Search Results (143)

Non-tuberculous mycobacteria (NTM) comprise more than 190 species capable of causing severe pulmonary, lymphatic, cutaneous, and disseminated infections, particularly in immunocompromised populations. Over the past two decades, the global incidence of NTM infections has risen steadily, underscoring an urgent unmet medical need. Treatment remains highly challenging due to intrinsic antimicrobial resistance and the requirement for prolonged multidrug regimens that are often poorly tolerated and associated with unsatisfactory outcomes. At the same time, the development of novel therapies has lagged behind other disease areas, hindered by the high costs of antimicrobial drug discovery and the relatively low commercial return compared with treatments for chronic conditions. Over the past decade, discovery and development have diversified across novel small molecules, next-generation analogues of existing classes, and adjunctive or host-directed strategies. While most candidates remain preclinical, several agents have advanced clinically in other infections, including gepotidacin (topoisomerase inhibitor; FDA-approved 2025 for urinary tract infection (UTI)), sulbactam–durlobactam (DBO β-lactamase inhibitor; FDA-approved 2023 for Acinetobacter baumannii complex), and contezolid, supporting repurposing opportunities for NTM. Conversely, SPR720 (gyrase B prodrug) was suspended after not meeting its Phase 2 endpoint in 2024, underscoring translational risk. Overall, the NTM pipeline is expanding, with near-term progress most likely from repurposed agents and optimised combinations, alongside earlier-stage candidates that target biofilms or resistance mechanisms. This review aims to provide a critical and up-to-date overview of emerging antimicrobial strategies against NTM, highlighting recent advances, translational challenges, and opportunities to accelerate the development of effective therapeutics. Full article

Precision oncology is broadly defined as cancer prevention, diagnosis, and treatment specifically tailored to the patient based on his/her genetics and molecular profile. In simple terms, the goal of precision medicine is to deliver the right cancer treatment to the right patient, at the right dose, at the right time. Precision oncology is the most studied and widely applied subarea of precision medicine. Now, precision oncology has expanded to include modern technology (big data, single-cell spatial multiomics, molecular imaging, liquid biopsy, CRISPR gene editing, stem cells, organoids), a deeper understanding of cancer biology (driver cancer genes, single nucleotide polymorphism, cancer initiation, intratumor heterogeneity, tumor microenvironment ecosystem, pan-cancer), cancer stratification (subtyping of traditionally defined cancer types and pan-cancer re-classification based on shared properties across traditionally defined cancer types), clinical applications (cancer prevention, early detection, diagnosis, targeted therapy, minimal residual disease monitoring, managing drug resistance), lifestyle changes (physical activity, smoking, alcohol consumption, sunscreen), cost management, public policy, and more. Despite being the most developed area in precision medicine, precision oncology is still in its early stages and faces multiple challenges that need to be overcome for its successful implementation. In this review, we examine the history, development, and future directions of precision oncology by focusing on emerging technology, novel concepts and principles, molecular cancer stratification, and clinical applications. Full article

Bio-gels are a class of functional polymeric materials with three-dimensional network structures. Their exceptional biocompatibility, biodegradability, high specific surface area, and tunable physicochemical properties make them highly promising for environmental remediation. This article systematically reviews the classification of bio-gels based on source, cross-linking mechanisms, and functional attributes. It also elaborates on their fundamental properties such as porous structure, high water absorbency, stimuli-responsiveness, and mechanical stability and examines how these properties influence their environmental remediation efficiency. This review comprehensively analyze the mechanisms and efficacy of bio-gels in adsorbing heavy metal ions, removing organic dyes, improving soil water retention, and restoring ecosystems. Special attention is given to the interactions between surface functional groups and contaminants, the role of porous structures in mass transfer, and the ecological effects within soil–plant systems. Additionally, this review explores extended applications of bio-gels in medical tissue engineering, controlled release of drugs and fertilizers, and enhanced oil recovery, highlighting their versatility as multifunctional materials. Finally, based on current progress and challenges, this review outline key future research directions. These include elucidating microscopic interaction mechanisms, developing low-cost renewable feedstocks, designing multi-stimuli-responsive structures, improving long-term stability, and establishing full life-cycle environmental safety assessments. These efforts will help advance the efficient, precise, and sustainable use of bio-gels in environmental remediation, offering innovative solutions to complex environmental problems. Full article

Monkeypox (Mpox) has re-emerged as a global public health threat, with recent outbreaks linked to novel mutations that enhance viral transmissibility and immune evasion. The Mpox virus (MPXV), a double-stranded deoxyribonucleic acid (DNA) orthopoxvirus, shares high structural and enzymatic similarity with the variola virus, underscoring the need for urgent therapeutic interventions. While conventional antiviral development is time-intensive and costly, drug repurposing offers a rapid and cost-effective strategy by leveraging the established safety and pharmacological profiles of existing medications. This is a narrative integrative review synthesizing published evidence on drug repurposing strategies against MPXV. To address these issues, this review explores MPXV molecular targets critical for genome replication, transcription, and viral assembly, highlighting how the Food and Drug Administration (FDA)-approved antivirals (cidofovir, tecovirimat), antibiotics (minocycline, nitroxoline), antimalarials (atovaquone, mefloquine), immunomodulators (infliximab, adalimumab), and chemotherapeutics (doxorubicin) have demonstrated inhibitory activity against the virus using computational or experimental approaches. This review further evaluates advances in computational methodologies that have accelerated the identification of host-directed and viral-directed therapeutic candidates. Nonetheless, translational challenges persist, including pharmacokinetic limitations, toxicity concerns, and the limited efficacy of current antivirals such as tecovirimat in severe Mpox cases. Future research should integrate computational predictions with high-throughput screening, organ-on-chip technologies, and clinical pipelines, while using real-time genomic surveillance to track viral evolution. These strategies establish a scalable and sustainable framework for the MPXV drug discovery. Full article

Objective: This study evaluated the cost-effectiveness of sacituzumab govitecan (SG) compared with single-agent chemotherapy of the physician’s choice (TPC) from the perspective of Taiwan’s National Health Insurance. Methods: A partitioned survival model was developed to assess outcomes in patients with metastatic triple-negative breast cancer (mTNBC). Clinical data were derived from the ASCENT trial, while direct medical costs were obtained from Taiwan’s National Health Insurance Administration (NHIA). Utility values were taken from published literature. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to examine parameter uncertainty and test the robustness of the results. Results: In the base-case analysis, SG was associated with an incremental cost of USD 121,836 per QALY gained—exceeding Taiwan’s willingness-to-pay (WTP) threshold of USD 102,120. One-way sensitivity analyses indicated that SG drug cost was the primary driver of ICER variability. Probabilistic sensitivity analysis showed that reducing the price of SG by 50% increased the likelihood of cost-effectiveness. Conclusions: From the NHIA perspective, SG is not cost-effective for patients with advanced or metastatic TNBC at its current price. Substantial price reductions would be required for SG to become cost-effective under the WTP threshold of USD 102,120 per QALY. Full article

The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article

Background: Prostate cancer is the second most common malignant cancer among men, and according to the predictions, the estimated number of new cases will substantially grow in the coming years. Therefore, the costs of the disease will increase as well. Methods: We conducted a literature review of the state of knowledge about the costs of treatment and the economic burden of prostate cancer. The vast majority of studies were focused on direct costs only, which clearly shows the literature gap. Results: We focused on the estimates of direct costs, i.e., treatment of prostate cancer, adjuvant and neoadjuvant treatment, and supportive and palliative care, and indirect costs. Cost-effectiveness analyses indicated that docetaxel combined with androgen deprivation therapy (ADT) was the most cost-effective strategy for metastatic hormone-sensitive prostate cancer (incremental cost-effectiveness ratio (ICER): USD 13,647). In contrast, novel therapies such as PARP inhibitors and whole-genome-sequencing-guided treatments were not cost-effective unless drug prices were reduced by 47–70%. In the United States, 5-year cumulative treatment costs ranged from USD 48,000 for conservative management to over USD 91,000 for radiotherapy, while out-of-pocket expenses averaged AUD 1172 in Australia. Indirect costs were also considerable, with Slovakia reporting an increase in sick leave costs from EUR 1.2 million in 2014 to EUR 2.1 million in 2022. Conclusions: Metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer were the most frequent categories for various treatment cost evaluations. A few specific combinations of drugs were cost-effective only under the condition of dropping the unit prices of a medication. Further summarizing, reviewing, and developing a methodology for standardized comparisons are needed. Full article

Biological drugs have revolutionized the treatment of many chronic diseases, starting with cancer. They normally consist of antibodies that are also effectively used to treat several autoimmune diseases, including psoriasis. These products, called biologics, work by selectively blocking the activity of certain targets, mainly cytokines, which play a crucial role in the pathogenic and inflammatory processes involved in a particular disease. Unfortunately, a reduction in response to these biological treatments may occur over time, and this phenomenon is often due to the development of antibodies against the therapeutic antibodies. The immune responses directed to these therapeutics range from transient anti-drug antibodies (ADA) formation, with no clinical significance, to the generation of high titers and persistence of ADA, causing loss of efficacy. Considering the costs associated with the use of biological drugs, there is growing interest in identifying biomarkers that can predict clinical response to personalize treatments. Full article

Background/Objectives: Dyslipidemia is becoming a significant economic healthcare burden in low- to middle-income countries (LMICs) due to its role in heightening cardiovascular-related mortality. Statins are the first-line treatment for reducing LDL-C levels, thereby minimizing direct costs associated with cardiovascular disease management, with pitavastatin being of the newest generation of statins. This research work conducted a cost-utility analysis of pitavastatin to determine the economic benefit in Vietnam. Methods: A decision tree model was developed to compare the rate of LDL-C controlled patients over a lifetime horizon among patients treated with pitavastatin, atorvastatin, and rosuvastatin. The primary outcome was the incremental cost-effectiveness ratio (ICER), measured from the healthcare system perspective. Effectiveness was evaluated in terms of quality-adjusted life years (QALYs), using an annual discount rate of 3%. A one-way sensitivity analysis was performed to identify the key input parameters that most influenced the ICER outcomes. Results: Pitavastatin was cost-effective compared to atorvastatin but was dominated by rosuvastatin. Although pitavastatin gained fewer QALYs than atorvastatin, the ICER was 195,403,312 VND/QALY, well below Vietnam’s 2024 willingness-to-pay. Drug cost had the most significant impact on ICERs. Conclusions: Pitavastatin represents an economical short-term alternative to atorvastatin, particularly in resource-constrained settings. Full article

The global escalation of antimicrobial resistance (AMR) among Gram-negative bacteria poses a severe threat to public health. Traditional antibiotic development struggles to keep pace with emerging resistant strains, necessitating innovative strategies to enhance therapeutic options. This review explores the potential of drug repurposing as a strategic approach to combat Gram-negative bacterial infections, focusing on clinically approved drugs with antibacterial properties or the capacity to enhance antibiotic efficacy through direct or host-directed mechanisms. Within the review, a special section is dedicated to the potential usage of repurposed drugs against bacteria that can be used as biological warfare agents, exposure to which may lead to mass casualties, in particular if these pathogens are resistant to antibiotics. Repurposed drugs exhibit diverse antibacterial mechanisms, including membrane disruption, efflux pump inhibition, iron metabolism interference, quorum sensing suppression, and biofilm inhibition. Additionally, many agents demonstrated host-directed therapeutic effects by modulating inflammatory responses, enhancing autophagy, or boosting innate immune functions. Drug repurposing offers a promising avenue to mitigate the AMR crisis by providing rapid, cost-effective therapeutic solutions. Combining repurposed drugs with existing antibiotics or employing them as host-directed therapies holds significant potential for treating infections caused by multidrug-resistant Gram-negative pathogens. Continued research and clinical validation are essential to translate these findings into effective treatment regimens. Full article

Deuterium-labelled amino acids have found extensive applications in such research areas as pharmaceutical, bioanalytical, neutron diffraction, inelastic neutron scattering, in analysis of drug metabolism using mass spectrometry (MS), and, structuring of biomolecules by NMR. For these reasons, interest in new methodologies for the deuterium labelling of amino acids and the extent of their applications are equally rising. The ideal method will be able to label target compounds rapidly and cost-effectively by the direct exchange of a hydrogen atom by a deuterium atom. Most of these exchange reactions can often be carried out directly on the final target compound or a late intermediate in the synthesis, and often D₂O can be used as the deuterium source. This review aims to provide a high-level overview of the chemical deuteration of amino acids in various groups (aromatic, heterocyclic, and non-aromatic α-amino acids). It primarily focuses on metal-catalyzed H/D exchange under hydrothermal conditions, with some attention given to studies on stereoselectivity and chemically synthesized perdeuteration and selective deuteration. In addition, we present different methods tested, manipulated, and developed for versatile new scalable protocols for preparation of selective and perdeuterated biologically important amino acids and their enzymatic and kinetic resolution to give pure enantiomers. Different methods for the synthesis of stereocontrolled selective and perdeuterated amino acids, including synthetic, and methods for preparing optically pure amino acids are presented. Full article

Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article

Crystal twinning, a common growth phenomenon, can substantially affect material performance in fields such as semiconductors, nonlinear optics, and drug development, yet its elimination during crystallization is challenging. This study presents a method for the controlled synthesis of ZSM-5 zeolite as either single crystals or twinned crystals using kaolin as the primary raw material. The method leverages the etching effect of ammonium fluoride (NH${⁠}_4$F) on the aluminosilicate structure derived from pre-treated kaolin. By adjusting the concentrations of NH${⁠}_4$F and the structure-directing agent tetrapropylammonium bromide (TPABr), pure ZSM-5 single crystals and twinned crystals were selectively synthesized. Conventionally, NH${⁠}_4$F is employed to introduce defects into zeolite structures. In contrast, this work demonstrates its utility in controlling crystal habit. The synthesis utilizes kaolin, an abundant and low-cost aluminosilicate mineral, to provide the entire aluminum source and a portion of the silicon source, offering an economical alternative to expensive precursors like aluminum isopropoxide. The resulting single and twinned crystals exhibited high crystallinity, demonstrating the viability of using natural minerals to produce high-quality zeolites. The physical and chemical properties of the kaolin-derived ZSM-5 were characterized and compared to those of ZSM-5 synthesized from conventional chemical reagents. A growth mechanism for the formation of single and twinned crystals is also proposed. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Healthcare data rapidly increases, and patients seek customized, effective healthcare services. Big data and machine learning (ML) enabled smart healthcare systems hold revolutionary potential. Unlike previous reviews that separately address AI or big data, this work synthesizes their convergence through real-world case studies, cross-domain ML applications, and a critical discussion on ethical integration in smart diagnostics. The review focuses on the role of big data analysis and ML towards better diagnosis, improved efficiency of operations, and individualized care for patients. It explores the principal challenges of data heterogeneity, privacy, computational complexity, and advanced methods such as federated learning (FL) and edge computing. Applications in real-world settings, such as disease prediction, medical imaging, drug discovery, and remote monitoring, illustrate how ML methods, such as deep learning (DL) and natural language processing (NLP), enhance clinical decision-making. A comparison of ML models highlights their value in dealing with large and heterogeneous healthcare datasets. In addition, the use of nascent technologies such as wearables and Internet of Medical Things (IoMT) is examined for their role in supporting real-time data-driven delivery of healthcare. The paper emphasizes the pragmatic application of intelligent systems by highlighting case studies that reflect up to 95% diagnostic accuracy and cost savings. The review ends with future directions that seek to develop scalable, ethical, and interpretable AI-powered healthcare systems. It bridges the gap between ML algorithms and smart diagnostics, offering critical perspectives for clinicians, data scientists, and policymakers. Full article