Effective oral therapy for inflammatory bowel disease (IBD) requires overcoming gastrointestinal barriers to modulate the dysregulated mucosal niche. Here, we present edible nanovesicles derived from Perilla frutescens (PLENs) as an intrinsically stable, bioactive nanotherapeutic. Multi-omics profiling defined a robust lipid-bilayer architecture encapsulating a synergistic cargo of proteins, miRNAs, and antioxidant metabolites. This structural integrity enabled PLENs to survive gastrointestinal transit and exhibit preferential fluorescence localization with prolonged retention in the inflamed colonic region, as indicated by in vivo imaging. Upon localization, PLENs executed a "dual-hit" therapeutic strategy: they reprogrammed the immune microenvironment, accompanied by reduced activation of the TLR4/MyD88-NF-κB axis and a phenotypic shift from pro-inflammatory M1 to reparative M2 macrophages. Concurrently, PLENs fundamentally restructured the gut ecosystem, accompanied by enrichment of taxa linked to saccharolytic fermentation and recovery of cecal short-chain fatty acids. Notably, fecal microbiota transplantation (FMT) further supported that this microbial remodeling contributed to the protective phenotype, highlighting the microbiome as an important component of efficacy.

Gastric cancer remains a leading cause of cancer-related mortality, with limited treatment options and a poor prognosis. Mesenchymal stem cells (MSCs) possess inherent tumor-homing ability but exhibit modest efficacy against solid tumors. Enhancing both tumor targeting and immune activation through genetic modification may improve the therapeutic potential of these approaches. To evaluate the anti-cancer efficacy of human umbilical cord–derived MSCs (HUC-MSCs) genetically modified to co-express C-X-C chemokine receptor type 4 (CXCR4) and TNFSF14 (LIGHT) against gastric cancer in vitro and in vivo. HUC-MSCs were transduced via lentiviral vectors to generate dual-gene–engineered Tg-HUC-MSCs. In vitro, their effects on HGC-27 gastric cancer cells were assessed using the scratch wound migration assay and Annexin V/PI apoptosis analysis. In vivo, BALB/c nude mice bearing subcutaneous HGC-27 xenografts were treated with Tg-HUC-MSCs, unmodified HUC-MSCs, or a control. Tumor growth was monitored by caliper measurements. Excised tumors were analyzed histologically with hematoxylin–eosin staining and by Ki-67 immunohistochemistry. Tg-HUC-MSCs significantly inhibited HGC-27 cell migration and induced higher apoptosis rates than unmodified HUC-MSCs in vitro (p < 0.001). In vivo, Tg-HUC-MSCs markedly reduced tumor volume, increased necrotic areas, and decreased Ki-67 proliferation indices compared to controls (p < 0.001). Elevated CXCR4 and LIGHT expression correlated with improved tumor targeting and enhanced immune-mediated tumor cell killing. Dual-gene–engineered HUC-MSCs (CXCR4 + TNFSF14) demonstrated superior tumor-homing and anti-cancer activity against gastric cancer cells in vitro and in vivo, representing a promising cell-based therapeutic strategy for solid tumors.

The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) due to the aggregation of Lewy bodies is the hallmark of Parkinson's disease (PD). ROS play a key role in the formation of Lewy bodies, thus leading to mitochondrial dysfunction and the apoptosis of neurons. A rotating magnetic field (RMF) is an emerging noninvasive technique for the prevention of neurodegenerative disorders. To investigate the potential therapeutic effects of RMS in PD, we subjected an experimental mouse model to RMF. CblC mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg, i.p., once daily for 5 days), followed by RMF treatment at a frequency and intensity of 4 Hz and 0.4 T, respectively. The daily 2-h RMF treatment was continued for a period of 6 months. We examined the effects of RMF on motor functions, the aggregation of Lewy bodies and the integrity and viability of total and dopaminergic neurons in the SNpc and striatal regions. We further performed transcriptomic analysis of SNpc tissue from PD and SHAM mice. Our results showed that exposure to RMF improved motor functions, enhanced neuronal cell viability and protected neuronal integrity in a PD mouse model. We further showed that RMF diminishes the number of aggregated Lewy bodies in neurons and reduces ROS production. Overall, the results of the transcriptomic analysis revealed that RMF promoted the expression of anti-apoptotic genes rather than proapoptotic genes that are specifically involved in mitochondrial apoptosis.

Lung cancer is a leading cause of global cancer mortality, highlighting the need of effective, low-toxicity targeted therapies. Virus-like particles (VLPs) are a promising platform due to their virus-mimicry structure, multifunctionality, and safety. We developed integrin alpha v beta 3-targeting VLPs using human bocavirus 1 (HBoV1) VP3 protein for lung cancer-specific doxorubicin (DOX) delivery. And RGD (Arg-Gly-Asp) was inserted into the VP3 VR-I region (residues 80-95) to generate mutant VLPs (M-VLPs). Both wild-type (Wt-VP3) and mutant (M-VP3) proteins were expressed in Escherichia coli (E. coli), purified, and self-assembled into uniform nanoparticles. DOX was conjugated via EDC/NHS chemistry to form M-VLPs-DOX. M-VLPs exhibited significantly enhanced uptake in alpha v beta 3-overexpressing A549 (lung cancer) and HUVEC cells compared to wild-type VLPs (Wt-VLPs), but not in low-alpha v beta 3 MCF-7 cells. Under simulated tumor microenvironmental conditions (similar to pH 5.5), M-VLPs-DOX released 48% DOX over 24 h, substantially exceeding the 19% at physiological pH 7.4. M-VLPs-DOX demonstrated superior cytotoxicity against A549 cells than free DOX or Wt-VLPs-DOX. M-VLPs-DOX significantly elevated reactive oxygen species (ROS) and DNA damage, promoting apoptosis. ROS subsequently converted DOX into quinone radicals, further amplifying DNA breaks. Uptake occurred primarily via clathrin-mediated endocytosis. In vivo, M-VLPs-DOX maintained stable body weights without significant organ toxicity, unlike free DOX, which caused hepatocyte ballooning degeneration. These results show that RGD-modified HBoV1-VLPs enable integrin alpha v beta 3-mediated tumor targeting, significantly enhancing DOX delivery to lung cancer. This strategy synergistically amplifies oxidative stress and DNA damage, boosting antitumor efficacy while reducing systemic toxicity, supporting the optimization of VLP-based nanocarriers for targeted cancer therapy.

Hyperuricemia-associated renal injury involves coordinated disturbances in urate transport, tubular inflammation, and gut-kidney metabolic homeostasis. Here, we evaluated Perilla frutescens-derived exosome-like nanovesicles (PLENs) as an orally deliverable natural vesicle platform for this condition. PLENs showed stable nanoscale vesicular features and maintained structural compatibility under simulated gastrointestinal conditions. In potassium oxonate/hypoxanthine-induced hyperuricemic mice, oral PLENs reduced urate burden, preserved renal function, and alleviated tubular injury and early fibrotic remodeling. Mechanistically, PLENs improved renal urate transporter balance by restoring ABCG2 and suppressing URAT1/GLUT9, accompanied by reduced NLRP3-associated inflammatory stress. Fluorescence imaging supported a gastrointestinal-dominant exposure pattern, consistent with an intestine-facing mode of action. PLENs also strengthened colonic barrier integrity, remodeled intestinal urate transporter expression, reshaped cecal dysbiosis, restored major short-chain fatty acid outputs, and redirected intestinal metabolic pathways related to fermentation, redox regulation, amino acid metabolism, and ABC transport. These findings identify PLENs as oral natural nanovesicles that mitigate hyperuricemia-associated renal injury through integrated regulation of renal urate handling and the gut-kidney biointerface.

Current therapeutic strategies for Parkinson’s disease (PD) focus exclusively on symptomatic management without addressing underlying disease progression. Despite decades of research emphasizing the enhancement of the cellular defense pathway, disease-modifying treatments remain elusive. We evaluated rotating magnetic field (RMF) therapy in A53T transgenic mice harboring a familial PD-associated mutation. Transgenic and wild-type animals (n = 8 per group) received RMF treatment (4 Hz, 0.4 T, 2 h daily) for six months. Motor function, muscle strength, and neuropathological markers were assessed. Comprehensive transcriptomic and proteomic analyses were performed to elucidate the molecular mechanisms involved. Untreated A53T transgenic mice exhibited progressive motor decline (51

Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/ PS1 mice. These protective effects and the underlying mechanism were also observed in A beta 25-35-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.

BACKGROUND:Plant-derived extracellular vesicles (PDEVs) are vital for intercellular material exchange and information transfer. They significantly regulate cellular functions, tissue repair, and self-defense mechanisms. OBJECTIVE:This review summarizes the formation pathways, composition, and potential applications of PDEVs in anti-tumor research and drug delivery systems. METHODS:We conducted a literature search using keywords such as "plant-derived extracellular vesicles," "exosomes," "drug delivery," "isolation and purification," "stability," "anti-tumor," and "tumor therapy" in databases including PubMed, Web of Science, and Scopus. We examined studies on the formation pathways of PDEVs, including fusion of multivesicular bodies with the plasma membrane, exosome-positive organelles, and vacuole release. We also reviewed isolation and purification techniques critical for studying their biological functions. Furthermore, we analyzed research on the application of PDEVs in cancer therapy, focusing on their inhibitory effects in various cancer models and their role as carriers in drug delivery systems. RESULTS:PDEVs have demonstrated potential in anti-tumor research, particularly with vesicles from plants like tea, garlic, and Artemisia annua showing inhibitory effects in breast, lung, and gastric cancer models. Additionally, PDEVs serve as effective carriers in drug delivery systems, offering possibilities for developing ideal therapeutic solutions. CONCLUSION:While PDEVs show promise in cancer treatment and drug delivery, challenges such as standardization, storage stability, and elucidation of action mechanisms remain. Further research is needed to overcome these challenges and advance the clinical translation of PDEVs.

In this review, we have discussed the invasive and non-invasive treatment options for Parkinson’s Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.

Background:Acute kidney injury (AKI) results from cisplatin chemotherapeutic agents in 30 %-46 % of patients, but clinically effective preventive and therapeutic approaches are lacking. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) have potential in tissue repair, but the mechanism by which they attenuate cisplatin-induced kidney injury is unknown. Objective:To explore the therapeutic effect of BMSCs-exo on cisplatin-induced AKI and to analyze the key molecular mechanism involved. Methods and materials:BMSCs-exo were extracted via ultracentrifugation and identified via transmission electron microscopy, nanoparticle analysis and Western blot. C57BL/6 mice were divided into a control group (Con), a cisplatin model group (Cis), and a BMSCs-exo treatment group (BMSCs-exo), and renal function was dynamically tested. PAS staining was used to observe histopathological changes in mouse kidney tissues, while immunohistochemistry was employed to assess the expression levels of Wnt4, β-catenin, FZD5, CD31, and the tubular injury markers NGAL and KIM1. Western blot was used to detect the expression of Wnt4, β-catenin, FZD5 and CD31. High-throughput sequencing was used to screen for differential miRNAs, and GO/KEGG enrichment analysis of target genes was performed. Results:Blood creatinine and urea nitrogen levels were significantly higher in the Cis group than in the Con group, and renal tubular epithelial cells exhibited necrosis, confirming successful AKI model establishment. BMSCs-exo alleviated renal dysfunction, histopathological alterations, and tubular injury in vivo, as evidenced by NGAL and KIM1 expression. We further demonstrated that BMSCs-exo specifically localized to the injured kidney. MiRNA sequencing of renal tissues from the Con, Cis and BMSCs-exo groups identified mmu-miR-874-3p-enriched in Wnt signaling and angiogenesis pathways-as a key mediator of the renoprotective effects of BMSCs-exo, with FZD5 as its downstream target. Moreover, treatment with BMSCs-exo markedly prevented microvascular loss. In the BMSCs-exo group, Wnt4, β-catenin and CD31 expression were upregulated, whereas FZD5 expression was downregulated, consistent with the immunohistochemistry results. Conclusions:BMSCs-exo protect kidneys against cisplatin-induced AKI(Cis-AKI) by attenuating injury to the renal microvasculature and tubule epithelial cells, primarily through mmu-miR-874-3p-mediated inhibition of FZD5 activation and promotion of Wnt/β-catenin pathway activation.

Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system. Forskolin (FSK) is a plant-derived diterpene with excellent immunomodulatory properties and has not been systematically reported for treating MS. This study investigated the therapeutic effects of FSK on cellular and animal MS models and preliminarily explored related mechanisms. The results showed that FSK suppressed the inflammatory response, reduced the expression of STEAP4, and relieved iron deposition in BV-2 cells pretreated by LPS at the cellular level. Meanwhile, at the animal level, FSK treatment halted the progression of experimental autoimmune encephalomyelitis (EAE), alleviated the damage at the lesion sites, reduced the concentration of proinflammatory factors in peripheral blood, and inhibited the immune response of peripheral immune organs in EAE mice. Besides, FSK treatment decreased the expression of STEAP4 in the spinal cord and effectively restored the iron balance in the brain, spinal cord, and serum of EAE mice. Further investigation showed that FSK can reduce IL-17 expression, prevent the differentiation of TH17 cells, and inhibit the calcium signaling pathway. Thus, these results demonstrate that FSK may have the potential to treat MS clinically.

With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced in vivo rat model, and an MPS-induced in vitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH.

Neuroinflammation, triggered by aberrantly activated microglia, is widely recognized as a key contributor to the initiation and progression of Alzheimer’s disease (AD). Microglial activation in the central nervous system (CNS) can be classified into two distinct phenotypes: the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. In this study, we investigated the effects of a non-invasive rotating magnetic field (RMF) (0.2T, 4Hz) on cognitive and memory impairments in a sporadic AD model of female Kunming mice induced by AlCl3 and D-gal. Our findings revealed significant improvements in cognitive and memory impairments following RMF treatment. Furthermore, RMF treatment led to reduced amyloid-beta (Aβ) deposition, mitigated damage to hippocampal morphology, prevented synaptic and neuronal loss, and alleviated cell apoptosis in the hippocampus and cortex of AD mice. Notably, RMF treatment ameliorated neuroinflammation, facilitated the transition of microglial polarization from M1 to M2, and inhibited the NF-кB/MAPK pathway. Additionally, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice. In cellular experiments, RMF promoted the M1-M2 polarization transition and enhanced amyloid phagocytosis in cultured BV2 cells while inhibiting the TLR4/NF-кB/MAPK pathway. Collectively, these results demonstrate that RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway. These findings suggest the promising therapeutic applications of RMF in the clinical treatment of AD.

Ulcerative colitis (UC) is a prevalent inflammatory disorder that emerges in the colon and rectum, exhibiting a rising global prevalence and seriously impacting the physical and mental health of patients. Significant challenges remain in UC treatment, highlighting the need for safe and effective long-term therapeutic approaches. Heralded as a promising physical treatment, the rotating magnetic field (RMF) demonstrates safety, stability, manageability, and efficiency. This study delves into RMF’s potential in mitigating DSS-induced UC in mice, assessing disease activity indices (DAI) and pathological alterations such as daily body weight, fecal occult blood, colon length, and morphological changes. Besides, several indexes have been detected, including serum concentrations of pro-inflammatory cytokines (IL6, IL-17A, TNF-α, IFN-γ) and anti-inflammatory cytokines (TGF-β, IL-4, IL-10), the ratio of splenic CD3+, CD4+, and CD8+ T cells, the rate of apoptotic colonic cells, the expression of colonic inflammatory and tight junction-associated proteins. The results showed that RMF had beneficial effects on the decrease of intestinal permeability, the restoration of tight junctions, and the mitigation of mitochondrial respiratory complexes (MRCs) by attenuating inflammatory dysfunction in colons of DSS-induced UC model of mice. In conclusion, this study demonstrates that RMF attenuates colonic inflammation, enhances colonic tight junction, and alleviates MRCs impairment by regulating the equilibrium of pro-inflammatory and anti-inflammatory cytokines in UC mice, suggesting the potential application of RMF in the clinical treatment of UC.

Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and performed liver transcriptome sequencing analysis at various time points within a 24-h period. Subsequently, we monitored the autonomic activity and food intake in these male mice for six days post-sleep deprivation. We observed alterations in sleep-wake and feeding rhythms in the first two days following sleep deprivation. Additionally, we also observed a decrease in 24-h serum-glucose levels. Liver transcriptome sequencing has shown that sleep deprivation induces the rhythmic transcription of a large number of genes, or alters the rhythmic properties of genes, which were then significantly enriched in the carbohydrate, lipid, and protein metabolism pathways. Our findings suggest that under conditions of prolonged sleep deprivation, the expression of metabolic-related genes in the liver was reset, leading to changes in the organism’s metabolic state to ensure energy supply to sustain prolonged wakefulness.

Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.

The toxicity of CdSe/ZnS quantum dots (QDs) in the environment and biological systems has become a major concern for the nanoparticle community. However, the potential toxicity of QDs on immune cells and its corresponding immune functions remains poorly understood. In this study, we investigated the immunotoxicity of CdSe/ZnS QDs using the in vitro in macrophages and lymphocytes and in vivo in BALB/c mice.

As one of the common variable magnetic fields, rotating magnetic field (RMF) plays a crucial role in modern human society. The biological effects of RMF have been studied for over half a century, and various results have been discovered. Several reports have shown that RMF can inhibit the growth of various types of cancer cells in vitro and in vivo and improve clinical symptoms of patients with advanced cancer. It can also affect endogenous opioid systems and rhythm in central nerve systems, promote nerve regeneration and regulate neural electrophysiological activity in the human brain. In addition, RMF can influence the growth and metabolic activity of some microorganisms, alter the properties of fermentation products, inhibit the growth of some harmful bacteria and increase the susceptibility of antibiotic-resistant bacteria to common antibiotics. Besides, there are other biological effects of RMF on blood, bone, prenatal exposure, enzyme activity, immune function, aging, parasite, endocrine, wound healing, and plants. These discoveries demonstrate that RMF have great application potential in health care, medical treatment, fermentation engineering, and even agriculture. However, in some cases like pregnancy, RMF exposure may need to be avoided. Finally, the specific mechanisms of RMF's biological effects remain unrevealed, despite various hypotheses and theories. It does not prevent us from using it for our good.

Reticulocalbin-1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN-1) expression and promotes AML cell pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.