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Researchers investigate the intricacies of various cellular processes and pathologies and identify compounds with untapped therapeutic potential XI'AN, China, March 29, 2024 /PRNewswire/ -- Understanding the underlying mechanisms of normal and pathological cellular processes is essential for developing new drugs. Fortunately, modern techniques and experimental methods have greatly accelerated progress. The latest issue of JPA features three articles in which candidate compounds for treating complex disorders were successfully identified, alongside their detailed mechanisms of action. Continue Reading Recent JPA studies identify, through detailed analyses of molecular mechanisms and cellular processes, three potential drug candidates for three different pathologies. The first study investigated the use of metformin (Met), a drug used to manage type II diabetes, for treating benign prostate hyperplasia (BPH). The article was published in Volume 14, Issue 1 of the journal in January 2024. The researchers first sought to shed light on how and which dysregulated sex steroid hormone-related pathways shape the pathological characteristics of BPH, and whether Met can restore these pathways. Through retrospective analysis of data from BPH patients and clinical assessment of serum and tissue samples, the researchers identified dihydrotestosterone (DHT) as a major contributor to BPH among dysregulated sex hormones. DHT promotes prostate cell proliferation by upregulating androgen receptors and forming YAP1-TEAD4 heterodimers. In vivo experiments showed that Met treatment restored sex hormone homeostasis and inhibited DHT-induced cell proliferation. "Our study provided strong evidence that Met might be a promising clinical therapeutic approach for the treatment of BPH," remark corresponding authors Prof. Qian Lu and Prof. Xiaoxing Yin. In the second study, scientists explored the role of epimedin B (EB), the main flavonoid in the Chinese herb Epimedium brevicornum Maxim., in melanogenesis. They expanded on previous findings showing EB's ability to induce melanogenesis and activate tyrosinase family of proteins (TYRs). Through comprehensive in vitro and in vivo experiments on human and animal cells, they uncovered how EB modulated TYRs, increased melanosome numbers, promoted maturation, and aided depigmentation and repigmentation. "Our data reveals that EB can stimulate the pigmentation function of TYRs, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries," comments corresponding authors Dr. Yiming Li and Prof. Huali Wu. Finally, in the third study, researchers investigated ferroptosis, a type of programmed cell death, and its role in nerve regeneration after peripheral nerve injury (PNI). They found that oxidative stress at the injury site not only triggered both apoptosis and ferroptosis in nearby neurons by increasing intracellular iron via the degradation of ferroportin by UBA52. Using the Drug Signatures Database, they identified hydralazine (HYD), a potent arterial vasodilator, as a potential UBA52 disruptor. Early HYD administration after PNI in vivo expedited axon regeneration and motor function recovery, partly by suppressing ferroptosis. "The potential clinical implementation of HYD may lead to a reduction in the prevalence of individuals with mild symptoms of nerve damage, consequently mitigating the societal burden," conclude corresponding authors Dr. Bing Xia, Prof. Zhuojing Luo, and Dr. Jinghui Huang. Further studies will hopefully clarify the intricate connections among cellular processes, diseases, and potential drugs, paving the way for precise and efficient therapies. Reference Titles of original papers Metformin: A promising clinSical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52 Journal: Journal of Pharmaceutical Analysis DOI 1. 2. 3. Media contact Mengjie Wang [email protected] +86-(0)29-88960092 SOURCE Journal of Pharmaceutical Analysis (JPA)

Jessica Hambidge, head of regulatory affairs, LFH Regulatory, shares insight on digital health technologies for the US market and where we are today. There is a broad scope when we think about digital health, categories include mobile health (mHealth), health information technology (IT), wearable devices, telehealth and telemedicine and personalised medicine. The technology available is revolutionising healthcare to accurately monitor, diagnose, and treat disease. The FDA states that by using digital health tools, they can empower consumers to make better-informed decisions about their own health as well as providing new options for facilitating prevention and early diagnosis of life-threatening diseases, and management of chronic conditions outside of traditional healthcare settings. The regulatory perspective These advances have led the FDA to putting more focus and resources into Digital Health, including the creation of the Digital Health Centre of Excellence (DHCoE) which was formed in 2020. Digital Health Technologies (DHTs) have been creating a revolution in healthcare for many years, with the potential to benefit patients in ways that we are only just beginning to understand, one of which is the use of DHTs in drug development. In March of 2023, the FDA released a Framework for the use of DHTs in Drug and Biological product development which intends to address the challenges related to the use of DHTs in regulatory decision-making for drugs, such as data accuracy and reliability. DHTs used in drug development have not always fallen within the definition of a medical device, or the device is a low classification and hasn’t had thorough clinical testing, which can mean the appropriate evidence needed to prove effectiveness may not be available, resulting in the data collected from them cannot be used in any meaningful way. The new FDA Framework details the activities that the FDA will do in the coming years to provide clear guidance on the requirements for DHTs when they are intended to be used in regulatory decision making of drug development. DHTs can be used for remote data collection purposes in drug clinical studies with goals to continuously collect data from study participants and reduce the burden of study visits and increase recruitment rates, study population diversity and more. However, in order to use the data collected by the DHTs as endpoints in clinical studies, there needs to be appropriate evidence for the DHTs, proving the clinical effectiveness of the DHT and their measure, as well as how the DHT is maintained throughout the duration of the study. Currently DHTs are mostly used for exploratory endpoints only, DHT data has yet to be used for secondary or primary endpoints in more than a few successful clinical studies. The Framework lists several draft guidance’s that the FDA has released in recent years, including, ‘Digital Health Technologies for Remote Data Acquisition in Clinical Investigations’. This guidance places the responsibility on the sponsor of the clinical study to ensure that the DHT is fit-for-purpose, which includes a large number of topics to review, including design and validation. What does this mean for manufacturers of DHTS? This is where the manufacturers of the DHT can provide the highest benefit to the sponsors of the clinical study. If manufacturers of DHTs design and manage their DHTs in a similar way to high classification medical device development, even if their DHT isn’t a medical device, they will be able to provide the sponsor with most, if not all of the information required for the fit-for-purpose assessment, including a full validation package, processes and records of design, development and maintenance. The industry still has a long way to go before it becomes standard practice to use DHTs for regulatory decision making in drug development, but that doesn’t mean that it isn’t possible for manufacturers of DHTs to get a head start. The Framework and the guidance’s that will be developed in the next few years will provide further clarifications on how to develop DHTs moving forward and the work needed to be done for older products to be used for secondary and primary endpoints in clinical studies.