Translational medicine communications最新文献

{"title":"Organizational aspects of tissue engineering clinical translation: insights from a qualitative case study.","authors":"Renan Gonçalves Leonel da Silva, Larry Au, Alessandro Blasimme","doi":"10.1186/s41231-024-00179-7","DOIUrl":"10.1186/s41231-024-00179-7","url":null,"abstract":"<p><strong>Background: </strong>Tissue engineering is a multidisciplinary field that combines principles from cell biology, bioengineering, material sciences, medicine and surgery to create functional and viable bioproducts that can be used to repair or replace damaged or diseased tissues in the human body. The complexity of tissue engineering can affect the prospects of efficiently translating scientific discoveries in the field into scalable clinical approaches that could benefit patients. Organizational challenges may play a key role in the clinical translation of tissue engineering for the benefit of patients.</p><p><strong>Methods: </strong>To gain insight into the organizational aspects of tissue engineering that may create impediments to efficient clinical translation, we conducted a retrospective qualitative case study of one tissue engineering multi-site translational project on knee cartilage engineered tissue grafts. We collected qualitative data using a set of different methods: semi-structured interviews, documentary research and audio-visual content analysis.</p><p><strong>Results: </strong>Our study identified various challenges associated to first-in-human trials in tissue engineering particularly related to: logistics and communication; research participant recruitment; clinician and medical student participation; study management; and regulation.</p><p><strong>Conclusions: </strong>While not directly generalizable to other types of advanced therapies or to regenerative medicine in general, our results offer valuable insights into organizational barriers that may prevent efficient clinical translation in the field of tissue engineering.</p>","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"9 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer.","authors":"Karen Schmidt, Amber Thatcher, Albert Grobe, Pamela Broussard, Linda Hicks, Haiwei Gu, Lesley G Ellies, Dorothy D Sears, Leonid Kalachev, Eugene Kroll","doi":"10.1186/s41231-024-00178-8","DOIUrl":"10.1186/s41231-024-00178-8","url":null,"abstract":"<p><strong>Background: </strong>Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabolic shift in response to hypoxic conditions.</p><p><strong>Methods: </strong>To leverage the glucose dependency of hypoxic tumor cells, we assessed the effects of a mild reduction in systemic glucose by controlling both dietary carbohydrates with a ketogenic diet and endogenous glucose production by using metformin on two mouse models of triple-negative breast cancer (TNBC).</p><p><strong>Results: </strong>Here, we showed that animals with TNBC treated with the combination regimen of ketogenic diet and metformin (a) had their tumor burden lowered by two-thirds, (b) displayed 38% slower tumor growth, and (c) showed 36% longer latency, compared to the animals treated with a ketogenic diet or metformin alone. As a result, lowering systemic glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse TNBC models by 31 days, approximately equivalent to 3 years of life extension in human terms.</p><p><strong>Conclusion: </strong>This preclinical study demonstrates that reducing systemic glucose by combining a ketogenic diet and metformin significantly inhibits tumor proliferation and increases overall survival. Our findings suggest a possible treatment for a broad range of hypoxic and glycolytic tumor types that can augment existing treatment options to improve patient outcomes.</p>","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of derinat as a treatment for murine and androgenetic alopecia (AGA) patients","authors":"Ching-Ying Wu, Wei-Chiao Chen, Cheng-Hsu Hsieh, Yun-Fang Liang, Wei-Ju Li, Hao Shen, Wei-Yen Wei, Ting-Yu Chou, Yen-Chun Chiu, Hao Huang, Wen-Li Hsu","doi":"10.1186/s41231-023-00159-3","DOIUrl":"https://doi.org/10.1186/s41231-023-00159-3","url":null,"abstract":"Abstract Background Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca 2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis. Methods The lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects. Results Derinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life. Conclusions Derinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022. Trial registration ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"103 16","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135138172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the clinical and genetical spectrum of ADPKD in Chile to assess ProPKD score as a risk prediction tool","authors":"Esperanza Bayyad, Anita Plaza, Jaime Klenner, Patricio Downey, Paulina Salas, Daniela Maragaño, Patricio Herrera, Paula Lehmann, Lily Quiroz, María Jesus Zavala, Karen Orostica, Claudio Flores, Leopoldo Ardiles, Jorge Maturana, Paola Krall","doi":"10.1186/s41231-023-00157-5","DOIUrl":"https://doi.org/10.1186/s41231-023-00157-5","url":null,"abstract":"Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score. Methods We enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data. Results ADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001). Conclusion This study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135113938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of lipopolysaccharide-induced otic injury by a single dose administration of a novel dexamethasone formulation","authors":"Silvia Murillo-Cuesta, Ester Lara, Jose M. Bermúdez-Muñoz, Elena Torres-Campos, Lourdes Rodríguez-de la Rosa, Pilar López-Larrubia, Signe R. Erickson, Isabel Varela-Nieto","doi":"10.1186/s41231-023-00156-6","DOIUrl":"https://doi.org/10.1186/s41231-023-00156-6","url":null,"abstract":"Abstract Background The blood-labyrinth barrier (BLB) separates the inner ear from the circulation and is critical for maintaining ionic homeostasis and limiting the entry of deleterious agents. BLB integrity is disrupted by bacterial lipopolysaccharide (LPS), which elicits a strong inflammatory response in the inner ear leading to irreversible otic damage. Prolonged administration of systemic corticosteroids is the available treatment, but it shows both limited efficacy and major adverse effects. SPT-2101 is a novel in situ-forming gel formulation of dexamethasone allowing slow and sustained drug release after single intratympanic administration. Methods We used a rat model of LPS-induced injury to define the functional, cellular and molecular mechanisms associated to BLB dysfunction and the protection by SPT-2101. Hearing was assessed by auditory brainstem response (ABR) recording, BLB permeability by gadolinium dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and Evans blue extravasation. Gross cochlear histology and cellular alterations were studied by hematoxylin-eosin staining and immunofluorescence. RT-qPCR, PCR array and western blotting were used to assess transcriptional and protein changes. Results LPS-challenged rats showed BLB breakdown and altered permeability as shown by the progressive increase in cochlear gadolinium uptake and Evans blue incorporation. LPS administration increased the cochlear expression of the LPS toll-like receptors Tlr2 and co-receptor Cd14 , pro-inflammatory cytokines and receptors such as Il1b and ll1r1 , and also the oxidative stress and inflammasome mediators NRF2 and NLRP3. LPS also increased IBA1-positive macrophage infiltration in the lateral wall and spiral ganglion. A single intratympanic injection of SPT-2101 protected BLB integrity and prevented otic injury. Comparable effects were obtained by repeated administration of systemic dexamethasone, but not by a single dose. SPT-2101 administration normalized molecular inflammatory mediators and suppressed macrophage infiltration. Conclusions Our data indicate that single local administration of dexamethasone formulated as SPT-2101 protects BLB functional integrity during endotoxemia, providing a novel therapeutic opportunity to treat diseases related to BLB dysfunction.","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"109 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136063046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial peptide Mastoparan X has good activity against Escherichia coli in vitro and alleviates its pathogenicity in mice","authors":"Xueqin Zhao, Weiyu Luo, Lei Wang, Chunling Zhu, Xianghong Xue, Xiaojing Xia, Xilong Wu, Yueyu Bai, Jianhe Hu","doi":"10.1186/s41231-023-00145-9","DOIUrl":"https://doi.org/10.1186/s41231-023-00145-9","url":null,"abstract":"Abstract Background Escherichia coli is a facultative anaerobic bacterium that normally resides in the gastrointestinal tract of humans and animals but can cause diarrhea and enteritis. MPX is an antimicrobial peptide extracted from wasp venom and has potent bactericidal effects against many bacteria. This study aimed to investigate the mechanism of MPX’s bactericidal activity against E. coli in vitro, its effect on IPEC-J2 cell apoptosis and barrier function, and its therapeutic efficacy against E. coli infection in mice. Methods The effects of MPX on E. coli were investigated in vitro, at the cellular level, and in vivo. Results The study found that the MIC of MPX against E. coli was 31.25 µg/mL, and scanning electron microscopy showed that MPX caused the bacteria to become smaller in size with leaked contents. Additionally, NPN, PI, and DiSC3(5) results showed that MPX positively correlated with the fluorescence intensity. MPX significantly inhibited E. coli biofilm formation. Furthermore, MPX effectively reduced IPEC-J2 cell apoptosis, regulated ZO-1, Occludin, and Claudin-1 expression through the Rac1 pathway, and alleviated the pathological damage in the intestine, as shown by H&amp;E staining results. qRT-PCR results indicated that MPX increased TFF3 mRNA expression in the jejunum and colon. Conclusions This study is the first to explore the mechanism of MPX's bactericidal activity against E. coli in vitro, providing a foundation for developing new drugs to treat bacterial infections. Graphical Abstract","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"304 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135830063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of clonal hematopoiesis in COVID-19 patients at high risk for adverse clinical outcomes","authors":"Cathy Smith, Bala B. Burugula, Morgan A. Jones, Qing Li, Jacob O. Kitzman, Terrence N. Wong","doi":"10.1186/s41231-023-00155-7","DOIUrl":"https://doi.org/10.1186/s41231-023-00155-7","url":null,"abstract":"Abstract Purpose Clonal hematopoiesis (CH) describes the aging-associated expansion of mutant hematopoietic cell populations. In various cohorts, CH has been associated with increased morbidity and mortality from non-hematologic diseases such as cardiovascular disease and infections, including COVID-19. Comorbidities placing individuals at risk of complications from these disorders, such as diabetes, also increase in prevalence with age and frequently co-exist with CH. How CH interacts with other aging-associated comorbidities to impact human health remains unknown. Methods We assessed the impact of CH on the pre-existing end-organ damage and ultimate clinical outcomes among 242 patients hospitalized with COVID-19 at Michigan Medicine from March to June of 2020. In contrast to most previous studies, these patients skewed older with the majority having multiple comorbidities, which placed them at higher risk for end-organ damage and poor clinical outcomes. Results Overall CH was not significantly associated with increased COVID-19 mortality after controlling for other risk factors, although we did note a borderline-significant association specifically for non- DNMT3A CH mutations. In contrast, we observed a significant association between CH and pre-existing chronic kidney disease (CKD), which was strongest for DNMT3A mutant CH. Conclusions These data suggest that the clinical impact of CH is influenced by the specific gene(s) mutated and is further modified by other comorbidities and clinical risk factors frequently present in the elderly.","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135369265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the complexity: understanding the deconvolutions of RNA-seq data","authors":"Kavoos Momeni, Saeid Ghorbian, Ehsan Ahmadpour, Rasoul Sharifi","doi":"10.1186/s41231-023-00154-8","DOIUrl":"https://doi.org/10.1186/s41231-023-00154-8","url":null,"abstract":"Abstract Deconvolution of RNA sequencing data is a computational method used to estimate the relative proportions of different cell types or subpopulations within a heterogeneous sample based on gene expression profiles. This technique is particularly useful in studies where the goal is to identify changes in gene expression that are specific to a particular cell type or subpopulation. The deconvolution process involves using reference gene expression profiles from known cell types or subpopulations to infer the relative abundance of these cells within a mixed sample. This is typically done using linear regression or other statistical methods to model the observed gene expression data as a linear combination of the reference profiles. Once the relative proportions of each cell type or subpopulation have been estimated, downstream analyses can be performed on each component separately, allowing for more precise identification of cell-type-specific changes in gene expression. Overall, deconvolution of RNA sequencing data is a powerful tool for dissecting complex biological systems and identifying cell-type-specific molecular signatures that may be relevant for disease diagnosis and treatment.","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134959985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational research and key aspects to make it successful","authors":"Animesh Acharjee","doi":"10.1186/s41231-023-00153-9","DOIUrl":"https://doi.org/10.1186/s41231-023-00153-9","url":null,"abstract":"","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135155112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the knowledge structure of a gluten-free diet: a global perspective","authors":"Sa ’ed H. Zyoud, Muna Shakhshir, Amani S. Abushanab, Amer Koni, Moath Hamdallah, Samah W. Al-Jabi","doi":"10.1186/s41231-023-00152-w","DOIUrl":"https://doi.org/10.1186/s41231-023-00152-w","url":null,"abstract":"","PeriodicalId":75244,"journal":{"name":"Translational medicine communications","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45281107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}