MOTS-c

For Rapid Identification of Patients Susceptible to Antibiotic-Induced Hearing LossMISSISSAUGA, Ontario and MANCHESTER, United Kingdom, Dec. 10, 2024 (GLOBE NEWSWIRE) -- Microbix Biosystems Inc. (TSX: MBX, OTCQX: MBXBF, Microbix®), a life sciences innovator, manufacturer, and exporter, and EMQN CIC (EMQN), a global supplier of laboratory external quality assessment (“EQA”) schemes for human genomic testing, announce the go-live of a program to support the accurate identification of patients who carry a gene-variant associated with increased susceptibility to hearing loss following treatment with a widely-used class of antibiotics. This first-of-its kind EQA program is intended to help ensure the proficiency of Point-of-Care Testing (“POCT”) and acute-care labs that are assessing whether patients carry the MT-RNR1 m.1555A>G gene variant. It is estimated that one in 500 persons carry this variant that can lead to profound and irreversible hearing loss upon exposure to aminoglycoside antibiotics. This class of antibiotics include Gentamycin, Kanamycin, Streptomycin, and Tobramycin, which are used to treat a wide range of “gram negative” bacterial infections. Of particular concern are newborn babies who are suspected to be at risk of bacterial sepsis – a life-threatening condition that can lead to death from multi-organ failure if not treated promptly with appropriate antibiotic drugs and other acute medical care. Microbix-produced quality assessment products (“QAPs™”), formatted onto Copan® FLOQSwabs®, are being used in this EMQN EQA program to help assess the proficiency and accuracy of such acute care genetic testing. The QAPs provide samples that participants can process like cheek or buccal swabs, enabling them to verify the accuracy of MT-RNR1 assays in their POCT. With a subscription to this EMQN program, participants will receive three samples every two months (18 per year), helping them to ensure the accuracy of their testing on an ongoing basis and thereby make the most reliable diagnoses possible. Sean Sales, Operations Director at EMQN, commented, “It has been a pleasure to have Microbix’s assistance in making the QAPs for this groundbreaking and important new EQA program. Acute care physicians need the information to be able to evaluate the risk-benefit of antibiotic treatments and no patient should have to face a lifetime of hearing loss when tests to identify this risk are available.” Cameron Groome, CEO and President at Microbix also commented, “We’re pleased to help enable the creation of EQA for this clinically-important decision-making. Our expertise was joined to that of EMQN and Copan to ensure that accurate testing and properly-directed treatment is available for patients worldwide. This QAP marks Microbix’s entry into supporting the accuracy of genetic tests, adding to our established presence in infectious diseases and emerging role in oncology.” UK and international labs can enroll in this EQA program (code POCT MT-RNR1 25) via EMQN CIC at https://www.emqn.org/our-eqa-schemes/ and enquiries about Microbix QAPs can be directed to customer.service@microbix.com. About EMQN CICEMQN is a Manchester, UK based company that provides quality assurance tools and specialized knowledge to the human genomic testing community through External Quality Assessment (EQA) schemes. Its work helps guarantee the best possible molecular diagnostic procedure, analytical performance, and clinical interpretation. EMQN’s highly qualified peer group of assessors take pride in their thought leadership position and are committed to regularly publishing best practice guidelines and other information for the molecular diagnostics field. EMQN is accredited by the United Kingdom Accreditation Service (UKAS) to the international standard for EQA scheme providers, ISO 17043. About Microbix Biosystems Inc.Microbix Biosystems Inc. creates proprietary biological products for human health, with over 100 skilled employees and sales now targeting C$ 2.0 million or more per month. It makes and exports a wide range of critical ingredients and devices for the global diagnostics industry, notably antigens for immunoassays and its laboratory quality assessment products (QAPs™) that support clinical lab proficiency testing, enable assay development and validation, or help ensure the quality of clinical diagnostic workflows. Its antigens drive the antibody tests of approximately 100 diagnostics makers, while QAPs are sold to clinical lab accreditation organizations, diagnostics companies, and clinical labs. Microbix QAPs are now available in over 30 countries, supported by a network of international distributors. Microbix is ISO 9001 & 13485 accredited, U.S. FDA registered, Australian TGA registered, Health Canada establishment licensed, and provides IVDR compliant CE marked products across the EU. Forward-Looking InformationThis news release includes “forward-looking information,” as such term is defined in applicable securities laws. Forward-looking information includes, without limitation, discussion of the tests, the EQA program, EMQN, Copan, or their relevance, Microbix’s products or services, business and business results, goals or outlook, risks associated with financial results and stability, development projects such as those referenced in its presentations, regulatory compliance and approvals, sales to foreign jurisdictions, engineering and construction, production (including control over costs, quality, quantity or timeliness of delivery), currency exchange rates, maintaining adequate working capital or raising new capital on acceptable terms or at all, and other similar statements about anticipated future events, conditions or results that are not historical facts. These statements reflect management’s current estimates, beliefs, intentions, and expectations; they are not guarantees of future performance. Microbix cautions that all forward-looking information is inherently uncertain, and actual performance may be affected by a number of material factors, some of which are beyond its control. Accordingly, actual future events, conditions and results may differ materially from the estimates, beliefs, intentions, and expectations expressed or implied in the forward-looking information. All statements are made as of the date of this news release and represent Microbix’s judgement as of the date of this new release, and it is under no obligation to update or alter any forward-looking information. Please visit https://microbix.com or www.sedar.com for recent Microbix news and filings. For further information, please contact Microbix at: Cameron Groome, CEO(905) 361-8910Jim Currie, CFO(905) 361-8910Deborah Honig, Investor RelationsAdelaide Capital Markets(647) 203-8793 ir@microbix.com Copyright © 2024 Microbix Biosystems Inc. Microbix®, DxTM™, Kinlytic®, and QAPs™ are trademarks of Microbix Biosystems Inc.Copan®, FLOQ®, and FLOQSwab® are trademarks of Copan Italia S.p.A.

【导读】 线粒体-细胞核通讯在维持细胞稳态中起着至关重要的作用。MOTS-c是一种来源于线粒体DNA 12S rRNA的短肽，已被认为是一种逆行线粒体信号。虽然最近的临床研究表明MOTS-c与人类肿瘤之间可能存在联系，但MOTS-c在肿瘤发生中的作用仍有待研究。 9月25日，李积彬教授研究团队在期刊《Advanced Science》上发表了题为“Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination”的研究论文，本研究中，研究人员发现MOTS-c水平在卵巢癌患者的血清和肿瘤组织中均降低，与患者的不良预后相关。外源性MOTS-c抑制OC细胞的增殖、迁移和侵袭，并诱导细胞周期阻滞和凋亡。机制上，MOTS-c与LARS1相互作用并促进其泛素化和蛋白酶体降解。此外，USP7是LARS1的去泛素化酶，MOTS-c可通过与USP7竞争与LARS1结合来减弱USP7介导的LARS1去泛素化。另外，研究人员发现LARS1在卵巢癌中表达升高，并发挥重要的致癌功能。更重要的是，MOTS-c对OC具有明显的抗肿瘤作用，且无全身毒性。 综上所述，本研究揭示了MOTS-c在卵巢癌中的重要作用，为MOTS-c作为卵巢癌治疗靶点提供了可能。 https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/advs.202405620 背景知识 01 卵巢癌(OC)是最致命的妇科恶性肿瘤，2020年全球新诊断31.4万例，同年死亡20.7万例。尽管OC患者通过手术和化疗获得了暂时的临床缓解，但可用的治疗方案仍然有限，尤其是那些面临肿瘤复发和化疗药物耐药的患者。因此，在过去的30年里，OC患者的总生存率没有显示出实质性的提高。仅30.8%的晚期OC患者能生存5年。因此，迫切需要寻找新的抗肿瘤靶点及其治疗药物来延长OC患者的生存期。 线粒体是生物能和生物合成细胞器。癌细胞通过重编程线粒体代谢来维持其增殖，从而为脂质、核酸和蛋白质合成提供原料。此外，线粒体也是细胞内通讯和信号转导的重要枢纽。在代谢应激下，线粒体通过产生多种逆行信号改变核基因表达，帮助细胞适应受损的稳态。线粒体-细胞核通讯的参与在肿瘤细胞中经常观察到。因此，靶向这些线粒体逆行信号(线粒体ROS、肿瘤代谢物、线粒体钙等)是目前很有前景的抗癌策略。 MOTS-c是一种由线粒体12S rRNA编码的线粒体来源的16个氨基酸组成的多肽，近年来被认为是参与线粒体逆行信号调节的关键因子。在代谢应激时，MOTS-c转位至细胞核并与转录因子NRF2结合，参与调控核基因表达，维持细胞稳态。最近有报道称，MOTS-c在乙型肝炎病毒相关肝细胞癌患者中减少，外源性MOTS-c通过促进线粒体融合抑制乙型肝炎病毒DNA复制，从而保护肝功能。此外，肺癌患者放疗后MOTS-c水平显著升高。另外，MOTS-c与患前列腺癌和乳腺癌的可能性相关，且存在种族差异。所有这些研究均提示MOTS-c与肿瘤发生可能存在关联。然而，MOTS-c在包括OC在内的人类肿瘤中的生物学功能仍未被探索。 LARS1是OC的促癌因子 02 虽然LARS1在其他肿瘤中已被证明是一种促进癌症发展的分子，但在OC中的作用尚不明确。为了阐明LARS1在OC中的功能，研究人员构建了LARS1 shRNA质粒并降低了OC细胞中LARS1的表达。LARS1沉默显著降低了OC细胞的增殖能力，如CCK8和克隆形成试验所示。同时，LARS1水平的降低也导致OC细胞的迁移和侵袭能力明显低于阴性对照组。总之，这些发现表明LARS1是OC中的一种促进癌症发展的因子。然而，LARS1如何影响OC细胞的生长仍不清楚。LARS1作为已知的mTORC1激活剂，前期数据也证实MOTS-c可以降低OC细胞中LARS1蛋白水平并抑制mTORC1信号通路，这表明LARS1可能通过mTORC1信号通路影响OC细胞的生长。为了证实这一点，研究人员在OC细胞SKOV3中过表达LARS1，并用雷帕霉素（RAPA，一种mTORC1抑制剂）对其进行处理。结果显示，RAPA显著逆转了LARS1过表达引起的细胞增殖、迁移和侵袭能力增强。上述结果表明，LARS1通过调节mTORC1信号通路影响OC的肿瘤进展。 过表达LARS1逆转MOTS-c介导的卵巢癌肿瘤抑制作用 03 为了进一步确定LARS1通过MOTS-c治疗而下调与OC细胞增殖、迁移和侵袭之间的关系，研究人员建立了A2780和SKOV3细胞的稳定过表达LARS1模型。CCK8和克隆形成实验表明，LARS1的过表达显著增强了A2780和SKOV3细胞的增殖，并减轻或部分逆转了MOTS-c治疗引起的增殖抑制。同样，伤口愈合和迁移实验的结果表明，LARS1水平的升高显著增强了OC细胞的迁移和侵袭能力，从而抵消了MOTS-c的作用。这些发现表明，MOTS-c通过靶向LARS1来抑制OC的进展。 MOTS-c在体内显示出显著的抗肿瘤作用，能够抑制OC的生长，同时没有明显的系统毒性 04 为了评价MOTS-c在体内的抗肿瘤效果，研究人员利用A2780细胞构建了雌性裸鼠异种移植模型。结果显示，MOTS-c治疗显著抑制了OC细胞的生长，减少了肿瘤体积和重量。免疫组化分析显示，MOTS-c治疗抑制了肿瘤细胞的增殖，Ki67阳性细胞比例显著低于对照组。同时，MOTS-c治疗后LARS1的表达显著降低。此外，为了评估MOTS-c在体内是否有毒性，研究人员对两组小鼠的心脏、肝脏和肾脏进行了H&E染色，并从两组小鼠中收集了血清样本进行生化检测。在组织病理切片和生化检测结果的分析中未发现明显的毒性。综上所述，上述结果表明MOTS-c在体内可抑制OC细胞的生长且无毒性。 MOTS-c在体内显示出显著的抗肿瘤作用，对OC生长无系统毒性 研究小结 05 总之，研究人员已经证实MOTS-c在OC中的表达减少，并且低水平的MOTS-c表达与不良预后相关。体外和体内实验表明，外源性MOTS-c可以抑制OC细胞的生长。机制上，MOTS-c通过抑制USP7介导的LARS1去泛素化作用并促进LARS1降解来发挥抗癌作用。本研究首次揭示MOTS-c作为一种抗肿瘤肽可以抑制OC进展，因此它可能是未来OC诊断和治疗的一个潜在靶点。 【参考资料】 https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/advs.202405620 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 热门推荐活动 点击免费报名 🕓 上海｜11月15日-16日 ▶ 2024第一届中国类器官转化医学大会 点击对应文字 查看详情

MADERA, Calif., June 25, 2024 /PRNewswire/ -- What if a gentle swab of an infant's cheek was all it took to know if giving them a common antibiotic could also lead to long-term hearing loss? Continue Reading Dr. Jeremy Woods, Valley Children's Precision Medicine Director, with machine that tests for changes in the MT-RNR1 gene Valley Children's Hospital, located in Madera, California (PRNewsfoto/Valley Children's Healthcare) That is what Valley Children's Precision Medicine Program is doing: the team is the first in the nation to use a revolutionary genetic test that can quickly let a doctor know if their tiny patient is at higher risk of hearing damage from a type of antibiotic known as an aminoglycoside. Once a doctor knows that the baby has a particular version of a key hearing gene, they can then choose a different course of care to treat an infection. "Genes are like the individual instructions in a book that tell the body how to build and work, so understanding them is important in creating a treatment plan for each patient," said Dr. Jeremy Woods, Valley Children's geneticist and director of the Precision Medicine Program. Aminoglycosides are a class of antibiotics often used to treat infections for infants in the neonatal intensive care unit (NICU). But in addition to attacking bacteria, the medicines can also attack human proteins that are vital to hearing development. That's not usually a problem, but for babies born with certain variants of the MT-RNR1 gene, the risk for aminoglycoside-induced hearing loss (AIHL) is much greater. Insights suggest that this could be the explanation for at least 1% of hearing loss that occurs in children before language development, and likely more. The problem until now was being able to check the baby's genetic "map" quickly if they got sick. Valley Children's has solved that with a simple, non-invasive test. A small saliva sample from the baby's cheek is then analyzed by a special machine that tests for changes in the MT-RNR1 gene. The machine is no larger than an inkjet printer and can deliver results to physicians in under an hour when time is of the essence. Valley Children's Precision Medicine team is conducting MT-RNR1 rapid testing for patients outside of the hospital, with plans to standardize this process for babies in the hospital later this year. "Previously, we would have to wait weeks for the results of MT-RNR1 genetic testing. Now, we can have results back in under an hour," Dr. Woods said. "That gives us plenty of time to choose a safer antibiotic to treat a seriously ill baby." This life-changing advancement is one of several innovative tools pioneered by Valley Children's Precision Medicine Program. Earlier this year, the hospital began using an advanced genetic testing module as part of the electronic patient information system. This system allows providers to effortlessly order a comprehensive genetic test (whole genome sequencing) that includes one or both parents and provides instant care recommendations based on a child's specific genetic map. Valley Children's was also one of only five institutions to participate in a Medi-Cal pilot program called Project Baby Bear, which used rapid whole genome sequencing to improve the care for critically ill infants with undiagnosed illnesses. "Standardizing genome testing in the NICU underscores our commitment to utilizing cutting-edge technology and genetics to provide our patients with more than the best care, but the specialized kind of care they need," Dr. Woods said. About Valley Children's Healthcare Valley Children's Healthcare provides Central California's only high-quality, comprehensive care exclusively for children, from before birth to young adulthood. Our network offers highly specialized medical and surgical services to care for children with conditions ranging from common to the highly complex at its 358-bed stand-alone children's hospital that includes 28 NICU beds at partner hospitals. In addition, the Valley Children's Healthcare network includes specialty care centers, pediatric primary care practices and women's health services. Our family-centered, pediatric services extend from a leading pediatric cancer and blood diseases center on the West Coast, and a pediatric heart center known for its expertise and pioneering treatments, to an 88-bed Regional Level IV neonatal intensive care unit (NICU), the highest-level referral center between Los Angeles and the Bay Area. Valley Children's was the first children's hospital west of the Rockies to receive Magnet Nursing designation, the highest nursing benchmark in the world. In 2023, U.S. News and World Report again named Valley Children's one of the best children's hospitals in the country in seven pediatric specialties. With more than 670 physicians and 3,500 staff, Valley Children's delivers high-quality, comprehensive care to more than 1.3 million children from Kern County to the state capital and from the Central Coast to the Sierra. For more information, please visit SOURCE Valley Children's Healthcare