Exploring the relationship between infectious agents and autoimmune diseases: a review.

The relationship between infectious agents and autoimmune diseases is a complex issue. In recent years, increasing clinical cases have indicated that infectious agents play an important role in the development of autoimmune diseases. Molecular mimicry is currently widely regarded as the primary pathogenic mechanism of various autoimmune diseases in humans. Components of infectious agents can undergo molecular mimicry with components in patients' bodies, leading to the development of various autoimmune diseases. In this article, we provide a brief overview of current research of the current research status on the relationship between infectious agents and autoimmune diseases, and describe our current understanding of their mechanisms of action in order to better understand the pathogenesis, diagnosis, and treatment of autoimmune diseases.

Advances in cell membrane-based biomimetic nanodelivery systems for natural products.

Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products.

The effect of macrophages and their exosomes in ischemic heart disease.

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.

Identification and validation of an immune-derived multiple programmed cell death index for predicting clinical outcomes, molecular subtyping, and drug sensitivity in lung adenocarcinoma.

OBJECTIVES: Comprehensive cross-interaction of multiple programmed cell death (PCD) patterns in the patients with lung adenocarcinoma (LUAD) have not yet been thoroughly investigated. METHODS: Here, we collected 19 different PCD patterns, including 1911 PCD-related genes, and developed an immune-derived multiple programmed cell death index (MPCDI) based on machine learning methods. RESULTS: Using the median MPCDI scores, we categorized the LUAD patients into two groups: low-MPCDI and high-MPCDI. Our analysis of the TCGA-LUAD training cohort and three external GEO cohorts (GSE37745, GSE30219, and GSE68465) revealed that patients with high-MPCDI experienced a more unfavorable prognosis, whereas those with low-MPCDI had a better prognosis. Furthermore, the results of both univariate and multivariate Cox regression analyses further confirmed that MPCDI serves as a novel independent risk factor. By combining clinical characteristics with the MPCDI, we constructed a nomogram that provides an accurate and reliable quantitative tool for personalized clinical management of LUAD patients. The findings obtained from the analysis of C-index and the decision curve revealed that the nomogram outperformed various clinical variables in terms of net clinical benefit. Encouragingly, the low-MPCDI patients are more sensitive to commonly used chemotherapy drugs, which suggests that MPCDI scores have a guiding role in chemotherapy for LUAD patients. CONCLUSION: Therefore, MPCDI can be used as a novel clinical diagnostic classifier, providing valuable insights into the clinical management and clinical decision-making for LUAD patients.

Recent progress in biomimetic nanomedicines based on versatile targeting strategy for atherosclerosis therapy.

Atherosclerosis (AS) is considered to be one of the major causes of cardiovascular disease. Its pathological microenvironment is characterised by increased production of reactive oxygen species, lipid oxides, and excessive inflammatory factors, which accumulate at the monolayer endothelial cells in the vascular wall to form AS plaques. Therefore, intervention in the pathological microenvironment would be beneficial in delaying AS. Researchers have designed biomimetic nanomedicines with excellent biocompatibility and the ability to avoid being cleared by the immune system through different therapeutic strategies to achieve better therapeutic effects for the characteristics of AS. Biomimetic nanomedicines can further enhance delivery efficiency and improve treatment efficacy due to their good biocompatibility and ability to evade clearance by the immune system. Biomimetic nanomedicines based on therapeutic strategies such as neutralising inflammatory factors, ROS scavengers, lipid clearance and integration of diagnosis and treatment are versatile approaches for effective treatment of AS. The review firstly summarises the targeting therapeutic strategy of biomimetic nanomedicine for AS in recent 5 years. Biomimetic nanomedicines using cell membranes, proteins, and extracellular vesicles as carriers have been developed for AS.

pH-responsive size-adjustable liposomes induce apoptosis of fibroblasts and macrophages for rheumatoid arthritis treatment.

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.

Enhancing the stability of mung bean-based milk: Insights from protein characteristics and raw material selection.

Plant-based milk (PBM) alternatives are gaining popularity worldwide as the change of consumers' nutritional habits and health attitudes. Mung beans, recognized for their nutritional value, have gained attention as potential ingredients for PBM. Nevertheless, mung bean-based milk (MBM) faces instability issues common to other plant-based milks. This study investigated the factors influencing MBM stability focusing on raw materials. We selected 6 out of 20 varieties based on their MBM centrifugation sedimentation rates, representing both stable and unstable MBM. Stable MBM exhibited distinct advantages, including reduced separation rate, smaller particle size, lower viscosity, fewer protein aggregates, higher soluble protein content, and increased consumer acceptance. Major nutritional components such as protein, starch, and lipids were not significant different between stable and unstable MBM varieties. The pivotal distinction may lay in the protein properties and composition. Stable MBM varieties exhibited significantly improved protein solubility and emulsion stability, along with elevated concentrations of legume-like acidic subunits, basic 7S proteins, and 28 kDa and 26 kDa vicilin-like subunits. The increasement of these proteins likely contributed to the improvement in protein characteristics that affect MBM stability. These findings offer valuable insights for raw material selection and guidance for future mung bean breeding to enhance mung bean milk production.

A Machine Learning Computational Framework Develops a Multiple Programmed Cell Death Index for Improving Clinical Outcomes in Bladder Cancer.

Comprehensive action patterns of programmed cell death (PCD) in bladder cancer (BLCA) have not yet been thoroughly investigated. Here, we collected 19 different PCD patterns, including 1911 PCD-related genes, and developed a multiple programmed cell death index (MPCDI) based on a machine learning computational framework. We found that in the TCGA-BLCA training cohort and the independently validated GSE13507 cohort, the patients with high-MPCDI had a worse prognosis, whereas patients with low-MPCDI had a better prognosis. By combining clinical characteristics with the MPCDI, we constructed a nomogram. The C-index demonstrated that the nomogram was significantly more accurate compared to other variables, including MPCDI, age, gender, and clinical stage. The results of the decision curve analysis demonstrated that the nomogram had a better net clinical benefit compared to other clinical variables. Subsequently, we revealed the heterogeneity of BLCA patients, with significant differences in terms of overall immune infiltration abundance, immunotherapeutic response, and drug sensitivity in the two MPCDI groups. Encouragingly, the high-MPCDI patients showed better efficacy for commonly used chemotherapeutic drugs than the low-MPCDI patients, which suggests that MPCDI scores have a guiding role in chemotherapy for BLCA patients. In conclusion, the MPCDI developed and verified in this study is not only an emerging clinical classifier for BLCA patients, but it also serves as a reliable forecaster for both chemotherapy and immunotherapy, which can guide clinical management and clinical decision-making for BLCA patients.

Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy.

Tumor development and metastasis are closely related to the complexity of the metabolism network. Recently, metabolism reprogramming strategies have attracted much attention in tumor metabolism therapy. Although there is preliminary success of metabolism therapy agents, their therapeutic effects have been restricted by the effective reaching of the tumor sites of drugs. Nanodelivery systems with unique physical properties and elaborate designs can specifically deliver to the tumors. In this review, we first summarize the research progress of nanodelivery systems based on tumor metabolism reprogramming strategies to enhance therapies by depleting glucose, inhibiting glycolysis, depleting lactic acid, inhibiting lipid metabolism, depleting glutamine and glutathione, and disrupting metal metabolisms combined with other therapies, including chemotherapy, radiotherapy, photodynamic therapy, etc. We further discuss in detail the advantages of nanodelivery systems based on tumor metabolism reprogramming strategies for tumor therapy. As well as the opportunities and challenges for integrating nanodelivery systems into tumor metabolism therapy, we analyze the outlook for these emerging areas. This review is expected to improve our understanding of modulating tumor metabolisms for enhanced therapy.

Efficient Sequential Co-Delivery Nanosystem for Inhibition of Tumor and Tumor-Associated Fibroblast-Induced Resistance and Metastasis.

Purpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them. Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier's inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model. Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies. Conclusion: Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.

5- methylcytidine effectively improves spermatogenesis recovery in busulfan-induced oligoasthenospermia mice.

The function and regulatory mechanisms of 5-methylcytidine (m5C) in oligoasthenospermia remain unclear. In this study, we made a mouse model of oligoasthenospermia through the administration of busulfan (BUS). For the first time, we demonstrated that m5C levels decreased in oligoasthenospermia. The m5C levels were upregulated through the treatments of 5-methylcytidine. The testicular morphology and sperm concentrations were improved via upregulating m5C. The cytoskeletal regenerations of testis and sperm were accompanying with m5C treatments. m5C treatments improved T levels and reduced FSH and LH levels. The levels of ROS and MDA were significantly reduced through m5C treatments. RNA sequencing analysis showed m5C treatments increased the expression of genes involved in spermatid differentiation/development and cilium movement. Immunofluorescent staining demonstrated the regeneration of cilium and quantitative PCR (qPCR) confirmed the high expression of genes involved in spermatogenesis. Collectively, our findings suggest that the upregulation of m5C in oligoasthenospermia facilitates testicular morphology recovery and male infertility via multiple pathways, including cytoskeletal regeneration, hormonal levels, attenuating oxidative stress, spermatid differentiation/development and cilium movement. m5C may be a potential therapeutic agent for oligoasthenospermia.

Complexation temperature regulated the structure and digestibility of pea starch-gallic acid complexes during high pressure homogenization.

Formation of starch-polyphenol complexes by high pressure homogenization (HPH) is widely used to reduce starch digestibility and delay the postprandial glycemic response, thereby benefiting obesity and associated metabolic diseases. This study investigated the effect of complexation temperature on multi-scale structures, physicochemical and digestive properties of pea starch-gallic acid (PS-GA) complexes during HPH process, while also elucidating the corresponding molecular mechanism regulating in vitro digestibility. The results demonstrated that elevating complexation temperature from 30 °C to 100 °C promoted the interaction between PS and GA and reached a peak complex index of 9.22 % at 90 °C through non-covalent binding. The enhanced interaction led to the formation of ordered multi-scale structures within PS-GA complexes, characterized by larger particles that exhibited greater thermal stability and elastic properties. Consequently, the PS-GA complexes exhibited substantially reduced digestion rates with the content of resistant starch increased from 28.50 % to 38.26 %. The potential molecular mechanism underlying how complexation temperature regulated digestibility of PS-GA complexes might be attributed to the synergistic effect of the physical barriers from newly ordered structure and inhibitory effect of GA against digestive enzymes. Overall, our findings contribute to the advancement of current knowledge regarding starch-polyphenol interactions and promote the development of functional starches with low postprandial glycemic responses.

MRPS23 is a novel prognostic biomarker and promotes glioma progression.

Mitochondrial ribosomal protein S23 (MRPS23), a component of the ribosome small subunit, has been reported to be overexpressed in various cancers and has been predicted to be involved in increased cell proliferation. It has been confirmed that MRPS23 was involved in the regulation of breast cancer and hepatocellular carcinoma cell proliferation. However, little is known about the function of MRPS23 in glioma. In this study, we found that MRPS23 expression was higher in gliomas than in adjacent normal tissues. Higher expression of MRPS23 in gliomas correlated with poorer prognosis, unfavorable histological features, absence of mutations in the isocitrate dehydrogenase gene (IDH), absence of chromosome 1p and 19q deletions, and responses to chemoradiotherapy. Univariate and multivariate Cox analysis demonstrated MRPS23 expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. KEGG enrichment analysis results indicated that high MRPS23 expression was associated with cell proliferation and immune response-related signaling pathways. We also confirmed that MRPS23 was highly expressed in glioma cells lines, and MRPS23 knockdown significantly reduced cell survival, proliferation, and migration of glioma cells lines. Collectively, these findings offer mechanistic insights into how MRPS23 during glioma progression, and identify MRPS23 as a potential therapeutic target in the future.

Possible quantum-spin-liquid state in van der Waals cluster magnet Nb3Cl8.

The cluster magnet Nb3Cl8consists of Nb3trimmers that form an emergentS= 1/2 two-dimensional triangular layers, which are bonded by weak van der Waals interactions. Recent studies show that its room-temperature electronic state can be well described as a single-band Mott insulator. However, the magnetic ground state is non-magnetic due to a structural transition below about 100 K. Here we show that there exists a thickness threshold below which the structural transition will not happen. For a bulk crystal, a small fraction of the sample maintains the high-temperature structure at low temperatures and such remnant gives rise to linear-temperature dependence of the specific heat at very low temperatures. This is further confirmed by the measurements on ground powder sample orc-axis pressed single crystals, which prohibits the formation of the non-magnetic state. Moreover, the intrinsic magnetic susceptibility also tends to be constant with decreasing temperature. Our results suggest that Nb3Cl8with the high-temperature structure may host a quantum-spin-liquid ground state with spinon Fermi surfaces, which can be achieved by making the thickness of a sample smaller than a certain threshold.

Multifunctional nanoparticles inhibit tumor and tumor-associated macrophages for triple-negative breast cancer therapy.

HYPOTHESIS: Tumor-associated macrophages (TAM) are the mainstay of immunosuppressive cells in the tumor microenvironment, and elimination of M2-type macrophages (M2-TAM) is considered as a potential immunotherapy. However, the interaction of breast cancer cells with macrophages hinders the effectiveness of immunotherapy. In order to improve the efficacy of triple-negative breast cancer (TNBC) therapy, strategies that simultaneously target the elimination of M2-TAM and breast cancer cells may be able to achieve a better therapy. EXPERIMENTS: LyP-SA/AgNP@Dox multifunctional nanoparticles were synthesized by electrostatic adsorption. They were characterized by particle size, potential and spectroscopy. And the efficacy of multifunctional nanoparticles was evaluated in 4 T1 cell lines and M2 macrophages, including their cell uptake intracellular reactive oxygen species (ROS) production and the therapeutic effect. Furthermore, based on the orthotopic xenotransplantation model of triple negative breast cancer, the biological distribution, fluorescence imaging, biosafety evaluation and combined efficacy evaluation of the nanoplatform were performed. FINDINGS: We have successfully prepared LyP-SA/AgNP@Dox and characterized. Administering the nanosystem to 4 T1 tumor cells or M2 macrophages in culture induced accumulation of reactive oxygen species, destruction of mitochondria and apoptosis, and inhibited replication and transcription. Animal experiments demonstrated the nanoparticle had favorable targeting and antitumor activity. Our nanosystem may be useful for simultaneously inhibiting tumor and tumor-associated macrophages in breast cancer and, potentially, other malignancies.

Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy.

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.

High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes.

BACKGROUND: Colorectal cancer is a malignant tumor that poses a serious threat to human health. The main objective of this study is to investigate the mechanism by which Jatrorrhizine (JAT), a root extract from Stephania Epigaea Lo, exerts its anticancer effects in colorectal cancer. METHODS: We initially assessed the inhibitory properties of JAT on SW480 cells using MTT and cell scratch assays. Flow cytometry was employed to detect cell apoptosis. Differentially expressed genes were identified through high-throughput sequencing, and they were subjected to functional enrichment and signaling pathway analysis and PPI network construction. RT-qPCR was used to evaluate gene expression and identify critical differentially expressed genes. Finally, the function and role of differentially expressed genes produced by JAT-treated SW480 cells in colorectal cancer will be further analyzed using the TCGA database. RESULTS: Our study demonstrated that JAT exhibits inhibitory effects on SW480 cells at concentrations of 12.5µM, 25µM, 50µM, and 75µM without inducing cell apoptosis. Through high-throughput sequencing, we identified 244 differentially expressed genes. KEGG and GO analysis of high-throughput sequencing results showed that differentially expressed genes were significantly enriched in MAPK, Wnt, and P53 signaling pathways. Notably, JAT significantly altered the expression of genes associated with ferroptosis. Subsequent RT-qPCR showed that the expression of ferroptosis genes SLC2A3 and ASNS was significantly lower in JAT-treated SW480 cells than in the control group. Analysis by TCGA data also showed that ferroptosis genes SLC2A3 and ASNS were significantly highly expressed in COAD. The prognosis of SLC2A3 was significantly worse in COAD compared to the normal group. SLC2A3 may be a core target of JAT for the treatment of COAD. CONCLUSIONS: JAT can inhibit COAD growth by ferroptosis-related genes. And it is a potential natural substance for the treatment of COAD.

Oral hydrogel nanoemulsion co-delivery system treats inflammatory bowel disease via anti-inflammatory and promoting intestinal mucosa repair.

BACKGROUND: Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon. RESULTS: In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment. CONCLUSIONS: It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.