搜索结果：Therapeutic innovation & regulatory science

No country is fully self-sufficient in meeting its pharmaceutical needs; yet significant disparities exist in export-import trade balances across nations. Ethiopia relies on pharmaceutical imports, exposing the health system to supply vulnerabilities and challenges in ensuring access to essential medicines. Addressing these challenges requires balanced policy frameworks and robust regulatory support to ensure consistent access, quality, and affordability of medicines. Within this context, the present study assessed the state of pharmaceutical imports in Ethiopia, and explored importers' perspectives on the business environment and the national regulatory system. An online survey-based descriptive study design was employed to assess the views and experiences of 78 eligible professionals working in pharmaceutical import companies. Stratified random sampling was utilized to choose the import firms. Data were analysed using SPSS version 26, with reliability and internal consistency tests performed. Descriptive statistics were used to summarize and interpret the findings. Seventy-one participants (91%) completed and returned the survey. The majority of respondents (74.4%) represented private limited companies and represented multiple foreign manufacturers primarily based in Asia (78.9%) and Europe (54.9%). The most commonly imported products were antimicrobials, analgesics, and medicines for gastrointestinal and cardiovascular diseases. Most respondents (77.4%) characterized the pharmaceutical import environment as unpredictable or recessionary, citing key challenges such as foreign currency shortages, policy-related barriers, and protracted regulatory processes. A substantial majority (77.5%) of respondents rated the capacity and performance of EFDA as good or very good, while 56.3% viewed the regulatory framework as favourable for pharmaceutical importation. Over one-third rated regulatory instruments as acceptable across most of the assessment criteria. Nevertheless, several challenges were identified, including inadequate stakeholder engagement, operational inefficiencies, limited transparency and ethical concerns, and insufficient technical expertise among reviewers, all of which were reported to undermine the effectiveness of the regulatory system. Given the healthcare system's dependence on reliable access to quality-assured medicines, balanced policy, and regulatory support are required to strengthen the pharmaceutical import sector, alongside the efforts to build local manufacturing capacity. The findings underscore the need for strategic improvements in both the business and regulatory frameworks such as coherent industrial and health policies, targeted financing mechanisms, expedited risk-based regulatory services, robust domestic manufacturing, and enhanced ethical standards, to optimize access to essential healthcare products.

Rare diseases, affecting approximately 8% of the global population, remain among the most underserved areas in modern medicine due to their low prevalence, complex genetic origins, and limited commercial incentives for drug development. Rare neurological disorders, in particular, pose formidable challenges owing to their progressive nature and the difficulty of delivering thera-peutics across the blood-brain barrier. This review explores the emerging role of nanomedicine in transforming rare disease management through precision-targeted drug delivery, enhanced bioavail-ability, and the ability to bypass biological barriers. Nanoparticles (NPs)-including PEGylated NPs, lipid-based NPs, polymeric NPs, and hybrid formulations-are being engineered to deliver therapeu-tic agents for gene therapy, enzyme replacement, and RNA interference. These platforms have shown promise in treating conditions such as Krabbe disease, Niemann-Pick type C1, spinocerebel-lar ataxia type 1, and prion diseases. Additionally, nanotherapeutics are being investigated for pulmonary and congenital lung disorders, including cystic fibrosis and idiopathic pulmonary fibro-sis, with improved tissue penetration and reduced systemic toxicity. The review also highlights the potential of AI-integrated diagnostics and personalized nanomedicine to address disease heterogene-ity and improve patient outcomes. Despite these advances, significant barriers remain, including regulatory complexity, high development costs, and limited clinical models. The manuscript calls for collaborative innovation across academia, industry, and regulatory bodies to accelerate clinical translation and ensure equitable access. By bridging molecular innovation with patient-centric care, nanotherapeutics offer a paradigm shift in the diagnosis and treatment of rare diseases, potentially redefining therapeutic landscapes and improving the quality of life for affected individuals.

Thiocolchicoside is a colchicoside compound that is partly synthetic and is most known for its characteristics of centrally acting muscle relaxants. It has been widely used in the management of musculoskeletal disorders due to its ability to modulate inhibitory neurotransmission. Recent research has shown potential in additional therapeutic domains, such as antimicrobial, anticancer, and anti-inflammatory. The objective of this review is to provide a comprehensive overview of the chemical profile of thiocolchicoside, including how it works, pharmacokinetics, traditional and novel therapeutic uses, safety concerns, and recent advances in drug delivery systems. Special emphasis is given to its emerging roles in oncology and infectious disease management. Relevant literature was collected from PubMed, Scopus, Google Scholar, and other scientific databases. Preclinical and clinical studies, review articles, case reports, and regulatory documents related to thiocolchicoside were reviewed to extract updated and critical information. Thiocolchicoside exerts its effects by acting as a competitive antagonist on gamma-aminobutyric acid type A (GABA-A) and glycine receptors, leading to muscle relaxation without strong sedation. Several preclinical studies suggest anti-inflammatory, analgesic, antimicrobial, and cytotoxic potential. Recent innovations include nanogel-based formulations and other targeted delivery systems to enhance bioavailability and reduce systemic toxicity. However, concerns remain regarding its genotoxicity and myelosuppressive effects, particularly at higher doses or with prolonged use. Thiocolchicoside remains a valuable agent in pain and spasm management, but its expanding therapeutic spectrum suggests opportunities for drug repurposing, especially in oncology and infectious disease. Future research ought to concentrate on safety optimization, chronic toxicity studies, and the development of novel delivery platforms to maximize therapeutic efficacy while minimizing risks.

Angiogenic-osteogenic coupling is the temporal and spatial interplay between osteogenesis and angiogenesis, profoundly influenced by the immune microenvironment. Extracellular vesicles (EVs), regarded as crucial signaling mediators in bone development, are widely present in immune networks. However, their critical immunomodulatory roles in the coordinated angiogenic-osteogenic coupling process remain insufficiently elaborated. This article reviews their immunomodulatory mechanisms in physiological and pathological angiogenic-osteogenic coupling and summarizes their clinical translation potential. It systemically reveals the sophisticated regulatory network through which EVs orchestrate angiogenic-osteogenic coupling via immune organs, cells, and factors, specifically highlighting the underlying molecular mechanisms. The immunomodulatory mechanism and clinical translational potential of EVs in bone disorders are further examined. Notably, pioneering breakthroughs in engineering exosomes to enhance angiogenesis and osteogenesis are introduced, bridging fundamental research and clinical application. Understanding the interactions between EVs' immunomodulatory effects and angiogenic-osteogenic coupling provide significant insights into future research directions and novel therapeutic strategies for bone regeneration.

The homeostasis of bone metabolism relies on the precise synergistic regulation among osteoblasts, osteoclasts, and osteocytes. Disruption of this regulatory network underlies the pathogenesis of osteoporosis, osteonecrosis, osteoarthritis, and other metabolic bone diseases. As an emerging mode of intercellular communication, mitochondrial transport delivers functional mitochondria to impaired cells, thereby reshaping cellular metabolism, alleviating oxidative stress, and restoring cell function. It thus plays an irreplaceable role in maintaining bone metabolic homeostasis. However, studies focusing on mitochondrial transport in bone metabolism are lacking, and the underlying molecular mechanisms have not been elucidated. For metabolic bone diseases, many bottlenecks exist in clinical translation. This review comprehensively summarizes the core molecular mechanism involved in mitochondrial transport, its regulatory functions in bone metabolism homeostasis, its association with metabolic bone diseases, and intervention strategies targeting mitochondrial transport. We aim to provide novel insights into the mechanism and targeted therapy of metabolic bone diseases.

Myocardial infarction (MI) initiates a biphasic immune response, which plays a critical role in determining whether the heart undergoes adaptive repair or progresses to pathological fibrosis. Traditional drug and gene therapy delivery systems have been insufficient in precisely modulating this intricate sequence of events in both temporal and spatial dimensions. In recent years, nucleoside-modified messenger RNA (mRNA) technology, encapsulated within lipid nanoparticles (LNPs), has emerged as a novel platform for delivering transient, non-integrating, and repeatable immune modulation to the injured heart. This article will explore recent interdisciplinary advancements in mRNA technology and cardiac immunology from five distinct perspectives. (i) Strategies for mRNA design, encompassing nucleoside modifications and purification techniques, are primarily aimed at circumventing detection by innate immune sensors within inflamed myocardial tissue; (ii) The concept of trained immunity is investigated, focusing on how transient expression of mRNA encoding epigenetic editors may potentially erase pathological epigenetic imprints in myeloid progenitor cells; (iii) Immune cell reprogramming is examined, addressing the myeloid lineage through macrophage polarization and the degradation of neutrophil extracellular traps via metabolic and transcriptional reprogramming, as well as the lymphoid lineage through transient CAR-T cells, in situ-induced regulatory T cells, and regulatory B cells, with an emphasis on the role of cardiomyocytes as paracrine signaling hubs; (iv) The optimization of lipid nanoparticle (LNP) delivery technology is discussed, including SORT-based organ-targeting strategies and the immunogenicity challenges faced by lipid carriers in ischemic tissues, alongside the development of next-generation self-amplifying RNA payloads; (v) Standards for clinical translation are outlined, involving representative pipelines such as AZD8601 and mRNA-0184, strategies for repeated dosing from an immunological perspective, and the use of biomarkers to guide precision dosing timing. In conclusion, we propose an innovative framework that integrates spatial transcriptomics, gender-stratified dosing strategies, and multi-mRNA formulation technology, with the objective of establishing a viable pathway for personalized cardiac immune reprogramming.

Interleukin-6 (IL-6) is a cytokine with multiple biological effects. It plays a complex and seemingly paradoxical central role in both the physiological homeostasis and pathological processes of skeletal muscle. Under physiological conditions, particularly during acute exercise, IL-6 produced and secreted by the contracting skeletal muscle itself acts as an important "myokine." It operates in an autocrine, paracrine, or endocrine manner to regulate systemic energy metabolism, insulin sensitivity, muscle regeneration, and adaptive hypertrophy. This function is crucial for the health benefits conferred by exercise. However, under various pathological conditions-such as cancer cachexia, sepsis, muscular dystrophy, denervation, disuse atrophy, and chronic inflammatory diseases-persistently elevated systemic or local IL-6 levels become a key mediator driving skeletal muscle atrophy, metabolic disorders, and functional decline. This review systematically elaborates on the dual role of IL-6 in skeletal muscle. It provides an in-depth analysis of its downstream signaling pathways (e.g., JAK/STAT, gp130, MAPK, PI3K-Akt) and upstream regulatory mechanisms (e.g., the Piezo1/KLF15 axis, calcium signaling, mitochondrial function, oxidative stress). A particular focus is placed on discussing the distinct biological effects of classical IL-6 signaling versus trans-signaling. Furthermore, we address current challenges in research and practice, including the cell specificity of IL-6 signaling, the complexity of its temporal regulation, the definition of physiological versus pathological concentrations, discrepancies between animal models and human diseases, and the plasticity of its function across different pathological contexts. Finally, this review explores the potential of targeting the IL-6 signaling pathway as a therapeutic strategy for skeletal muscle atrophy and related metabolic diseases. Potential interventions include IL-6/IL-6R monoclonal antibodies, JAK/STAT inhibitors, gp130 modulators, exercise interventions, and nutritional strategies. This aims to provide a theoretical foundation and novel perspectives for future translational research and clinical interventions.

Pulmonary fibrosis (PF) is a progressive and often fatal interstitial lung disease for which the currently available pharmacological therapies remain largely limited to slowing disease progression rather than reversing established fibrosis. This limitation has stimulated increasing interest in innovative therapeutic platforms capable of modulating complex fibrotic pathways. In this context, exosomes-nanoscale extracellular vesicles-have emerged as promising cell-free nanocarriers due to their intrinsic biocompatibility, low immunogenicity, and ability to be engineered for targeted drug delivery. In this review, we provide a comprehensive overview of both natural and engineered exosome-based strategies for the diagnosis and treatment of pulmonary fibrosis. We summarize recent advances in exosome engineering, including ligand functionalization, glycoengineering, and therapeutic cargo loading, highlighting how these approaches may support the development of more targeted and potentially personalized nanotherapeutic strategies. We further discuss emerging hybrid delivery platforms, such as exosome-liposome chimeras and hydrogel-based depots, which may enhance pulmonary retention, improve therapeutic durability, and enable controlled drug release. Finally, we outline key challenges and opportunities for clinical translation, including large-scale manufacturing, regulatory considerations, and clinically relevant delivery routes such as inhalation-based administration. Collectively, this review provides a translational perspective on engineered exosomes as emerging nanotherapeutic platforms for pulmonary fibrosis.

Proteolysis-targeting chimeras (PROTAC) are an innovative treatment approach that selectively breaks down disease-relevant proteins by utilizing the ubiquitin-proteasome system. Other than PROTAC, Molecular glue, Lysosome-Targeting Chimaera (LYTAC), GlueTAC, Autophagy-Targeting Chimaera (AUTAC), Autophagosome Tethering Compound (ATTEC), and Antibody-based PROTAC (AbTAC) are emerging targeted protein degradation (TPD) techniques, of which PROTAC offers several benefits. This review discusses the development of proteolysis-targeting chimeras (PROTACs) for targeted protein degradation, highlighting their mechanism of action via the ubiquitin - proteasome system. It examines key physicochemical and pharmacokinetic challenges that limit clinical translation. Advanced formulation strategies, including nanoformulations and amorphous solid dispersions, prodrug improve solubility, bioavailability, and therapeutic efficacy. Additionally, characterization techniques are summarized, and the review outlines recent progress and critical considerations for the successful clinical translation of PROTAC-based therapeutics. Relevant articles from PubMed, Scopus, and Web of Science, spanning publications up to 2026, were gathered. PROTACs represent a transformative therapeutic modality, enabling selective protein degradation beyond conventional inhibition. Future research should focus on improving bioavailability, targeted delivery, and stability, while advancing prodrug strategies, E3 ubiquitin ligase selectivity, oral formulations, and predictive models for clinical translation. Additionally, it should emphasize scalable manufacturing, regulatory frameworks, and integration with emerging targeted protein degradation technologies.

Myocardial infarction (MI) initiates a rapid and highly coordinated immune response that is essential for the clearance of necrotic tissue and activation of reparative processes. However, prolonged or dysregulated post-MI inflammation can exacerbate myocardial injury, promote adverse cardiac remodeling, and ultimately contribute to heart failure. Although current therapeutic strategies improve survival and symptom management, they remain limited in their ability to restore lost cardiomyocytes or effectively modulate the post-infarction immune microenvironment. In this context, stem cell-derived extracellular vesicles (EVs) have emerged as promising cell-free therapeutic candidates due to their immunomodulatory, regenerative, and paracrine properties. These nanoscale vesicles carry a diverse cargo of bioactive molecules, including microRNAs, proteins, lipids, and other signaling mediators that regulate intercellular communication and tissue repair. EVs derived from mesenchymal stem cells, cardiac progenitor cells, and induced pluripotent stem cells have demonstrated the ability to modulate key immune pathways by attenuating neutrophil-mediated inflammatory injury, promoting macrophage polarization towards a reparative M2 phenotype, and regulating T-cell responses by suppressing pro-inflammatory activity while enhancing regulatory T-cell function. Collectively, these effects help restore immune homeostasis and reduce adverse cardiac remodeling following MI. Moreover, advances in EVs engineering, cargo modification, and targeted delivery systems may enhance their therapeutic efficacy and translational potential. However, several critical challenges, including large-scale production, cargo heterogeneity, and the lack of standardized protocols for isolation and characterization, still need to be addressed before successful clinical translation. This review summarizes the current understanding of stem cell-derived EVs biology, comparative advantages over conventional and cell-based therapies, and their immunomodulatory mechanisms in post-MI repair. Moreover, it highlights recent innovations and the major challenges that must be addressed for successful clinical translation.

Drug repurposing is often promoted as a faster, lower-risk alternative to de novo discovery, yet substantial barriers continue to limit successful implementation. We performed a scoping review of articles included in PubMed and ScienceDirect with the aim to identify and categorize challenges and analyze the intersections between them. Our review included 73 articles which revealed scientific, clinical, regulatory, economic, and implementation barriers, with the principal being the clinical translation of generated candidates. Scientific challenges include the necessity for new Phase II/III trials to validate efficacy, safety, and optimal dosing in new therapeutic contexts. Across disease areas, domain-specific barriers include subgroup-dependent responses in oncology, resistance and penetration challenges in anti-infectives, and data scarcity in rare diseases. Computational and AI-assisted approaches face fragmented data, model robustness, and insufficient validation. In addition, off-patent drugs face evidence requirements as rigorous as those for de novo entities, yet lack the market exclusivity incentives required to attract private investment. Additionally, an "institutional bottleneck" hinders academic researchers from bringing findings "on-label" due to a lack of regulatory infrastructure and collaborative frameworks. We conclude that drug repurposing requires a distinct translational paradigm involving multi-stakeholder collaboration and early regulatory engagement to bridge the gap between laboratory discovery and patient access.

The advent of liposomal amphotericin B (L-AmB, commercialized as AmBisome) technology represented a paradigm shift in antifungal drug delivery, substantially reducing the severe, well-known nephrotoxicity historically associated with the conventional deoxycholate formulation (D-AmB). Despite this advance, the expiration of the innovator's patent has spurred the global development of generic liposomal preparations, raising critical biopharmaceutical and clinical safety concerns. This article reviews the literature and regulatory landscape of L-AmB and its nanosimilars. A comprehensive search was performed using PubMed, Embase, and Web of Science (1990-2026), focusing on NBCDs, bioequivalence, and clinical safety. The scope includes an evaluation of marketed generic formulations, their regulatory registrations, and published comparative studies. We also discuss the clinical consequences of administering unstable generics during high-dose protocols. While recognizing the urgent need for affordable generic alternatives to democratize access in low- and middle-income countries (LMICs), we emphasize the necessity for stringent, internationally harmonized regulatory standards beyond conventional bioequivalence. Safeguarding biopharmaceutical fidelity is an indispensable clinical imperative to protect vulnerable patients from the severe hidden costs of therapeutic failure and drug-induced toxicity.

As the largest and most externally exposed organ, the skin is particularly vulnerable to aging, rendering skin aging a widespread clinical and aesthetic concern. Driven by both intrinsic and extrinsic factors, skin aging is characterized by progressive functional decline and structural remodeling that compromise barrier integrity, disrupt dermal homeostasis, and ultimately diminish quality of life. At the upstream regulatory level, skin aging-associated epigenetic modifications drive epigenetic drift that compromises transcriptional fidelity and primes cells toward senescence. At the cellular level, regulatory mechanisms converge on cellular senescence and profound mitochondrial remodeling. At the microenvironmental level, the failure of senescent cell clearance (immunosenescence) and the emergence of a chronic pro-inflammatory milieu (inflammaging) create a self-reinforcing immune-inflammatory axis. This axis exacerbates cytokine production, extracellular matrix remodeling, and progressive tissue degeneration. We further highlight emerging mechanism-targeted interventions, including epigenetic and mitochondrial modulators, senotherapeutics, biologics, immunotherapies, regenerative and device-based therapies. A deeper understanding of these interconnected molecular mechanisms and targeted therapies may offer a roadmap for future therapeutic innovation and translational research in skin aging.

Aging is a multifactorial process driven by interconnected hallmarks, including chronic inflammation, mitochondrial dysfunction, genomic and epigenetic alterations, and dysregulated intercellular communication. Extracellular vesicles (EVs), naturally derived nanoscale membrane vesicles capable of transporting diverse bioactive cargoes across tissues and biological barriers, have emerged as a highly promising platform for regenerative and anti-aging therapeutics. In this review, we systematically summarize the multifaceted anti-aging mechanisms of EVs, including suppression of the senescence-associated secretory phenotype (SASP), remodeling of the immune microenvironment, mitochondrial restoration and metabolic reprogramming, DNA damage repair, epigenetic modulation, recovery of proteostasis, activation of regenerative signaling pathways, and cross-organ communication-mediated rejuvenation. Beyond mechanistic insights, we integrate the targeting biology and cellular entry properties of EVs, encompassing natural tropism determinants, engineered targeting strategies, biodistribution profiles, receptor-ligand interactions, intracellular trafficking, and subcellular cargo release. Unlike previous reviews focusing on a single EV source or isolated pathways, we establish a comprehensive framework connecting molecular mechanisms with delivery engineering, tissue targeting, biosafety assessment, scalable manufacturing, and clinical translation. We address major technical bottlenecks limiting EV therapeutics-including EV heterogeneity, suboptimal delivery efficiency, endosomal degradation, and the lack of standardized quality-control frameworks-while highlighting emerging solutions such as bioengineered EVs, hybrid vesicle platforms, biomaterial-assisted delivery systems, and ultrasound-enhanced targeting technologies. By bridging fundamental biology, nanomedicine engineering, and clinical translation, this review provides a strategic roadmap for the development of next-generation precision anti-aging nanotherapeutics with systemic regulatory capacity, translational feasibility, and broad clinical potential.

Background: Myocardial infarction triggers a complex remodeling process involving inflammation, hypertrophy, fibrosis, and electrical adaptation, ultimately predisposing the heart to failure. Krüppel-like factors (KLFs) are transcriptional regulators implicated in cardiovascular development and disease; however, a comprehensive temporal characterization of their coordinated activity during post-injury remodeling remains lacking. Objective: To define the temporal orchestration of the KLF family during myocardial injury and hypertrophy, and to integrate these dynamics within regulatory networks associated with cardiac remodeling. Methods: Myocardial injury was induced in rats using intraperitoneal isoproterenol. Left ventricular tissue was collected over a 21-day period. Cardiac morphometry, histology, immunohistochemistry, and quantitative gene expression analyses were performed to evaluate structural and transcriptional changes. Publicly available human cardiac and fibroblast datasets were analyzed for translational comparison, and protein-protein interaction networks were constructed to identify functional associations. Results: Isoproterenol treatment induced progressive hypertrophy, structural disorganization, and sustained fibrotic remodeling. KLFs displayed coordinated, phase-specific regulation, characterized by early activation of inflammation-associated members, intermediate engagement of factors linked to transforming growth factor signaling and hypertrophy modulation, and late induction of regulators associated with apoptosis and scar formation. These temporal patterns paralleled changes in inflammatory mediators, cardiac transcription factors, and genes involved in electrical and calcium handling pathways. Human expression analyses supported tissue-specific specialization of key KLFs. Conclusions: KLFs exhibit a coordinated and temporally structured regulatory program during myocardial remodeling, functioning as a transcriptional network that integrates inflammation, fibrosis, hypertrophy, and electrical adaptation. These findings position KLFs as key regulatory nodes in cardiac remodeling and potential targets for therapeutic intervention.

Artificial intelligence (AI) is transforming drug discovery and development, fields historically constrained by long timelines, high costs, and substantial attrition. Recent advances, particularly in generative modeling, enable an accelerated and increasingly systematic exploration of vast chemical and biological spaces, improving molecular interaction modeling and streamlining the identification and optimization of therapeutic candidates. However, the true utility of this expanded search space remains strictly bounded by the quality of upstream data and the logistical constraints of downstream experimental validation. Emerging platforms, including scaffold-aware and 3D molecular design tools (e.g., AlphaFold, MoleR, and PocketCrafter), single-cell foundation models, and large language models (LLMs), are expanding AI's applicability across the research and development pipeline, spanning target identification, drug discovery, lead optimization, phenotypic screening, and precision biology.AI is also increasingly integrated into preclinical and clinical research workflows, informing adaptive trial design, enabling AI-driven drug repurposing, and supporting the development of safer and more personalized therapies. While the U.S. FDA has approved numerous AI-enabled medical devices and software tools, no fully AI-discovered and AI-designed drug has yet received marketing approval. Nonetheless, several AI-originated candidates have progressed into clinical development, underscoring AI's growing translational impact. Collectively, these advances position AI as a collaborative "lab partner," capable of uncovering non-intuitive molecular designs, accelerating target and lead optimization, and enabling exploration of previously inaccessible chemical and biological space to inform downstream development and clinical decision-making. Despite gains in efficiency, scalability, and cost reduction, the broader impact of AI depends on access to high-quality multimodal data, robust regulatory and ethical frameworks, and careful recognition of methodological limitations. This review critically examines the evolution of AI approaches, highlighting key challenges and opportunities that shape the future of data-driven therapeutic innovation.

The field of oncology has witnessed remarkable progress with the integration of high-tech innovations in tumor ablation. Tumor ablation therapies, such as radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (Cryo), irreversible electroporation (IRE), and electrochemotherapy (ECT) have evolved beyond conventional boundaries, offering patients less invasive, highly targeted therapeutic options. Since it works across cancer histologies, tumor ablation is being integrated into cancer care at several levels. Tumor ablation is even considered curative in selected patients with small primary or secondary tumors, e.g. in the liver. Furthermore, it is central in treatment of oligometastatic disease or oligoprogression. Finally, ablation is widely used for symptomatic relief when tumors lead to symptoms affecting quality of life. Knowledge about ablative therapies and their inclusion at multidisciplinary team decision making enables effective and more personalized treatment for patients. This review synthesizes emerging applications of these therapies, focusing on artificial intelligence-driven personalization, robotic-assisted precision, and hybrid models combining ablation with systemic treatments, immunotherapy or targeted drug delivery. It also discusses the infrastructural, educational, regulatory, and ethical challenges that influence the clinical adoption of such treatments. Finally, the review presents strategic recommendations for integrating advanced ablation therapies into healthcare systems while ensuring equity, patient trust, and global accessibility.

Early in the pathogenesis of pulmonary fibrosis (PF), there are multiple inflammatory cell infiltrations in the damaged lung tissue. When lung injury persists, inflammatory cytokines prompt local fibroblasts migration and hyperproliferation, triggering abnormal deposition of extracellular matrix in the lung interstitium. This excessive repair leads to interstitial cell reorganization, triggering lung tissue fibrosis and further activation of inflammatory cells. Therefore, modulation of inflammatory mediators is of great significance in the treatment and prevention in the process of fibrosis. Cortex Mori Radicis (CMR) is a traditional Chinese herb with anti-inflammatory and antifibrotic properties. In this study, we investigated the therapeutic effects of CMR on bleomycin-induced PF using in vivo and in vitro models. In vivo experiments showed that CMR treatment significantly reduced inflammation, attenuated fibrosis, and alleviated lung function decline. In vitro, CMR inhibited migration, proliferation, and epithelial-mesenchymal transition (EMT) in A549 lung epithelial cells. Network pharmacological analysis identified 25 bioactive components and 10 key therapeutic targets in CMR, with the PI3K/AKT signaling pathway emerging as the core regulatory mechanism. Subsequent in vivo validation confirmed that CMR could inhibit the activation of the PI3K/AKT pathway. In conclusion, CMR exerts protective effects against PF by modulating the PI3K/AKT pathway, thereby attenuating inflammation and fibrotic remodeling. This study provides both pharmacodynamic evidence and mechanistic insight supporting the clinical potential of CMR and underscores the advantages of multitargeted intervention strategies offered by traditional Chinese medicine in the treatment of PF.

TGR5 and FXR are key regulators of metabolic homeostasis and cardiovascular health. Since the cardioprotective capacity of TGR5 activation and FXR inhibition has been recognized, dual modulation of these targets offers a promising therapeutic strategy for myocardial ischemia/reperfusion injury. Herein, sulfonyl benzoic acid derivatives were identified as effective bidirectional modulators, with compound E6 emerging as a potent lead compound. E6 demonstrated robust dual-target activity, significantly preserving cardiomyocyte viability and attenuated reactive oxygen specie overproduction in hypoxia/reoxygenation models. Moreover, oral administration of E6 markedly reduced infarct size and improved cardiac contractile function after ischemia/reperfusion in vivo, without inducing gallbladder-related side effects. Notably, E6 demonstrated superior efficacy in restoring systolic function compared to mono-regulators. Transcriptomic analysis and subsequent validation studies suggested that its therapeutic effects are mediated through favorable modulation of inflammatory response, attenuation of apoptosis, and enhanced cardiomyocytes survival. Our findings underscore the therapeutic advantages of dual TGR5/FXR targeting and establish E6 as a promising bifunctional lead compound for the treatment of myocardial ischemia/reperfusion injury.