Tissue regeneration has raised intensive attention due to its great significance in overcoming various diseases resulting from different injuries. Since the COVID-19 pandemic, mRNA therapeutics have emerged as innovative strategies in the prevention and treatment of diseases due to their unique advantages. Compared to traditional regenerative strategies, mRNA therapy offers rapid translation into proteins with low production cost and high modifiability. Herein, we discuss the progress in the key processes of mRNA therapy, focusing on therapeutic mRNA modification and delivery carriers. The preclinical and clinical studies of mRNA therapeutics for regeneration of cardiac, lung, liver, kidney, locomotor system, skin lesions and neurological disorders were summarized comprehensively. Developing strategies to reduce immunogenicity and off-target effects, as well as optimization of the delivery system may accelerate the pace of clinical translation.

Photodynamic therapy (PDT) has significant potential in the treatment of dermatological, oncological, and nonneoplastic conditions through the induction of cell death, immune regulation, antimicrobial effects, etc. However, the response of some patients is unsatisfactory, and there is a lack of an ideal protocol for multiple specific diseases (subtypes) to choose the proper photosensitizer (PS), light source, and dose. A thorough understanding of the underlying mechanism is integral to solving these problems, and cell death has gained much attention. In addition to apoptosis, autophagy, and necrosis, several novel cell death pathways, such as necroptosis, mitotic catastrophe, paraptosis and pyroptosis, have been reported in PDT treatment. The type of induced cell death depends on the dose of PDT, the subcellular location of PSs, and the regulation of signaling pathways. In addition, different types of cell death induced by the same type of PDT, such as apoptosis and autophagy, may interact with each other. Some types of cell death can also trigger immunogenic cell death (ICD), which can ignite an immune response against antigens derived from dying/dead cells and present improved antitumor effects. On the basis of these mechanisms, several strategies, such as targeted PSs, PDT combined with immunotherapy and ICD-based vaccines, have been proposed to improve therapeutic efficacy. Future studies are needed to elucidate the relationship between cell death and therapeutic effects and to shed new light on the exploration of precise PDT for specific patients.

With the rising global prevalence of diabetes, the rate of chronic wounds associated with this disease is also escalating. Although the mechanisms underlying this trend are not fully understood, accumulating evidence suggests a critical role for reactive oxygen species (ROS). Increased blood glucose levels, bacterial infections, and impaired energy utilization lead to an imbalance between oxidative and antioxidant responses, resulting in ROS accumulation. The cellular antioxidant system can manage a small amount of ROS; however, excessive exogenous ROS acts upon the cell membrane or even penetrates the cell, consequently affecting its activity. Excessive ROS cause enhanced expression of inflammatory factors, impaired cellular proliferation, vascular vessel damage, and extracellular matrix remodeling disturbance, ultimately hindering diabetic wound healing. The regulation of ROS during wound healing is intricate and involves diverse mechanisms throughout the entire wound-healing process. This review provides a systematic overview of the relationship between ROS and inflammatory signaling pathways in diabetic wounds along with the most recent antioxidant strategies targeting these pathways. The aim of this review was to outline effective strategies for mitigating oxidative stress in chronic wounds and to provide novel insights into future research.

Lung cancer remains one of the deadliest cancers globally, which may be attributed in part to a limited understanding of its development. Therefore, exploration of the fundamental processes of lung cancer and innovative therapies is imminent. Recently, lung cancer immunotherapy has become a crucial topic of interest, and it pertains to the metabolism in lung tumor microenvironment. In particular, glutamine metabolism plays a pivotal role in lung cancer immunotherapy. This review summarizes the crosstalk between glutamine metabolism and the lung tumor immune microenvironment, and explores potential strategies of glutamine metabolism as an enhancement of lung cancer immunotherapy. It also discusses the potential of traditional Chinese medicine in regulating glutamine metabolism in lung cancer immunotherapy. This review may offer valuable insights and promising directions for future studies on this subject.

Osteosarcoma (OS), the most common primary bone tumor in children and young adults, poses significant clinical challenges. In this study, we investigated the role of exosomes—key mediators of intercellular communication—in OS progression and identified potential therapeutic targets. Functional assays in cellular and animal models demonstrated that OS-derived exosomes markedly enhanced tumor proliferation, migration, and invasion. Data-independent acquisition-based mass spectrometry analysis revealed a notable enrichment of the proto-oncogene tyrosine-protein kinase YES1 in these exosomes. Bioinformatics and clinical investigations further showed that YES1 is overexpressed in multiple cancers and correlates with poor outcomes; specifically, in OS, elevated YES1 levels were associated with reduced overall survival and adverse prognoses. PCR, Western blotting, and immunohistochemistry (IHC) of clinical samples confirmed its high expression in OS tissues relative to normal counterparts. Mechanistic studies using YES1 knockdown (shYES1) and overexpression (OE YES1) models, coupled with exosome supplementation and pathway modulators, revealed a critical role for ERK phosphorylation in mediating YES1-driven oncogenic behaviors. In shYES1 cells, tumor proliferation, migration, and invasion were significantly impaired, partially rescued by exosome supplementation, and further suppressed by the inhibitor of MAPK. Conversely, in OE YES1 cells, these malignant phenotypes were markedly enhanced, exacerbated by exosomes, and further promoted by the agonist of MAPK. Western blot analyses supported these observations, showing reduced p-MEK and p-ERK but increased p-p38 and p-JNK upon YES1 knockdown, with opposite trends in the OE YES1 group; these phosphorylation changes were reversed or attenuated by EGF/IL-1beta or U0126/SB-203580 treatment, respectively, without altering total protein levels of MEK, JNK, p38, and ERK. Finally, multiplex IHC validated bioinformatics predictions, demonstrating that YES1 expression is closely linked to immune-related pathways in OS tissues. Collectively, these findings underscore the pivotal role of exosomal YES1 in OS progression and tumor immunology, highlighting its promise as a biomarker and therapeutic target. By illuminating its function in cancer behavior and immune interactions, this study offers novel insights into improving patient outcomes in OS.

Small non-coding RNAs (ncRNAs) are functional molecules contained within extracellular vesicles (EVs) that modulate various physiological and pathological processes. This study provides a comprehensive expression profile of seven types of small ncRNAs in serum- and plasma-derived EVs under various conditions. Both large EVs (lEVs) and small EVs (sEVs) contain high proportions of miRNAs (∼28.2% in lEVs and ∼20.8% in sEVs) and ribosomal RNAs (∼24.0% in lEVs and ∼19.1% in sEVs). lEVs are enriched with more transfer RNA (∼38.8%) than sEVs, whereas sEVs have a greater abundance of Y RNA (∼22.5%). Notably, Y RNA is more abundant in sEVs obtained from aged samples (age ≥60 years), a pattern not observed in lEVs. Small ncRNAs are more diverse in serum-derived EVs than plasma-derived EVs. There is also a high degree of overlap (>50%) in the top 100 small ncRNAs identified in lEVs and sEVs. The miRNAs hsa-miR-16-5p, hsa-let-7a-5p, hsa-miR-142-3p, and hsa-miR-103-3p are consistently among the top 10 highly expressed small ncRNAs in plasma- and serum-derived lEVs as well as in peripheral blood mononuclear cells. Serum-derived sEVs in glioblastoma, breast cancer, prostate cancer, and gastric cancer contain specific, highly expressed miRNAs, snoRNAs, small nuclear RNAs, and piRNAs. These results elucidate the patterns of small ncRNA cargoes within lEVs and sEVs derived from serum and plasma under various physiological and pathological conditions and offer valuable insights for future diagnostic and therapeutic applications.

Selenium (Se) is a trace element that fulfills vital functions in the organism. Over the past few years, numerous studies have revealed the profound connection between Selenium and its therapeutic potential in addressing various viral infectious diseases. Selenium can boost the activity of immune cells and counteract oxidative damage caused by free radicals to prevent the replication of viruses. Studies have shown that Selenium protects against a wide range of viruses such as DNA viruses, hepatitis B virus, RNA viruses, human immunodeficiency virus and coxsackie virus. Selenium is probably one of the research directions for antiviral drugs in the future. This review summarizes the use of Selenium in antiviral therapy and its research progress.

Metabolic diseases, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD), are increasingly common worldwide, posing a significant public health challenge. Recent research has revealed a complex interplay between these metabolic disorders and interferon (IFN) immune responses. As key immune regulators, interferons coordinate the host's defense against viral infections and are essential for maintaining immune homeostasis. However, metabolic dysregulation can significantly disrupt IFN signaling pathways, affecting the intensity and efficiency of immune responses. Conversely, alterations in IFN signaling can influence the onset and progression of metabolic diseases. This review explores the mechanisms by which metabolic diseases modulate IFN responses, focusing on how obesity, diabetes, and MAFLD alter IFN signaling. Additionally, we examine the implications of the changes in IFN immune responses for the progression of metabolic diseases. By synthesizing current research, this review aims to elucidate the interplay between IFN immune responses and common metabolic diseases, offering insights for future research and clinical applications in the field of IFN-related metabolic diseases.

Isomeric interference is essential in mass spectrometry (MS) analysis of steroid hormones. This study aims to investigate the specificity of liquid chromatography-tandem MS (LC-MS/MS) for measuring 18-hydroxycorticosterone (18-OHB) and to develop a validated LC-MS/MS method. To identify the interfering substance on 18-OHB quantification in plasma, high-performance liquid chromatography-tandem time-of-flight mass spectrometry was used for the retention time comparison and the fragment characteristics matching. 18-OHB, cortisone, and cortisol could be chromatographically separated using water containing 0.025 mM ammonium fluoride and acetonitrile on the UPLC BEH C8 column. The interference of 18-OHB with similar ion transitions was finally identified as 20β-dihydrocortisone (20α-DHE), instead of cortisone, cortisol, or 20β-dihydrocortisone. By using optimized chromatographic conditions, 18-OHB, and 20α-DHE were separated well and the linearities were ≥0.999. The recovery rates ranged from 94.59% to 105.27% for 18-OHB and 85.21%–101.23% for 20α-DHE. The total coefficient of variations in the precision evaluation was ≤4.6% for 18-OHB and ≤4.3% for 20α-DHE. The medians of 18-OHB and 20α-DHE levels in patients with primary aldosteronism were 0.48 ng/mL and 0.14 ng/mL, respectively. This study explored the potential risks associated with isomeric interference in LC-MS/MS for 18-OHB quantification and established a robust LC-MS/MS method for detecting plasma 18-OHB and 20α-DHE. Comprehensively assessing the effect of the underlying isomers when using LC-MS/MS for hormone measurements is recommended.

Lateral flow assays (LFAs) are widely applicable in clinical point-of-care testing (POCT) due to their unique advantages such as simplicity, rapidity, and cost-effectiveness. However, their sensitivity is often constrained by the background autofluorescence of the biological sample, the self-matrix, or the readout technique, thereby leading to overlooking trace amounts of biomarkers present in early disease. In recent years, various nanomaterials-based methods have been developed to address this issue, including the time-gated technique, wavelength-differentiated strategy and external modulated strategy for separation of background autofluorescence to minimize interference from biological samples. This review provides a comprehensive overview of various low-background luminescent nanoparticles (LBLNPs)-enhanced LFA systems, focusing on analyzing the underlying mechanism of these nanomaterials in improving the sensitivity and accuracy of the LFAs platform in clinical diagnosis. Representative examples are selected to demonstrate the clinical potential of these nanomaterials in detecting disease-associated biomarkers in various samples including blood, urine, saliva et al. Finally, unresolved challenges and future development prospects are briefly discussed.

Breast cancer often develops drug resistance during chemotherapy, and immunotherapeutic agents always exhibit ineffectiveness when used as a single treatment; thus, it is necessary to develop a chemo-immunotherapy strategy in clinics. However, there is still a challenge to evaluate the chemo-immunotherapy efficacy by conventional 2D cell culture and animal models. In this study, we developed a facile automated multiple-well platform for fabricating tumor associated macrophages (TAMs)-immunized breast cancer organoids in alginate hydrogels. An automated robotic microinjection system was used for building alginate hydrogels in situ and seeding mixed cell suspensions of breast cancer cells and TAMs into hydrogels to form organoids. The induced drug resistance to epirubicin was observed in breast cancer organoids with TAMs, but it could be inhibited by targeted immunotherapy PLX3397. The synergistic effects were also evaluated in several co-administration strategies of PLX3397 in combination with epirubicin. The RNA-seq and quantitative polymerase chain reaction were further used to examine gene transcription levels in the co-administration and find out three genes (IL6, CD37, and GLS2) with significant differences, which were involved in the tumor necrosis factor signaling, PI3K-Akt signaling and epidermal growth factor receptor tyrosine kinase inhibitor resistance pathway. The results demonstrated that the automated multiple-well platform showed the potential to replace the conventional bulk culture method in evaluating the therapeutic effects of chem-immunotherapy.

Gut microbiota play a key role in cancer immunotherapy and regulating gut microbiota provides new strategies with great potential for cancer therapeutics. Several gut microbiota-based strategies, such as antibiotic treatment and fecal microbiota transplantation, have gained certain achievements in enhancing cancer immunotherapy, while the potential risk of biosafety and the destruction of commensal microbiota limit their further applications. Nanomaterials with excellent capabilities in delivering drugs and modulating bacteria may provide specific solutions for these limitations, and have shown promising potential in manipulating the gut microbiota to boost cancer immunotherapy. In this perspective, we reviewed the breakthroughs of nanomaterials in modulating the gut microbiota and their metabolites to enhance cancer immunotherapy, and further discussed the challenges and opportunities in this emerging field. It is anticipated that this perspective will offer new insights on the rational design of nanomaterials to regulate the gut microbiota for enhanced cancer immunotherapy, fostering clinical translation and ultimately benefiting patients.