Organoids, which recapitulate human organ structure and function, have been widely used in disease modeling, drug discovery, personalized medicine, and regenerative therapy, demonstrating strong potential for future biomedical applications. Successful organoid culture (OC) depends on a matrix that provides mechanical support and in vivo microenvironment mimicry, both essential for cellular adhesion, proliferation, and differentiation. Owing to their tunable stiffness and viscoelasticity, which enable adaptation to diverse OCs, hydrogels have become key materials in OC matrix development. This review summarizes current advances in hydrogel systems, encompassing naturally derived and synthetic hydrogels used in OC, with an emphasis on their composition and physicochemical properties. This study aims to provide guidance for hydrogel selection in organoid research. This study further explores how hydrogel composition governs gelation behavior and ultimately influences organoid growth and functionality, providing insights for the future engineering of u201Call-purposeu201D hydrogel matrices.
The human gut microbiome (HGM) is a complex, highly diverse microbial ecosystem with extensive enzymatic and metabolic capacity. The HGM plays a pivotal role in drug biotransformation, thereby modulating the therapeutic efficacy and pharmacokinetic profiles. Considerable interindividual variability in gut microbiota composition can produce differential metabolic activity, resulting in variable therapeutic responses to the same drug across individuals. In contrast, orally administered drugs can also affect HGM diversity and composition, impacting host health. Despite its importance, the systematic investigation of drugu2013microbiome interactions (DMIs) presents substantial experimental challenges. In recent years, machine learning (ML) has emerged as a powerful tool in biological and health sciences, offering advanced capabilities in pattern recognition and discovery of hidden relationships. This progress opens new avenues for DMI research. This review provides an overview of recent advances in HGM-mediated drug biotransformation and drug-induced HGM modification, with particular emphasis on ML applications in these areas. We aim to elucidate the critical role of ML in the systematic exploration and mechanistic understanding of DMI, highlighting its importance as a key future research direction.
Synthetic biology made the design of microbes as versatile therapeutic platforms possible, thereby transforming bacteria and synthetic microbial communities into programmable systems for health applications. This review summarizes recent progress in engineered bacterial therapeutics, emphasizing their roles in metabolic compensation, immune modulation, targeted delivery, and diagnostic sensing. Engineered strains have advanced from early proof-of-concept designs to sophisticated circuits that integrate environmental cues, respond to external stimuli, and achieve spatiotemporal control of therapeutic outputs. Similarly, synthetic microbial communities strategies provide ecological stability, functional redundancy, and customizable community interactions, offering advantages over single-strain interventions. Together, these approaches demonstrate a shift from conventional probiotics toward rationally designed microbial therapeutics that restore physiological balance and actively intervene in disease processes. Ongoing efforts address challenges, including colonization efficiency, biosafety, and regulatory adaptation, whereas emerging frameworks integrate multimodal sensing, intelligent feedback control, and clinical translation. This review emphasizes their potential to reshape future strategies for disease prevention, intervention, and personalized medicine by situating microbial therapeutics within the broader landscape of health engineering.
Colorectal cancer, as a major cause of cancer-related deaths worldwide, posing a serious challenge to human health. Conventional therapeutic strategies, including chemotherapy, radiotherapy and surgery, often suffer from inherent side effects due to the complex physiological characteristics of the intestinal environment. Accordingly, near-infrared (NIR) light-activated luminescent nanomaterials, which have recently been widely explored for colorectal cancer theranostics, offer unique advantages, such as high spatial resolution of imaging, deep penetration to tissue, and easy functionality. This review delves into recent advancements in the realm of NIR-mediated colorectal cancer nanotheranostics, underscoring the distinctive merits of these strategies. Additionally, it critically examines the existing challenges and future opportunities within this burgeoning field. By presenting a comprehensive overview of the latest developments, this review aims to equip researchers with timely and pertinent information, thereby fostering the vibrant growth and innovation of NIR-mediated nanomedicine.
Cancer stem cells (CSCs) contribute greatly to the initiation, progression, metastasis, and drug resistance of cancers. Nasopharyngeal carcinoma (NPC) is a malignant tumor that has distinct ethnic and geographical distributions and could be related to epigenetic alterations. Aberrant DNA methylation, an important type of epigenetic disorder, has long been known to be important in the pathogenesis of NPC. However, DNA methylation alterations in NPC CSCs remain unresolved. In this study, the genome-wide DNA methylation profiles of NPC cells (CNE2 and C666-1) were compared with those of their corresponding CSCs (CNE2 CSCs and C666-1 CSCs) to determine the distinct DNA methylation patterns of NPC CSCs. Compared with that of CNE2 cells, which are Epsteinu2013Barr virus (EBV)-negative NPC cells, the DNA of CNE2 CSCs is highly hypomethylated. In contrast, the DNA of EBV-harboring CSCs (C666-1 CSCs) had more hypermethylated sites than that of C666-1. The differentially methylated genes (DMGs) in CNE2 CSCs compared with those in CNE2 cells were enriched mainly in metabolism-related terms, and UGT1A9, UGT1A3, and UGT1A4 were identified as hub genes. However, the DMGs in C666-1 CSCs compared with those in C666-1 cells were enriched mainly in cancer-associated signaling pathways and virus infection-associated terms, and the hub genes were MACF1, ACTA1, and TP63. Our work revealed distinct methylation patterns in NPC CSCs, which is beneficial for obtaining a deeper understanding of the pathogenesis of NPC.
The skin is a complex organ that serves as a protective barrier and performs many other functions. Several populations of stem cells reside in the skin and are responsible for the structural and functional integrity of the organ and its behavior during skin aging. We aim to provide a comprehensive overview of current knowledge about skin stem cells and their role in aging and discuss how organoids are used in skin stem cell research, highlighting their advantages over traditional two-dimensional cell culture systems and their potential to enable us to gain more insight into aging skin and the development of regenerative therapies.
The proper storage temperature for dissolving insulin microneedles (INS MNs) is crucial for their clinical application to prevent INS inactivation. This study aimed to explore the impact of temperature on the dissolution of INS MNs and provide appropriate storage recommendations. Two commonly used materials, hyaluronic acid (HA) and polyvinyl alcohol (PVA), were selected for the fabrication of four kinds of MNs to examine the stability of these MNs with respect to molecular weight and the sucrose adjuvant: PVA MNs, PVA with sucrose MNs, and HA with molecular weights of 8 and 160 kDa MNs. The drug stability of these INS MNs was assessed at storage temperatures of 4, 25, 40, and 60u00B0C via electron microscopy, scanning electron microscopy, circular dichroism, and molecular dynamics simulations. The experimental results revealed that all four types of dissolving INS MNs remained stable for a minimum of 6 months when stored at 4u00B0C. The inclusion of sucrose has been shown to increase the structural stability of INS MNs at both 4 and 25u00B0C. Furthermore, MNs loaded with INS in a soluble form demonstrated superior stability compared with those loaded with INS solutions. On the basis of these results, tailored storage recommendations were provided for each type of dissolving INS MN. In summary, the broad storage temperature range for dissolving INS MNs not only reduces the costs associated with INS transportation and storage but also offers convenience for healthcare professionals and patients.
Background: Bipolar disorder and anxiety disorders are two prominent mental disorders that represent a significant global health challenge. Objective: The Global Burden of Disease Study 2021 (GBD 2021) was employed to evaluate sex differences in the incidence of bipolar disorder (BD) and anxiety disorder (ANX) globally by year, age, and socioeconomic status. Method: We estimated sex-specific incidence of BD and ANX from GBD 2021 globally and in 204 countries and territories from 1990 to 2021. The sociodemographic index (SDI) was used to gauge national socioeconomic development and the Health Organization (WHO) region was used as a division of regions. Differences in age-standardized incidence rates (ASRs) by sex (absolute and relative) and risk ratios (95% confidence interval) were calculated annually and by age. Annual percent change (APC) was calculated by joinpoint regression modeling and linear regression analyses were performed to explore the socioeconomic factors associated with sex differences in incidence. Results: The absolute and relative sex difference in ASRs of BD showed a slight declining trend during 1990 and 2021, with absolute difference decreasing from 2.50 to 1.83, and relative difference decreasing from 1.08 to 1.06; The absolute and relative sex difference in ASRs of ANX showed an increasing trend during 1990 and 2021, with absolute difference increasing from 170.02 to 208.08, and relative difference increasing from 1.35 to 1.36. Worldwide, females had a higher risk of BD and ANX than males in 1990and 2021. The highest Risk ratios of BD and ANX were observed in the European Region in 2021.The greatest relative sex difference of BD was 1.09 in the age group of 30-34. The greatest relative difference of ANX was 1.51 in the age group of 20-24. Relative sex differences of BD and ANX were significantly and positively correlated with SDI (BD, standardized β = 0.27 (95% CI, 0.22 to 0.33), P < 0.001; ANX, standardized β = 0.80 (95% CI, 0.47 to 1.14), P < 0.001). Conclusions: Sex difference in the incidence of anxiety disorders and bipolar disorder have persisted worldwide over the past several decades, and the rates have consistently been higher among females than males. The sex difference in the global incidence of bipolar disorder has shown a slight improvement, but that in the global incidence of anxiety disorders has not been effectively mitigated. The sex difference is even more pronounced at younger ages and in more developed nations. The findings emphasize the significance of sex-specific health policies to reduce sex differences in the incidence of bipolar and anxiety disorders. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: https://www.healthdata.org/research-analysis/gbd I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets analyzed during the current study are available from the publicly available website: https://www.healthdata.org/research-analysis/gbd.
Objective: Protein extraction methods play a crucial role in the quality, functionality, and recovery efficiency of protein products, and directly affect their subsequent applications. Hemp seeds are rich in proteins and oils, however, the process of hemp seed protein extraction has rarely been studied. To bridge this knowledge gap, we aimed to explore the effects of the extraction conditions on the yield, physicochemical characteristics, functional properties, and biological activities of hemp seed proteins. Methods: Alkaline extraction (AE), AE combined with ultrasonication (AEU), salt extraction (SE), and SE combined with ultrasonication (SEU) were used to extract the hemp seed proteins. Results: The protein yields of SE and SEU were significantly higher than those of AE and AEU. All four types of protein extracts showed no obvious differences in protein purity, which was higher than 95%, however, significant differences were observed in protein physicochemical properties, functional properties, and biological activities among the proteins obtained by the four extraction methods. The hemp seed proteins extracted by the SE (designated as HPS) and SEU (designated as HPSU) methods possessed better nutritional quality, digestion properties, higher fat absorption capacity, and a lower water-holding capacity. Moreover, we found that the proteolytic products of HPS and HPSU exhibited superior biological activities, including 2,2-diphenyl-1-picrylhydrazyl scavenging capacity and dipeptidyl-peptidase IV inhibitory activity, but similar anti-inflammatory activities. Conclusion: We concluded that SE was more suitable for the extraction of hemp seed protein because the SE method maintained the high nutritional value for the proteins. We believe that these findings contribute to a better understanding of the effects of extraction methods on protein quality.
Cancer poses a significant threat to human health because of its high morbidity and mortality. While traditional cancer therapies have demonstrated efficacy, they have limitations, such as systemic toxicity and acquired resistance. In recent years, targeting mitochondrial function has emerged as a promising approach to tumor therapy. In this review, we discuss the various methods used to specifically target mitochondria for tumor treatment and provide an overview of delivery systems designed for mitochondrial targeting in cancer therapy. By addressing the drawbacks of current treatment modalities and exploring the potential of mitochondrial targeting, this review contributes to the advancement of tumor therapy. The comprehensive analysis of the existing literature provides valuable insights and serves as a reference for researchers investigating targeted mitochondrial therapies for cancer. With a focus on novel delivery strategies, this work aims to bridge the gap between scientific exploration and clinical application, which will enhance our ability to effectively combat this pervasive health challenge.
Janus bio-adhesive hydrogels are promising for preventing postoperative tissue adhesion. However, integrating adhesive and non-adhesive interfaces involves multiple processes, posing challenges in meeting complex clinical demands. Herein, a Janus chitosan (CS) and poly(ethylene glycol) methacrylate (PEGMA) hydrogel (CS/PEG hydrogel) was developed via a one-pot phase separation polymerization process. This phase separation was driven by simultaneous hydrogelation upon ultraviolet light irradiation on the top and heating at the bottom of the precursor solution. The light-induced surface (denoted as LIS) was rich in CS, whereas the heat-induced surface (denoted as HIS) contained a large amount of PEGMA. Owing to the large amount of poly(ethylene) glycol (PEG) present, non-adhesive HIS exhibited a pore size of 235.0 u00B1 11.3 u03BCm, permitting mature vascularization. The adhesive LIS containing CS maximized the adhesiveness of the untreated wound, reaching 94.1 u00B1 3.3 Ju00B7mu22122. The three-dimensional crosslinked network ensured adequate strength to match the mechanical properties of the skin, with the tensile modulus and compressive modulus reaching 32.2 kPa and 121.9 kPa, respectively. In vitro and in vivo experiments confirmed that this Janus hydrogel achieved nearly complete wound closure (u0026gt;96%) within 14 days by promoting antibacterial activity, anti-inflammatory effects, epithelialization, angiogenesis, and collagen deposition. The straightforward one-step integration of biocompatible CS and PEG to produce asymmetric hydrogels creates new opportunities for manufacturing adhesive dressings in advanced tissue repair scenarios.
