threatening acute and/or c hr onic infections in humans, often in persons with immunode-ficiency . P . aeruginosa has been listed as one of the priority bacteria that r equir es extensiv e r esearc h and ur gent de v elopment of new antibiotic treatments by the World Health Organization ( WHO ) in 2017. 1 In r ecent years, numer ous studies have shown that miRNAs play an important role in infection and inflammatory responses. 2 , 3 Our earlier r esearc hes suggest that miRNAs are a k e y regulator of","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/3b/pbad012.PMC10273829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9716788","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}
Background: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis.
Methods: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis.
Results: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05).
Conclusion: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.
{"title":"Investigating association between gut microbiota and sarcopenia-related traits: a Mendelian randomization study.","authors":"Jiaxi Zhao, Rui Liang, Quhong Song, Shiyu Song, Jirong Yue, Chenkai Wu","doi":"10.1093/pcmedi/pbad010","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad010","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis.</p><p><strong>Methods: </strong>To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis.</p><p><strong>Results: </strong><i>Alcaligenaceae, Family XIII</i>, and <i>Paraprevotella</i> were positively associated with the risk of low hand-grip strength (<i>P</i>-values < 0.05). <i>Streptococcaceae</i> were negatively associated with low hand-grip strength (<i>P</i>-values < 0.05). Eight bacterial taxa (<i>Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia</i>, and <i>Phascolarctobacterium)</i> were associated with a higher risk of ALM (<i>P</i>-values < 0.05). <i>Eubacterium fissicatena</i> group was negatively associated with ALM (<i>P</i>-values < 0.05).</p><p><strong>Conclusion: </strong>We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/47/pbad010.PMC10263384.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656055","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}
1 Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China 2 Clinical Trial Center , NMP A Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu 610041, China 3 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China 4 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China ∗Correspondence: Yongsheng Wang, wangys@scu.edu.cn §Yanna Lei and Shasha Zeng contributed equally to this work.
{"title":"Partial treatment response to alectinib in metastatic non-small cell lung cancer with KIDINS220-ALK fusion.","authors":"Yanna Lei, Shasha Zeng, Xiaoyu Li, Pei Shu, Weiya Wang, Yongsheng Wang","doi":"10.1093/pcmedi/pbad011","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad011","url":null,"abstract":"1 Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China 2 Clinical Trial Center , NMP A Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu 610041, China 3 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China 4 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China ∗Correspondence: Yongsheng Wang, wangys@scu.edu.cn §Yanna Lei and Shasha Zeng contributed equally to this work.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/d7/pbad011.PMC10251428.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612330","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}
Jiangyuan Zhou, Yuru Lan, Tong Qiu, Xue Gong, Zixin Zhang, Chunshui He, Qiang Peng, Fan Hu, Xuepeng Zhang, Guoyan Lu, Liqing Qiu, Feiteng Kong, Yongbo Zhang, Siyuan Chen, Yi Ji
Introduction: The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation.
Methods: The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors.
Results: A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis.
Conclusion: For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.
Kasabach-Merritt现象(KMP)是kaposiform血管内皮瘤(KHE)的严重并发症。KMP的危险因素需要进一步调查。方法:回顾KHE患者的病历资料。对KMP的危险因素采用单因素和多因素logistic回归模型,并采用受试者操作特征曲线下面积(receiver operator characteristic, ROC)评价危险因素的预测能力。结果:共纳入338例KHE患者。KMP的发生率为45.9%。发病年龄(P P P = 0.030, OR 2.428;95% CI 1.092-5.397),深度型(P = 0.010, OR 4.006;95% CI 1.389-11.556),纵隔或腹膜后病变位置(P = 0.019, or 11.864;通过多因素logistic回归,95% CI 1.497-94.003)与KMP发生相关。ROC曲线分析显示,发病年龄的最佳临界值为4.75个月(P P)。结论:对于发病年龄为5.35 cm的KHE患者,临床医生应警惕KMP的发生。建议积极治疗以改善预后。
{"title":"Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study.","authors":"Jiangyuan Zhou, Yuru Lan, Tong Qiu, Xue Gong, Zixin Zhang, Chunshui He, Qiang Peng, Fan Hu, Xuepeng Zhang, Guoyan Lu, Liqing Qiu, Feiteng Kong, Yongbo Zhang, Siyuan Chen, Yi Ji","doi":"10.1093/pcmedi/pbad008","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad008","url":null,"abstract":"<p><strong>Introduction: </strong>The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation.</p><p><strong>Methods: </strong>The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors.</p><p><strong>Results: </strong>A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (<i>P</i> < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (<i>P</i> < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (<i>P</i> = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (<i>P</i> = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (<i>P</i> = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (<i>P</i> < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (<i>P</i> < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis.</p><p><strong>Conclusion: </strong>For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/01/pbad008.PMC10249050.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9638034","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}
Monia Zidane, Marc Haber, Thérèse Truong, Frédérique Rachédi, Catherine Ory, Sylvie Chevillard, Hélène Blanché, Robert Olaso, Anne Boland, Éric Conte, Mojgan Karimi, Yan Ren, Constance Xhaard, Vincent Souchard, Jacques Gardon, Marc Taquet, André Bouville, Jean-François Deleuze, Vladimir Drozdovitch, Florent de Vathaire, Jean-Baptiste Cazier
Background: Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations.
Methods: We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population.
Results: We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10-7, 2.39 × 10-7, and 7.19 × 10-7 and corresponding odds ratios of 2.02, 1.89, and 2.37.
Conclusion: Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.
{"title":"Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.","authors":"Monia Zidane, Marc Haber, Thérèse Truong, Frédérique Rachédi, Catherine Ory, Sylvie Chevillard, Hélène Blanché, Robert Olaso, Anne Boland, Éric Conte, Mojgan Karimi, Yan Ren, Constance Xhaard, Vincent Souchard, Jacques Gardon, Marc Taquet, André Bouville, Jean-François Deleuze, Vladimir Drozdovitch, Florent de Vathaire, Jean-Baptiste Cazier","doi":"10.1093/pcmedi/pbad015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad015","url":null,"abstract":"<p><strong>Background: </strong>Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations.</p><p><strong>Methods: </strong>We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population.</p><p><strong>Results: </strong>We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10<sup>-7</sup>, 2.39 × 10<sup>-7,</sup> and 7.19 × 10<sup>-7</sup> and corresponding odds ratios of 2.02, 1.89, and 2.37.</p><p><strong>Conclusion: </strong>Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735912","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}
[This corrects the article DOI: 10.1093/pcmedi/pbad014.].
[更正文章DOI: 10.1093/pcmedi/pbad014.]。
{"title":"Correction to: New treatment for osteoarthritis: Gene therapy.","authors":"","doi":"10.1093/pcmedi/pbad016","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad016","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pcmedi/pbad014.].</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/ed/pbad016.PMC10294634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201091","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}
Pub Date : 2023-03-10eCollection Date: 2023-03-01DOI: 10.1093/pcmedi/pbad004
Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang
The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.
{"title":"Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.","authors":"Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang","doi":"10.1093/pcmedi/pbad004","DOIUrl":"10.1093/pcmedi/pbad004","url":null,"abstract":"<p><p>The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9595475","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}
Qing Zhang, Wen Wen Wu, Lei Li, Vanessa M McDonald, Yu Cheng Chen, Gang Wang, Peter G Gibson
Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β2-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.
{"title":"Workup of difficult-to-treat asthma: implications from treatable traits.","authors":"Qing Zhang, Wen Wen Wu, Lei Li, Vanessa M McDonald, Yu Cheng Chen, Gang Wang, Peter G Gibson","doi":"10.1093/pcmedi/pbad003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad003","url":null,"abstract":"<p><p>Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β<sub>2</sub>-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/91/pbad003.PMC10037422.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9274915","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}