The development and application of nanoscale materials for tackling medical and health-related challenges is garnering considerable interest. By loading or attaching small molecule drugs in structure, these nanocarriers can improve the pharmacokinetic profile, toxicity, and therapeutic efficacy of cargos. This leads to unique advantages of nanomedicine in clinical results in comparison with conventional drugs. Nevertheless, numerous nanotherapeutics fail to prevent harm to healthy tissues due to their lack of specific accumulation and controlled drug release in disease sites. In this review, we briefly describe some common types of nanoparticles as drug delivery systems and present advanced approaches to improve circulation time and site-specific accumulation of nanoparticles. Then, the strategies for controlled drug release from nanocarriers upon differential internal and external stimulations are also discussed followed by the introduction of recently approval nanomedicines.
The segmentation of ischemic stroke lesions from Magnetic Resonance Imaging (MRI) images using deep learning (DL) techniques has emerged as a critical area of research in medical imaging. This article provides a comprehensive review of the current state-of-the-art methodologies in this domain, focusing on the advancements and challenges inherent in this field. Our review focuses on studies that utilize DL models for segmenting acute and sub-acute ischemic stroke lesions using MRI modalities. By systematically analyzing research from 2020 onward, we aim to clarify the advancements in the published models' effectiveness and provide a performance benchmark. This review stands out by comprehensively analyzing all the studies in this field, beyond the scope of prior reviews focused only on key publications. Additionally, this work serves as a comprehensive reference for researchers by compiling all relevant datasets, MRI modalities, evaluation metrics, loss functions, input data dimensionality, preprocessing, and augmentation techniques employed for this task. Additionally, we identify the challenges in this field and highlight the existing research gaps, in addition to proposing some directions for future work to enhance the effectiveness and accuracy of DL models in stroke lesion segmentation.
Systemic toxicity and off target effects are some of the major drawbacks of traditional, broad-spectrum therapies. Nanotechnology effectively counters these by offering precise, targeted alternatives and hence, reshaping biomedical engineering, therapeutics, diagnostics and even tissue regeneration. We explore six key nano-biomaterial platforms that exemplify this technological revolution. Silk fibroin nano-patches with engineered exosomes help diabetic wounds heal by producing collagen. Hydrogel activated with nanoparticle form nanoadhesives that bond well with wet environments, such as surgical sites. Graphene-based neural interfaces are characterized by high electrical conductivity with low immunogenicity. Bioelectronic-hydrogel composites adapt tissue mechanics for better physiological sensing. The pH-responsive metal-organic frameworks show remarkable potential in cancer treatment enabling targeted drug delivery, reducing harm to surrounding healthy tissue, and magnetic nanoparticles coated in cancer cell membranes improve natural killer-cell therapies. Despite these remarkable advances, the challenge of transition from laboratories to clinics faces many hurdles. Demands for scalable manufacturing techniques, strategies to suppress undesirable immune reactions and passing through safety and regulatory standards are some of the major challenges in Nanotechnology. Collaborative approaches from interdisciplinary fields like material science, biology, engineering and clinics may present a positive outlook to these issues. Nanotechnology can offer promising precision medicine tailored to an individual's safety and dosage profiles, minimising off target interaction risks.
Protein engineering (PE) has been applied to various medicines, food, and environments. Contributions of proteins have been reported with remarkable results in protein therapeutics, antibody engineering, enzyme synthesis, and more specific functions in industrial processes. Therefore, this chapter highlights the most recent PE advances in a battle against mainly human diseases and biomedical sciences. The application of PE will be reviewed, focusing on developing innovative techniques, including evolution, rational design, semi-rational design, and hybrid approaches to protein design in applications. In addition, we provide key achievements of PE in CRISPR/Cas systems, high-through data, and synthetic biology with updated results. Current challenges of using PE, ethical considerations, and various approaches for protein therapeutics are also discussed. In this chapter, the updated findings provide a comprehensive overview of the transformative potential of PE for researchers in the application areas of human disease, especially in cancer therapeutics.
IL-23, a cytokine involved in regulating immune system activity, plays an essential role in the development and progression of pain-associated inflammatory disorders. By promoting the differentiation and activation of Th17 cells, IL-23 induces the production of pro-inflammatory cytokines, including IL-17. These pro-inflammatory cytokines are key mediators of tissue damage and chronic inflammation observed in various conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. This chapter provides a comprehensive overview of the molecular mechanisms underlying IL-23-mediated inflammation and its role in the development of pain. Additionally, the therapeutic potential of IL-23 inhibition is examined, with a particular focus on immunotherapy, through the review of clinical data that supports the high efficacy of IL-23 blockade in reducing inflammation, alleviating symptoms, and improving patient outcomes. Targeting IL-23 is seen as a promising strategy for managing inflammatory diseases, providing an alternative to conventional therapies.
Glioblastoma (GBM) remains one of the most aggressive primary brain tumors, with a profoundly immunosuppressive microenvironment. Cytokines, chemokines, and growth factors are central to this immunosuppression, impairing the function of T cells, NK cells, dendritic cells, and promoting the recruitment of regulatory immune populations. Importantly, these soluble mediators also act directly on glioma cells, enhancing their proliferation, survival, invasion, and resistance to therapy. This chapter outlines the intricate network of cytokine-driven pathways in GBM, emphasizing their immunosuppressive functions and tumor-intrinsic effects, and discusses their implications for therapeutic intervention. Key factors such as TGF-β and IL-10 are highlighted for their dual roles in modulating immune responses and promoting tumor growth, while other cytokines, including IL-6, IL-1β, and CXCL12, contribute to a highly dynamic and redundant signaling environment. Type I and II interferons, traditionally seen as antitumoral, are shown to have paradoxical effects under chronic exposure, promoting immune exhaustion and inhibitory immune checkpoint upregulation. Given the complexity and adaptability of cytokine networks in GBM, single-target strategies have had limited success. Future therapies will need to adopt a systems-level approach, simultaneously disrupting multiple pathways and considering the spatial and temporal heterogeneity of the tumor microenvironment to achieve durable clinical responses.
Interleukin-10 (IL-10) is a key immunoregulatory cytokine with potent anti-inflammatory and immunomodulatory functions. Its pleiotropic effects and short half-life, however, have posed challenges for direct therapeutic use. To overcome these hurdles, diverse engineering strategies have been developed to enhance IL-10 stability, tailor its activity, and target its delivery. This review describes the major approaches to IL-10 modification, including fusion proteins (e.g. cytokine/cytokine fusion, IL-10-Fc fusions for half-life extension, and bispecific constructs), encapsulation systems (nanoparticles and hydrogels for sustained or localized release), protein engineering of IL-10 monomers/dimers to modulate receptor engagement (decoupling pro- vs anti-inflammatory signaling), targeted delivery methods (antibody-mediated tissue targeting and intestinal-specific release), and receptor-based fusion proteins (immunoadhesins) to modulate IL-10 signaling. For each strategy, we highlight representative preclinical studies and clinical programs, examining pharmacodynamics, pharmacokinetics, efficacy in disease models (cancer, autoimmunity, colitis, fibrosis, transplantation), and translational potential. Advantages and limitations such as immunogenicity, delivery efficiency, and scalability are critically discussed. These advances collectively illustrate how bioengineering is unlocking IL-10 therapeutic potential while mitigating its prior limitations, paving the way for next-generation cytokine immunotherapies.
Interferon-gamma (IFN-γ) is a pivotal cytokine that coordinates the immune response to infections caused by viruses and intracellular pathogens. Knockout (KO) mice lacking IFN-γ exhibited a significant reduction in the capacity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to eliminate tumor cells, resulting in accelerated tumor growth and metastasis. These findings underscore the key role of IFN-γ in regulating the antitumor immune response. However, many advanced tumors exhibit dysregulated IFN-γ signaling, which exerts direct protumoral and immunosuppressive effects, thereby allowing cancer cells to evade immune surveillance and promoting cancer progression. This dual role of IFN-γ in regulating cancer immunity has limited its therapeutic use in cancer. Understanding the specific conditions under which IFN-γ has an antitumoral or a protumoral role is a challenge for optimizing its use in cancer therapy.
Three-dimensional (3D) bioprinting has come a long way to have emerged as a transformative technology in bio-fabrication. Bioinks with specific attributes of cellular compatibility, mechanical strength, printability, and biodegradability remain crucial factors and yet a critical challenge. More growth in bioinks is happening with 4D bioprinting due to new developments in supramolecular hydrogels and both naturally and artificially made polymers. iPSCs, organ-on-chip technologies, and microfluidics allow scientists to produce sensitive tissue used for drug therapy and diagnosing diseases. Extrusion, inkjet, and stereolithographic printing let 3D bio-printers mix several materials, preserve cells, and create highly detailed prints. Despite the differences and similarities of AI and automation, they can both be valuable for ensuring quality control. Concerns that limit the clinical use of 3D bioprinting involve regulations, the uneven consistency of bioink, and the importance of ensuring long-term security. It is essential to develop platforms for bioprinting that are scalable, reasonably low-cost, and GMP-compliant and to maintain close collaboration among different fields to achieve all that personalized regenerative medicine and clinical care for cancer, heart disease, neurological diseases, and similar illnesses can offer.
Understanding the pathologies related to neurological issues, viz. Alzheimer's disease (AD), brain tumors, and multiple sclerosis (MS) are complex and still lack effective therapeutics. Management of the global health burden caused by the escalating cases of neurodegenerative diseases urgently requires early and precise diagnosis. While conventional diagnostic tools like X-ray, Computed Tomography (CT), and Electrophysiological Techniques still hold a crucial role in the field of neurodiagnosis, researchers and clinicians are searching for advancements and the development of cutting-edge tools to enhance diagnostic accuracy, early detection, and improved health outcomes. Some later developed tools like PET and fMRI have proven beneficial in diagnosing the structural and functional aspects of neurological pathologies. However, specific and differential diagnosis for different neurodegenerative diseases is critical. We discuss how Omics studies (including proteomics and genomics), Artificial Intelligence (AI), and Machine learning (ML) have further enhanced the advancements in the field of neurodiagnostics. Our chapter highlights the importance of identifying novel blood-based, cerebrospinal fluid (CSF) based biomarkers while giving emphasis to developing non-invasive biomarkers to uplift the field of neurodiagnosis. The chapter concludes that the importance of the development of advanced bioimaging, multi-omics studies, computational studies, and exploring futuristic technologies, including the development of biosensors, can pave the path for next-generation neurodiagnostic techniques.
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and redox imbalance. It has emerged as a pivotal mechanism implicated in various diseases, including cancer, chronic kidney diseases (CKD), neurodegenerative disorders, pulmonary fibrosis, chronic wounds, and viral infections such as COVID-19. This chapter presents a comprehensive overview of the molecular underpinnings of ferroptosis, emphasizing its key regulators-iron metabolism, lipid peroxidation pathways, and antioxidant defenses such as GPX4 and system Xc-. We explore recent advances highlighting the therapeutic potential of ferroptosis modulation across multiple pathological contexts. In cancer, ferroptosis inducers have shown efficacy in overcoming drug resistance and enhancing immunotherapy. In contrast, inhibition of ferroptosis offers protective effects in neurodegenerative diseases, ischemia-reperfusion injury, and chronic inflammatory conditions. Applications in nanomedicine have further enabled targeted delivery of ferroptosis modulators, expanding their clinical relevance. The chapter also discusses emerging roles of ferroptosis in wound healing, CKD and pulmonary fibrosis, with particular attention to COVID-19-related lung injury. Finally, we evaluate current therapeutic strategies, safety considerations, and potential clinical applications, along with future directions including biomarker development and personalized medicine. Our aim is to provide a unified perspective on ferroptosis as a disease-modifying mechanism and to highlight its growing importance as a therapeutic target across diverse clinical disciplines.
Autophagy is a fundamental cell biological process that controls the quality and quantity of the eukaryotic cytoplasm. Dysfunctional autophagy, when defective or excessive, has been linked to human pathologies. Autophagy can randomly degrade cytoplasmic components in a non-selective manner commonly referred to as bulk autophagy. In contrast, selective forms of autophagy specifically target cytoplasmic structures such as organelles thereby being important for cellular quality control and organelle homeostasis. Recent studies demonstrate the role of bulk and selective autophagy in the integration of physical constraints. Mechanical forces, combine with biochemical signals control the development and the physiological functions of different organs and can also contribute to the progression of various diseases. The aim of this Review is to summarize and discuss our current knowledge on the role of autophagy in regulating a broad range of cellular responses, from morphology, metabolism, to inflammation and senescence, in the context of mechanical forces. Additionally, where relevant, we will also discuss the potential implications of mechanical stress-induced autophagy in pathologies.
Exercise induces profound mitochondrial adaptations in skeletal muscle, with different modalities uniquely influencing different branches of mitochondrial quality control (MQC). This review examines how endurance, resistance, and high-intensity interval training (HIIT) regulate mitophagy, the selective degradation of damaged mitochondria, in skeletal muscle (SkM). Research in rodents has shown that endurance exercise upregulates mitophagy primarily through the AMPK/PGC-1α signaling axis, promoting mitochondrial turnover and ensuring metabolic efficiency. In humans, high-intensity exercise increases mitophagy to a larger extent when compared to traditional endurance exercises. On the other hand, resistance exercise triggers alternative MQC mechanisms, including potential mitochondrial ejection. Collectively, these results suggest that mitophagy and MQC pathways are regulated in human SkM following exercise, but the specific molecular pathways seem to be specific to each exercise mode. Future studies should aim at disentangling the multiple mitophagy and MQC pathways in human SkM following exercise.
Autophagy is a process which is responsible for the maintenance of cellular homeostasis. This is achieved through the orchestration of both highly selective and non-selective degradation pathways, the purpose of which is the elimination of damaged structures. Recent findings have revealed that, in addition to its intracellular function, this organelle exhibits a remarkable "social life" and forms relationships with other cellular organelles. This has led to the discovery that mitochondrial quality is maintained not only through mitophagy, but also through extracellular mechanisms between cells. This has significantly expanded our understanding of tissue integrity. In skeletal muscle, autophagy, or autophagy, is a finely tuned process that plays a crucial role in maintaining physiological performance and adaptation. Disruption of autophagy has been linked to accelerated degeneration, metabolic dysfunction, and frailty. Although therapeutic manipulation of autophagy and mitophagy shows promise in restoring muscle health, major translational barriers persist. A more profound and nuanced exploration of autophagy flux in human muscle is imperative, underpinned by novel advanced cell biology technologies and predicated on satellite cells as the primary agents in muscle regeneration. The full therapeutic potential of autophagy could be harnessed to redefine interventions against muscle ageing and associated diseases. However, this would still require critical scrutiny of the long-term effects and systemic consequences.
