Progress in molecular biology and translational science最新文献

Epigenetic drug discovery has become an integral part of medicinal chemistry in the past two decades. Targeting epigenetic proteins-enzymes that modify histone proteins and DNA (writers and erasers) and proteins that recognize such modifications (readers)-has been firmly established as a medicinal strategy for treatment of many human diseases, including cancer and neurological disorders. In this chapter, we systematically describe peptide-based inhibitors of structurally and functionally diverse classes of epigenetic proteins. We show that epigenetic writers, such as DNA methyltransferases, histone methyltransferases and histone acetyltransferases, can be efficiently inhibited by peptides possessing nonproteinogenic amino acids. Moreover, the activity of epigenetic erasers, including TET enzymes, histone demethylases, and histone deacetylases, can be selectively modulated by diverse linear and cyclic peptides. Furthermore, we discuss chromatin-binding epigenetic reader proteins that can be inhibited by histone-mimicking peptides. Overall, this chapter highlights that peptides provide an important molecular platform for epigenetic drug discovery programmes in academia and industry.

Alcohol use disorder (AUD) is a substantial public health issue, with few treatment choices and a high social cost. This review investigates the possibility of peptide pharmacology as a new treatment for AUD. Peptides, or short chains of amino acids, provide specific manipulation of neuronal pathways involved in addiction, such as the opioid, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), and glutamate systems. Preclinical research has shown that peptide-based therapies can reduce alcohol intake, demand, and relapse in animal models of AUD. Opioid peptides like β-endorphin and enkephalins affect alcohol reward processing by interacting with µ, ∂, and κ opioid receptors. CRF peptides reduce stress-induced alcohol-seeking behavior by targeting the dysregulated CRF system. NPY and associated peptides reduce cravings and anxiety by regulating stress and emotional processing. Peptide-based therapies have strong translational potential, as evidenced by early clinical trial results. There are also challenges in converting preclinical discoveries into clinical practice, such as establishing the safety, tolerability, and effectiveness of peptide therapies in humans. Future initiatives include identifying new peptide targets, optimizing pharmacokinetics, and incorporating peptide-based therapies into established therapy methods. Overall, peptide pharmacology represents a potential prospect in AUD therapy, as it provides tailored therapies that address the complex neurobiological pathways that underpin addiction.

Biomarkers are vital indicators of biological processes and play a key role in diagnostics and personalized medicine. This chapter discusses the classification of biomarkers and presents an overview of biosensing technologies developed for their detection through wearable, ingestible, and implantable sensor platforms. Wearable sensors mainly track physiological signals, such as heart rate and temperature, and are increasingly capable of detecting biochemical markers in sweat or interstitial fluid. Ingestible sensors provide non-invasive access to the gastrointestinal tract, detecting biomarkers like pH, gases, and metabolites to assess systemic health. Implantable sensors, integrated into body tissues, enable long-term, high-resolution monitoring of internal biomarkers. The future of biosensing lies in multi-modal platforms that combine various sensing technologies with AI-driven data analysis to enhance diagnostic precision and support personalized treatments. However, despite significant advancements, several challenges remain, including ensuring sensor biocompatibility, managing power requirements, securing health data, navigating regulatory approvals, and addressing ethical concerns. Overcoming these barriers is essential for successful clinical translation and broader commercialization.

Wearable biosensors offer real-time, non-invasive monitoring of vital physiological and biochemical signals, transforming the landscape of personalized healthcare. This chapter outlines the components and the ideal requirements for usability, such as flexibility, comfort, and biocompatibility. They are employed in diverse applications such as chronic disease management, including diabetes, respiratory conditions, neurological disorders, cancer detection, infectious disease tracking, and stress monitoring. These sensors support early diagnosis, continuous monitoring, and personalized treatment strategies. The integration of artificial intelligence enhances data interpretation, enabling predictive insights and real-time alerts. However, with increased data collection comes the need for strong privacy and security protections. Wearable biosensors hold significant promise in reshaping healthcare by enabling proactive, data-driven decision-making and improving health outcomes through continuous and personalized monitoring, which has been highlighted in this chapter.

Recent advances in next-generation biosensors are transforming on how infectious diseases are monitored and offering rapid, real-time, highly sensitive detection of pathogens. Emerging platforms such as wearable, ingestible, and implantable biosensors are enabling continuous health tracking and facilitating early diagnosis, which is critical in managing outbreaks and preventing disease progression. Innovations in nanotechnology, electrochemical sensing, and machine learning are further enhancing the precision, scalability, and affordability of these tools. Biosensors hold particular promise for infectious disease surveillance, especially in low-resource environments where traditional diagnostics may be slow, costly, or unavailable. These technologies can support timely outbreak response, antimicrobial resistance tracking, and personalized treatment strategies. Despite these promising developments, several challenges like regulatory approval processes, limited access to research funding, and difficulties in integrating new biosensing technologies into existing healthcare infrastructure continue to hinder widespread adoption. Overcoming these barriers will require interdisciplinary collaboration among engineers, clinicians, public health experts, and data scientists. This chapter explores key technological breakthroughs, implementation challenges, and the expanding role of biosensors in public health. It also examines future directions and opportunities for strengthening infectious disease monitoring systems to improve patient outcomes and reinforce global health resilience.

Biosensors and devices that are wearable and enable continuous monitoring of lung function are disrupting methods of tracking respiratory health outside conventional settings. These cutting-edge technologies combine state-of-the-art sensors, flexible materials, and wireless connectivity to continuously monitor important respiratory metrics like oxygen saturation, breathing patterns, and lung volumes. They hold considerable promise in the eclipse of chronic respiratory diseases such as asthma and Chronic obstructive pulmonary disease (COPD), early detection of exacerbations, and individualization of treatment. Outside the clinical realm, these wearable biosensors provide actionable insights on improving respiratory efficiency and patterns that can be utilized in fitness optimization, rehabilitation, and sleep disorder management. Recent progress in sensor miniaturization, biocompatible materials, and data analytics has improved the comfort, accuracy, and ease of usability of these devices. Although these advantages exist, issues of motion artifacts, sensor calibration, and data security remain an ongoing challenge. What artificial intelligence and Internet of Things (IoT) allow us to do is break down these barriers, so no longer is it just a promise of predictive analytics and remote monitoring but actually a seamless possibility. Moreover, wearable biosensors may also be beneficial in public health programs as they allow large-scale collection and monitoring of individual health data at population levels during epidemics. As these devices progress, they will revolutionize respiratory healthcare by developing excellence in treatment, providing increased accessibility, and enabling proactive management of the disease.

Ingestible biosensors are a mix of advanced biomedical engineering, digital health and precision pharmacotherapy. These miniaturised electronic devices are encapsulated in biocompatible materials, which operate within gastrointestinal (GI) tract. This enables real-time monitoring of pharmacological and physiological parameters. The development of modern FDA-approved platforms such as SmartPillTM and IntelliCapTM, from early radio pills, has been outlined, showing the advancements in sensor integration, wireless telemetry and microelectronics. The main purpose of such pills includes detection of pharmacokinetic profiles, monitoring of metabolic biomarkers like glucose, lactate and volatile gases and verification of real-time medication ingestion. Such kind of applications are critical in behavioural medicine, forensic toxicology, clinical pharmacology and chronic disease management. The chapter discusses core engineering aspects of a capsule, such as data transmission technology, sensor modules and power systems. Advancements such as biodegradable capsules, AI-integrated analytical platforms and biofuel-powered sensors are discussed in relation to next-generation health care systems. Every advance technology comes its fair share of challenges such as power limitations, patient acceptance, signal attenuation and ethical concerns surrounding data privacy. Predictive diagnostics and decentralised care are also analysed, keeping in view the merger of biosensor data with AI and Big Data platforms. The chapter concludes by focusing on possible contributions of ingestible biosensors in the frontier of personalized and preventive medicine, this can redefine diagnostics, drug delivery and remote monitoring. These devices will transition from clinical novelty to standard instruments for care for various therapeutic landscapes.

Data gathering for diagnostic purposes often relies on psychological instruments and validated tests applied individually through in person interviews. Such an approach is limited since it relies on a subjective perception of the individual as well as their abilities to recall information concerning their behaviors, thoughts, and feelings. Thus, the accuracy of the assessment tends to be unreliable and prone to bias, stigma, as well as subjective interpretations. Moreover, psychological instruments (such as questionnaires) are often created and validated for a specific population. However, socio-demographic differences, along with cultural, environmental, and educational aspects, are factors that strongly influence the reliability of tests and their results. On the other hand, wearable technology has a promising potential to address such limitations, being well suited for mental health applications. Wearables are capable of capturing physiological and behavioral measures from human users, reducing subjectivity in this process. Wearable biosensing devices are also particularly useful for capturing users' data longitudinally in a non-invasive and unobtrusive way. Physiological data from wearable sensors includes pulse rate, skin conductance, skin temperature, cortisol levels, and respiration rate. Wearable sensors can also detect behavioral data such as sleep patterns, physical activity, and social interactions. These data points combined have proven to be highly effective in detecting an individual's stress, attention, and mood. Hence, studies in mental health, wellness, and stress have increasingly adopted wearable technologies. This chapter provides a comprehensive review of wearable devices and their widespread application for mental health, wellness, and stress management. We cover various form factors, sensors, data analysis techniques and real-world applications. We conclude with a discussion about the best practices, design considerations and future directions to deploy wearable applications that are ethical and fair for users.

Monitoring skeletal muscle contraction provides valuable information about the muscle mechanical properties, which can be helpful in various biomedical applications. This chapter presents a single-element flexible and wearable ultrasonic sensor (WUS) developed by our research group and its application for continuously monitoring and characterizing skeletal muscle contraction. The WUS is made from a 110-µm thick polyvinylidene fluoride piezoelectric polymer film. The lightweight and flexible properties of the WUS enable stable attachment to a skin surface without impacting the tissue motion of interest beneath the WUS. As an example of in-vivo demonstrations of muscle contraction monitoring and characterization, continuous monitoring of muscle contraction of the lateral head of the triceps muscle in healthy human subjects is performed using the WUS in the ultrasound pulse-echo technique. The changes in tissue thickness caused by muscle contraction evoked by electromyostimulation (EMS) at different EMS pulse repetition frequencies are measured using an ultrasound time-of-flight method. The muscle contractile parameters are estimated using the muscle twitches obtained at an EMS frequency of 2 Hz, where the muscle can fully relax between consecutive twitches. Furthermore, a level of tetanic progression, where the muscle cannot completely relax, is quantitatively assessed using the fusion index (FI), estimated from the changes in tissue thickness at EMS frequencies ranging from 2 Hz to 30 Hz, with an increment of 2 Hz. It is demonstrated that the unfused and fused tetanus frequencies can be estimated from the FI frequency curve and the contractile parameters obtained at 2 Hz. The WUS and ultrasonic methods demonstrated in this study could be valuable for non-invasive, continuous monitoring of skeletal muscle contractile properties.

The administration of therapeutic proteins directly to the eye is a major breakthrough in the treatment of several eye conditions. This chapter highlights the crucial significance of ocular therapies because of the widespread occurrence of vision-threatening disorders and the distinct difficulties presented by the eye's architecture and physiological limitations. Therapeutic proteins, known for their exceptional specificity and effectiveness, provide hopeful answers. However, they encounter various obstacles in their ocular distributions like tear film, corneal epithelium, and blood-retinal barrier etc. Formulation techniques and drug delivery technologies, such as nanotechnology, hydrogels, microneedles, liposomes, dendrimers, and polymeric nanoparticles are improving the stability, bioavailability, and targeted administration of proteins. Notwithstanding this progress, obstacles such as protein stability, immunogenicity, and patient compliance endure. Methods to address these challenges include improving permeability, formulating sustained release systems, applying non-invasive delivery techniques, and implementing tailored delivery strategies. Furthermore, it is essential to effectively navigate through regulatory routes, comprehensively grasp market factors, and successfully secure intellectual property to achieve successful commercialization of these new methods.