Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100757
Kun-Ming Chan , Wei-Chen Lee
Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.
{"title":"Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis","authors":"Kun-Ming Chan , Wei-Chen Lee","doi":"10.1016/j.bj.2024.100757","DOIUrl":"10.1016/j.bj.2024.100757","url":null,"abstract":"<div><div>Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100757"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100766
Jong hoon Lee , Consolato Sergi , Richard E. Kast , Badar A. Kanwar , Jean Bourbeau , Sangsuk Oh , Mun-Gi Sohn , Chul Joong Lee , Michael D. Coleman
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus and govern induction, resulting in multiorgan impacts. Its pathophysiology involves the followings: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway: 3) the spike protein pathway. Therefore, it is necessary to block the pathological course with modulating innate lymphoid cells against diverse corona variants in the future.
{"title":"Basic implications on three pathways associated with SARS-CoV-2","authors":"Jong hoon Lee , Consolato Sergi , Richard E. Kast , Badar A. Kanwar , Jean Bourbeau , Sangsuk Oh , Mun-Gi Sohn , Chul Joong Lee , Michael D. Coleman","doi":"10.1016/j.bj.2024.100766","DOIUrl":"10.1016/j.bj.2024.100766","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus and govern induction, resulting in multiorgan impacts. Its pathophysiology involves the followings: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway: 3) the spike protein pathway. Therefore, it is necessary to block the pathological course with modulating innate lymphoid cells against diverse corona variants in the future.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100766"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100747
Hsin-Tzu Yeh , Sz-Wei Lu , Tzu-Heng Cheng , Jian-Xun Lu , Chien-Han Hsiao , Chieh-Ching Yen
Background
Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS.
Methods
We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) , and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria.
Results
Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38–76%) and 94% (95% CI, 89–97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85–94%) and 74% (95% CI, 61–84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92–0.96) vs. 0.87 (95% CI, 0.84–0.90)] in four studies.
Conclusions
Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.
{"title":"Diagnostic accuracy of transthoracic echocardiography for acute type A aortic syndrome: A systematic review and meta-analysis","authors":"Hsin-Tzu Yeh , Sz-Wei Lu , Tzu-Heng Cheng , Jian-Xun Lu , Chien-Han Hsiao , Chieh-Ching Yen","doi":"10.1016/j.bj.2024.100747","DOIUrl":"10.1016/j.bj.2024.100747","url":null,"abstract":"<div><h3>Background</h3><div>Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS.</div></div><div><h3>Methods</h3><div>We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) , and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria.</div></div><div><h3>Results</h3><div>Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38–76%) and 94% (95% CI, 89–97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85–94%) and 74% (95% CI, 61–84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92–0.96) vs. 0.87 (95% CI, 0.84–0.90)] in four studies.</div></div><div><h3>Conclusions</h3><div>Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100747"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100770
Ni-Chin Tsai , Chai-Wai Liou , Yin-Hua Cheng , Hao-Ting Lien , Tzu-Ling Lin , Tsu-Kung Lin , Min-Yu Lan , Pi-Lien Hung , Tzu-Jou Wang , Chen-Hao Lee , Yi-Chih Liang , Kuo-Chung Lan
Background
The aim of this study was to create a molecular diagnostic platform and establish a diagnostic pipeline for patients highly suspected of mitochondrial disorders. The effectiveness of three methods, namely, traditional restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR), Sanger sequencing for hotspot detection and whole mitochondrial DNA (mtDNA), and third-generation (Nanopore) whole mtDNA sequencing, will be compared in diagnosing patients with suspected primary mitochondrial diseases (PMDs). The strengths and limitations of different methods are also discussed.
Material and methods
A single-center prospective cohort study was conducted to validate the diagnostic pipeline for suspected mitochondrial diseases. In the first stage, a PCR-based method with five sets of primers was used to screen for eight hotspots (m.3243A > G, m.3460G > A, m.8344A > G, m.8993T > G, m.9185T > C, m.11778G > A, m.13513G > A, and m.4977deletion) using either RFLP or direct Sanger sequencing. Sanger sequencing was also used to confirm the RFLP-positive samples. In the second stage, for samples with negative screening results for the eight hotspots, mitochondrial whole-genome sequencing was performed using Sanger sequencing or third-generation nanopore sequencing.
Results
Between June 2020 and May 2023, 30 patients from ages 0 to 63 with clinically suspected mitochondrial disease were enrolled. The positive yield for the diagnosis of PMDs was 8/30 = 26.7%, and the sensitivity of the heteroplasmy level for the RFLP-based method was approximately 5%. The remaining 22 patients who tested negative at the first stage were tested using Sanger sequencing or the third-generation sequencing Nanopore, and all tested negative for pathological mtDNA mutations. Compared to the Sanger sequencing method, the results of RFLP-PCR were compromised by the limitations of incomplete RFLP enzyme digestion. For whole-genome sequencing of mtDNA, Sanger sequencing, instead of nanopore sequencing, is preferred at our institution because of its cost-effectiveness.
Conclusions
In our highly selective cohort, most tested positive in the first stage of the 8 hot spots screen. Sanger sequencing is a conventional and accurate method for mitochondrial disease screening, at least for the most common hot spots in the region. The results revealed that Sanger sequencing is an accurate method with the benefit of being more cost-effective. This integral platform of molecular diagnosis bears the advantages of being relatively low cost and having a shorter reporting time, facilitating crucial identification of patients with clinical evidence of such disorders. This diagnostic flowchart has also been translated into routine clinical use in the tertiary hospital.
{"title":"The establishment of a molecular diagnostic platform for mitochondrial diseases: From conventional to next-generation sequencing","authors":"Ni-Chin Tsai , Chai-Wai Liou , Yin-Hua Cheng , Hao-Ting Lien , Tzu-Ling Lin , Tsu-Kung Lin , Min-Yu Lan , Pi-Lien Hung , Tzu-Jou Wang , Chen-Hao Lee , Yi-Chih Liang , Kuo-Chung Lan","doi":"10.1016/j.bj.2024.100770","DOIUrl":"10.1016/j.bj.2024.100770","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to create a molecular diagnostic platform and establish a diagnostic pipeline for patients highly suspected of mitochondrial disorders. The effectiveness of three methods, namely, traditional restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR), Sanger sequencing for hotspot detection and whole mitochondrial DNA (mtDNA), and third-generation (Nanopore) whole mtDNA sequencing, will be compared in diagnosing patients with suspected primary mitochondrial diseases (PMDs). The strengths and limitations of different methods are also discussed.</div></div><div><h3>Material and methods</h3><div>A single-center prospective cohort study was conducted to validate the diagnostic pipeline for suspected mitochondrial diseases. In the first stage, a PCR-based method with five sets of primers was used to screen for eight hotspots (m.3243A > G, m.3460G > A, m.8344A > G, m.8993T > G, m.9185T > C, m.11778G > A, m.13513G > A, and m.4977deletion) using either RFLP or direct Sanger sequencing. Sanger sequencing was also used to confirm the RFLP-positive samples. In the second stage, for samples with negative screening results for the eight hotspots, mitochondrial whole-genome sequencing was performed using Sanger sequencing or third-generation nanopore sequencing.</div></div><div><h3>Results</h3><div>Between June 2020 and May 2023, 30 patients from ages 0 to 63 with clinically suspected mitochondrial disease were enrolled. The positive yield for the diagnosis of PMDs was 8/30 = 26.7%, and the sensitivity of the heteroplasmy level for the RFLP-based method was approximately 5%. The remaining 22 patients who tested negative at the first stage were tested using Sanger sequencing or the third-generation sequencing Nanopore, and all tested negative for pathological mtDNA mutations. Compared to the Sanger sequencing method, the results of RFLP-PCR were compromised by the limitations of incomplete RFLP enzyme digestion. For whole-genome sequencing of mtDNA, Sanger sequencing, instead of nanopore sequencing, is preferred at our institution because of its cost-effectiveness.</div></div><div><h3>Conclusions</h3><div>In our highly selective cohort, most tested positive in the first stage of the 8 hot spots screen. Sanger sequencing is a conventional and accurate method for mitochondrial disease screening, at least for the most common hot spots in the region. The results revealed that Sanger sequencing is an accurate method with the benefit of being more cost-effective. This integral platform of molecular diagnosis bears the advantages of being relatively low cost and having a shorter reporting time, facilitating crucial identification of patients with clinical evidence of such disorders. This diagnostic flowchart has also been translated into routine clinical use in the tertiary hospital.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100770"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2025.100852
Aila Akosua Kattner
This issue of the Biomedical Journal features a special section on epigenetics in infection, exploring epitranscriptomic modifications in the malaria parasite Plasmodium and the African sleeping sickness parasite Trypanosoma, with a focus on how these modifications influence parasite development and survival strategies. Additionally, this issue reviews regulatory mechanisms in asymmetric cell division, assessment needs for children with developmental coordination disorder along with recommendations, and advancements in 3D chondrocyte culturing for tissue engineering. Also examined are three key pathways exacerbating long COVID, the increasing impact of electromagnetic exposure in built environments on human health, and recent updates in liver transplantation criteria for hepatocellular carcinoma complicated by portal vein tumor thrombosis. Research in bladder cancer investigates the role of activating transcription factor 3, known for its anti-tumor properties, and its link to metformin. Another study demonstrates the efficacy of Sanger sequencing in streamlining mitochondrial disorder diagnostics, enabling timely identification based on clinical evidence. Additional studies present a novel intervention approach for autoimmune diseases, advancements in artificial bone grafts to enhance bone regeneration, and the benefits of public hospital participation in oncological clinical trials. Finally, a study confirms the suitability of transthoracic echocardiography for diagnosing suspected acute aortic syndrome.
{"title":"Sacred codes: Preservation, permutation and expression","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2025.100852","DOIUrl":"10.1016/j.bj.2025.100852","url":null,"abstract":"<div><div>This issue of the <em>Biomedical Journal</em> features a special section on epigenetics in infection, exploring epitranscriptomic modifications in the malaria parasite <em>Plasmodium</em> and the African sleeping sickness parasite <em>Trypanosoma</em>, with a focus on how these modifications influence parasite development and survival strategies. Additionally, this issue reviews regulatory mechanisms in asymmetric cell division, assessment needs for children with developmental coordination disorder along with recommendations, and advancements in 3D chondrocyte culturing for tissue engineering. Also examined are three key pathways exacerbating long COVID, the increasing impact of electromagnetic exposure in built environments on human health, and recent updates in liver transplantation criteria for hepatocellular carcinoma complicated by portal vein tumor thrombosis. Research in bladder cancer investigates the role of activating transcription factor 3, known for its anti-tumor properties, and its link to metformin. Another study demonstrates the efficacy of Sanger sequencing in streamlining mitochondrial disorder diagnostics, enabling timely identification based on clinical evidence. Additional studies present a novel intervention approach for autoimmune diseases, advancements in artificial bone grafts to enhance bone regeneration, and the benefits of public hospital participation in oncological clinical trials. Finally, a study confirms the suitability of transthoracic echocardiography for diagnosing suspected acute aortic syndrome.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100852"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes.
The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components.
Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair.
However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues.
Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.
{"title":"Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine","authors":"Yu-Ying Chu , Atsuhiko Hikita , Yukiyo Asawa , Kazuto Hoshi","doi":"10.1016/j.bj.2024.100786","DOIUrl":"10.1016/j.bj.2024.100786","url":null,"abstract":"<div><div>Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes.</div><div>The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components.</div><div>Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair.</div><div>However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues.</div><div>Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100786"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100774
Hsiao-Fan Chen , Kou-Juey Wu
Asymmetric cell division (ACD) plays a pivotal role in development, tissue homeostasis, and stem cell maintenance. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are key regulators of ACD, orchestrating the intricate molecular machinery that governs cell fate determination. This review summarizes current literature to elucidate the diverse roles of lncRNAs in modulating ACD across various biological contexts. The regulatory mechanisms of asymmetric cell division mediated by lncRNAs, including their interactions with protein effectors, epigenetic regulation, and subcellular localization are explored. Additionally, we discuss the implications of dysregulated lncRNAs in mediating ACD that lead to tumorigenesis. By integrating findings from diverse experimental models and cell types, this review provides insights into the multifaceted roles of lncRNAs in governing asymmetric cell division, shedding light on fundamental biological processes. Further research in this area may lead to the development of novel therapies targeting dysregulated lncRNAs to restore proper cell division and function. The knowledge of lncRNAs regulating ACD could potentially revolutionize the field of regenerative medicine and cancer therapy by targeting specific lncRNAs involved in ACD. By unraveling the complex interactions between lncRNAs and cellular processes, the potential novel opportunities for precision medicine approaches may be uncovered.
{"title":"LncRNAs and asymmetric cell division: The epigenetic mechanisms","authors":"Hsiao-Fan Chen , Kou-Juey Wu","doi":"10.1016/j.bj.2024.100774","DOIUrl":"10.1016/j.bj.2024.100774","url":null,"abstract":"<div><div>Asymmetric cell division (ACD) plays a pivotal role in development, tissue homeostasis, and stem cell maintenance. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are key regulators of ACD, orchestrating the intricate molecular machinery that governs cell fate determination. This review summarizes current literature to elucidate the diverse roles of lncRNAs in modulating ACD across various biological contexts. The regulatory mechanisms of asymmetric cell division mediated by lncRNAs, including their interactions with protein effectors, epigenetic regulation, and subcellular localization are explored. Additionally, we discuss the implications of dysregulated lncRNAs in mediating ACD that lead to tumorigenesis. By integrating findings from diverse experimental models and cell types, this review provides insights into the multifaceted roles of lncRNAs in governing asymmetric cell division, shedding light on fundamental biological processes. Further research in this area may lead to the development of novel therapies targeting dysregulated lncRNAs to restore proper cell division and function. The knowledge of lncRNAs regulating ACD could potentially revolutionize the field of regenerative medicine and cancer therapy by targeting specific lncRNAs involved in ACD. By unraveling the complex interactions between lncRNAs and cellular processes, the potential novel opportunities for precision medicine approaches may be uncovered.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100774"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100745
Benjamin Sian Teck Lee , Ameya Sinha , Peter Dedon , Peter Preiser
Ribonucleoside modifications comprising the epitranscriptome are present in all organisms and all forms of RNA, including mRNA, rRNA and tRNA, the three major RNA components of the translational machinery. Of these, tRNA is the most heavily modified and the tRNA epitranscriptome has the greatest diversity of modifications. In addition to their roles in tRNA biogenesis, quality control, structure, cleavage, and codon recognition, tRNA modifications have been shown to regulate gene expression post-transcriptionally in prokaryotes and eukaryotes, including humans. However, studies investigating the impact of tRNA modifications on gene expression in the malaria parasite Plasmodium falciparum are currently scarce. Current evidence shows that the parasite has a limited capacity for transcriptional control, which points to a heavier reliance on strategies for posttranscriptional regulation, such as tRNA epitranscriptome reprogramming. This review addresses the known functions of tRNA modifications in the biology of P. falciparum while highlighting the potential therapeutic opportunities and the value of using P. falciparum as a model organism for addressing several open questions related to the tRNA epitranscriptome.
{"title":"Charting new territory: The Plasmodium falciparum tRNA modification landscape","authors":"Benjamin Sian Teck Lee , Ameya Sinha , Peter Dedon , Peter Preiser","doi":"10.1016/j.bj.2024.100745","DOIUrl":"10.1016/j.bj.2024.100745","url":null,"abstract":"<div><div>Ribonucleoside modifications comprising the epitranscriptome are present in all organisms and all forms of RNA, including mRNA, rRNA and tRNA, the three major RNA components of the translational machinery. Of these, tRNA is the most heavily modified and the tRNA epitranscriptome has the greatest diversity of modifications. In addition to their roles in tRNA biogenesis, quality control, structure, cleavage, and codon recognition, tRNA modifications have been shown to regulate gene expression post-transcriptionally in prokaryotes and eukaryotes, including humans. However, studies investigating the impact of tRNA modifications on gene expression in the malaria parasite <em>Plasmodium falciparum</em> are currently scarce. Current evidence shows that the parasite has a limited capacity for transcriptional control, which points to a heavier reliance on strategies for posttranscriptional regulation, such as tRNA epitranscriptome reprogramming. This review addresses the known functions of tRNA modifications in the biology of <em>P. falciparum</em> while highlighting the potential therapeutic opportunities and the value of using <em>P. falciparum</em> as a model organism for addressing several open questions related to the tRNA epitranscriptome.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 2","pages":"Article 100745"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100703
Gayathri Govindaraju , Arumugam Rajavelu
Epigenetic machinery has emerged as a central player in gene regulation and chromatin organization in Plasmodium spp. Epigenetic modifications on histones and their role in antigenic variation in P. falciparum are widely studied. Recent discoveries on nucleic acid methylome are exciting and provide a new dimension to the apicomplexan protozoan parasite's gene regulatory process. Reports have confirmed that N6-methyl adenosine (m6A) methylation plays a crucial role in the translational plasticity of the human malaria parasite during its development in RBC. The YTH domain (YT521-B Homology) protein in P. falciparum binds to m6A epitranscriptome modifications on the mRNA and regulates protein translation. The binding of the PfYTH domain protein to the m6A-modified mRNA is mediated through a binding pocket formed by aromatic amino acids. The P. falciparum genome encodes two members of YTH domain proteins, i.e., YTH1 and YTH2, and both have distinct roles in dictating the epitranscriptome in human malaria parasites. This review highlights recent advancements in the functions and mechanisms of YTH domain protein's role in translational plasticity in the various developmental stages of the parasite.
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Pub Date : 2025-04-01DOI: 10.1016/j.bj.2024.100750
Yuan-Hsin Tsai , Chun-Chieh Tseng , Yun-Chan Lin , Howida M. Nail , Kuan-Yu Chiu , Yen-Hao Chang , Ming-Wei Chang , Feng-Huei Lin , Hui-Min David Wang
Background
Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM).
Methods
This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well.
Results
The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis.
Conclusion
In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.
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