Adeline Yoke Yin Chia

Diabetes mellitus is characterised by progressive loss or dysfunction of functional β-cell mass arising through distinct but overlapping mechanisms in type 1 and type 2 diabetes, including autoimmune-mediated destruction, metabolic stress, and microenvironmental dysfunction. Despite major advances in pharmacological and technological management, current therapies remain largely compensatory and have not consistently restored endogenous β-cell function. Stem cell–based approaches have therefore emerged as promising strategies to address the underlying pathophysiology of the disease. This review synthesises stem cell–based therapies across four complementary therapeutic components: (1) β-cell replacement through pluripotent stem cell differentiation and emerging platforms such as direct reprogramming and islet organoids; (2) systemic immune modulation or immune resetting via hematopoietic stem cell–based interventions and regulatory immune modulation; (3) local graft protection and microenvironmental repair mediated by mesenchymal stromal cells, extracellular vesicles, and biomaterial-based approaches; and (4) cell-intrinsic immune engineering to reduce immune recognition of transplanted cells. While β-cell replacement strategies have demonstrated significant progress toward generating functional insulin-producing cells, their clinical efficacy remains constrained by incomplete maturation, immune rejection, and limited engraftment. Immune resetting approaches provide mechanistic evidence for the potential reversibility of autoimmune dysfunction but are limited by toxicity and the lack of durable tolerance. In contrast, local paracrine and microenvironmental strategies exert immunomodulatory and cytoprotective effects that stabilise the islet microenvironment but do not directly restore β-cell mass. Cell-intrinsic immune engineering offers an alternative strategy to reduce immune recognition of transplanted cells, although long-term immune evasion, genomic safety, and graft durability remain important translational challenges. These findings indicate that single-modality approaches are unlikely to be sufficient to achieve durable disease modification. Instead, effective therapeutic strategies may require integrated, multi-axis interventions that combine β-cell replacement, immune modulation, and microenvironmental support. Emerging advances in genome engineering, biomaterial-based encapsulation, and extracellular vesicle engineering are likely to facilitate this transition toward coordinated regenerative therapies. This integrated framework provides a systems-level perspective on current limitations and future directions for stem cell-based treatment of diabetes mellitus.

Acinetobacter baumannii é um patógeno nosocomial crítico cuja persistência está intimamente ligada à sobrevivência associada ao biofilme. Esta revisão narrativa examinou criticamente determinantes estruturais, redes regulatórias, força das evidências e pontos de intervenção ao longo do ciclo de vida do biofilme. Buscas direcionadas e reprodutíveis no PubMed, Scopus e Web of Science não utilizaram limite inferior de data e foram conduzidas pela última vez em abril de 2026, priorizando evidências mecanísticas, estruturais, de isolados clínicos e in vivo. A literatura apoia uma rede dependente do contexto na qual as fímbrias Csu, Ata e OmpA interagem com BfmRS, quorum sensing, di-GMP cíclico, LeuO e sistemas de exportação da matriz. A revisão distingue a resistência antimicrobiana herdada geneticamente da tolerância e persistência reversíveis associadas ao biofilme, identifica controvérsias dependentes da cepa e do modelo, e mapeia estratégias antiadesão, de sinalização, da matriz, fágicas e antipersistência. Como a maioria das intervenções permanece pré-clínica, o controle do biofilme pode se beneficiar de combinações específicas de estágio cuja penetração, toxicidade, estabilidade e risco de resistência sejam avaliados em modelos clinicamente relevantes.

Acinetobacter baumannii is a critical nosocomial pathogen whose persistence is closely linked to biofilm-associated survival. This narrative review critically examined structural determinants, regulatory networks, evidence strength, and intervention points across the biofilm lifecycle. Reproducible targeted searches of PubMed, Scopus, and Web of Science used no lower date limit and were last conducted in April 2026, prioritizing mechanistic, structural, clinical-isolate, and in vivo evidence. The literature supports a context-dependent network in which Csu pili, Ata, and OmpA interact with BfmRS, quorum sensing, cyclic di-GMP, LeuO, and matrix-export systems. The review distinguishes genetically inherited antimicrobial resistance from reversible biofilm-associated tolerance and persistence, identifies strain- and model-dependent controversies, and maps anti-adhesion, signaling, matrix, phage, and anti-persister strategies. Because most interventions remain preclinical, biofilm control may benefit from stage-specific combinations whose penetration, toxicity, stability, and resistance risk are evaluated in clinically relevant models.

Background: Cordyceps militaris (C. militaris) is a medicinal mushroom recognized for its diverse pharmacological activities, largely attributed to its principal bioactive nucleosides, cordycepin and adenosine. Although accumulating evidence supports their neuroprotective potential, the molecular mechanisms underlying their effects against Alzheimer’s disease (AD) remain incompletely understood. This study investigated the neuroprotective effects of cordycepin and adenosine against amyloid-β (Aβ₄₂)-induced neurotoxicity and explored their potential molecular mechanisms using integrated experimental and computational approaches. Methods: SH-SY5Y neuroblastoma cells were pretreated with cordycepin (COR), adenosine (ADE), or donepezil (DNPZ) prior to Aβ₄₂ exposure, and cell viability was assessed using the MTT assay. Drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were evaluated in silico, followed by network pharmacology to identify potential therapeutic targets and enriched biological pathways. Molecular docking and molecular dynamics simulations were performed to elucidate the interactions of the compounds with selected Alzheimer’s disease-related proteins. Results: COR and ADE significantly attenuated Aβ₄₂-induced cytotoxicity and improved SH-SY5Y cell viability. Network pharmacology identified 84 shared molecular targets, including 9 AD-associated genes. Protein–protein interaction analysis revealed hub genes involved in signal transduction, epigenetic regulation, and purine metabolism, while Gene Ontology and KEGG enrichment analyses highlighted pathways associated with neuroactive ligand–receptor interaction, calcium signaling, and inflammatory regulation. ADMET analysis predicted favorable pharmacokinetic properties for both compounds, although cordycepin was predicted to be AMES-positive. Molecular docking and molecular dynamics simulations demonstrated stable interactions of COR and ADE with liver X receptors (LXRα and LXRβ), whereas donepezil exhibited stronger binding affinity toward β-secretase (BACE1). Conclusions: COR and ADE exert neuroprotective effects through coordinated modulation of multiple AD-related signaling pathways rather than a single molecular target. These findings provide mechanistic insights into the neuroprotective activities of C. militaris-derived nucleosides and support further investigation of their potential as multi-target therapeutic candidates for AD and other neurodegenerative disorders.

Introduction. Cordyceps militaris (CM), a traditional medicinal fungus in East Asia, has attracted increasing attention for its anticancer potential. Despite extensive use in traditional medicine, the mechanisms underlying its antimetastatic and antiangiogenic effects in breast cancer remain unclear. This study aimed to explore the bioactive components of aqueous extracts derived from CM’s mycelium (Aq-CMM) and fruiting body (Aq-CMF), focusing on their potential inhibitory activities on metastasis and angiogenesis in triple-negative breast cancer cells (MDA-MB-231). Materials and methods. In silico molecular docking was conducted to screen for key CM bioactive compounds and evaluate their binding affinities toward metastasis- and angiogenesis-related targets, NF-κB and VEGFR. In vitro cytotoxicity was assessed using 2D monolayer and 3D spheroid MDA-MB-231 cultures treated with Aq-CMM and Aq-CMF. Cell viability (IC₅₀) was determined at 48 hours, and microscopic evaluation of treated spheroids was performed to assess morphological disruption. Results and conclusions. Docking analyses identified ergothioneine as a major CM-derived compound with strong binding affinity to NF-κB (−7.83 kcal/mol) and VEGFR (−7.62 kcal/mol), suggesting potent inhibitory effects on metastatic and angiogenic pathways. In vitro assays showed that Aq-CMF exerted greater growth-inhibitory effects (IC₅₀ = 54 µg/mL in 2D; 46 µg/mL in 3D) than Aq-CMM at 48 hours. Microscopic observations confirmed notable disruption of spheroid architecture following treatment. These findings highlight the therapeutic potential of ergothioneine-rich CM extracts, particularly from the fruiting body, as promising anticancer agents that warrant further mechanistic and translational studies.

Diabetes mellitus, encompassing both T1DM and T2DM, represents a global health challenge. While traditional therapies focus on managing symptoms, emerging stem cell therapies, particularly MSCs, offer potential curative approaches. This review explores advancements in diabetes research with an emphasis on mesenchymal stem cells (MSCs). Additionally, we discuss clinical trials and applications of MSCs in diabetes treatment, providing a comprehensive analysis of this promising therapeutic frontier. MSCs have been shown to provide immunomodulatory effects, delay disease progression and reverse insulin resistance in preclinical and clinical studies. MSC-derived EVs have been extensively studied as well, exhibiting similar therapeutic benefits while also possibly having lower immunogenicity than MSCs. Phase I and II clinical studies have demonstrated MSCs to be effective in juvenile T1DM and able to significantly reduce HbA1c, fasting blood glucose, insulin demand and plasma blood glucose levels (p < 0.05). There is however a lack of standardisation of protocols across studies, highlighting the need for comparative studies to establish the optimal dosing, treatment schedule, administration route and source of MSCs. Large-scale randomised controlled trials are necessary to establish safety and efficacy in human patients, paving the way for MSC-based therapies in diabetes treatment. Clinical trial number: Not applicable.

The theme "Beyond the Framework: Leaping between Disciplines" addresses the growing importance of cross-disciplinary research, particularly in Life Sciences, Medicine, and Biomedicine. This Special Issue, explores how research that transcends traditional disciplinary boundaries can lead to breakthroughs in complex health challenges. The convergence of these fields fosters innovation by integrating diverse methodologies, perspectives, and technologies. This Special Issue highlights the value of interdisciplinary approaches in advancing understanding of diseases, developing novel treatments, and improving patient outcomes. Our contributors delve into a wide range of topics, including regenerative medicine, personalized healthcare, and biomaterials, showcasing collaborative research that has led to significant advancements. By breaking down silos, researchers from these domains can create more holistic solutions to pressing health concerns such as cancer, neurodegenerative disorders, and metabolic diseases. This issue aims to inspire researchers and clinicians to pursue collaborative projects that transcend traditional boundaries, fostering innovation and promoting sustainable healthcare solutions.

: Natural products have long garnered the interest of scientific communities as they have proven to be an effective therapeutic resource that paved the path for medicinal research and drug development. Among them, Cordyceps militaris is an entomopathogenic caterpillar fungus with a renowned history of being utilized as a medicinal remedy for centuries in Eastern civilizations. The number of pharmacological functions reported by this specific fungus resulted in continuous efforts to unravel new effective bioactive compounds and their corresponding mechanism of action. As time progresses, computational techniques become the forefront of genomic and proteomic analysis, besides acting as a platform for integrating various up-to-date multidisciplinary data sources. This review briefly introduces Cordyceps militaris alongside the latest known biologically active compounds and their respective therapeutic potential. The need to implement computational applications to cope with the continuous phytochemical evolution of Cordyceps militaris will be illustrated. Moreover, many databases, mathematical algorithms, or sourcing tools that could benefit data visualization, dissemination, and interpretation aligned to fungal-based research are enumerated, in addition to describing some of the broad discoveries relative to Cordyceps militaris in the past. In conclusion, using advanced computational technology may be the foundation to leverage natural product discovery about Cordyceps militaris and contribute to future mass production of this fungus for commercial purposes in the world pharmaceutical industry.

Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.