Current evidence and therapeutic implication of PANoptosis in cancer.

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cancer cells and influencing treatment outcomes. The application of RCD in cancer treatment is marked by its potential in targeted therapy and immunotherapy. As a type of RCD, PANoptosis has emerged as a unique form of programmed cell death (PCD) characterized by features of pyroptosis, apoptosis, and necroptosis but cannot be fully explained by any of these pathways alone. It is regulated by a multi-protein complex called the PANoptosome. As a relatively new concept first described in 2019, PANoptosis has been shown to play a role in many diseases, including cancer, infection, and inflammation. This study reviews the application of PCD in cancer, particularly the emergence and implication of PANoptosis in developing therapeutic strategies for cancer. Studies have shown that the characterization of PANoptosis patterns in cancer can predict survival and response to immunotherapy and chemotherapy, highlighting the potential for PANoptosis to be used as a therapeutic target in cancer treatment. It also plays a role in limiting the spread of cancer cells. PANoptosis allows for the elimination of cancer cells by multiple cell death pathways and has the potential to address various challenges in cancer treatment, including drug resistance and immune evasion. Moreover, active investigation of the mechanisms and potential therapeutic agents that can induce PANoptosis in cancer cells is likely to yield effective cancer treatments and improve patient outcomes. Research on PANoptosis is still ongoing, but it is a rapidly evolving field with the potential to lead to new treatments for various diseases, including cancer.

Role of glycolysis in inflammatory bowel disease and its associated colorectal cancer.

Inflammatory bowel disease (IBD) has been referred to as the "green cancer," and its progression to colorectal cancer (CRC) poses a significant challenge for the medical community. A common factor in their development is glycolysis, a crucial metabolic mechanism of living organisms, which is also involved in other diseases. In IBD, glycolysis affects gastrointestinal components such as the intestinal microbiota, mucosal barrier function, and the immune system, including macrophages, dendritic cells, T cells, and neutrophils, while in CRC, it is linked to various pathways, such as phosphatidylinositol-3-kinase (PI3K)/AKT, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and transcription factors such as p53, Hypoxia-inducible factor (HIF), and c-Myc. Thus, a comprehensive study of glycolysis is essential for a better understanding of the pathogenesis and therapeutic targets of both IBD and CRC. This paper reviews the role of glycolysis in diseases, particularly IBD and CRC, via its effects on the intestinal microbiota, immunity, barrier integrity, signaling pathways, transcription factors and some therapeutic strategies targeting glycolytic enzymes.

Resveratrol alleviates DSS-induced IBD in mice by regulating the intestinal microbiota-macrophage-arginine metabolism axis.

BACKGROUND: Inflammatory bowel disease (IBD) is a global disease with a growing public health concern and is associated with a complex interplay of factors, including the microbiota and immune system. Resveratrol, a natural anti-inflammatory and antioxidant agent, is known to relieve IBD but the mechanism involved is largely unexplored. METHODS: This study examines the modulatory effect of resveratrol on intestinal immunity, microbiota, metabolites, and related functions and pathways in the BALB/c mice model of IBD. Mouse RAW264.7 macrophage cell line was used to further explore the involvement of the macrophage-arginine metabolism axis. The treatment outcome was assessed through qRT-PCR, western blot, immunofluorescence, immunohistochemistry, and fecal 16S rDNA sequencing and UHPLC/Q-TOF-MS. RESULTS: Results showed that resveratrol treatment significantly reduced disease activity index (DAI), retained mice weight, repaired colon and spleen tissues, upregulated IL-10 and the tight junction proteins Occludin and Claudin 1, and decreased pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. Resveratrol reduced the number of dysregulated metabolites and improved the gut microbial community structure and diversity, including reversing changes in the phyla Bacteroidetes, Proteobacteria, and Firmicutes, increasing 'beneficial' genera, and decreasing potential pathogens such as Lachnoclostridium, Acinobacter, and Serratia. Arginine-proline metabolism was significantly different between the colitis-treated and untreated groups. In the colon mucosa and RAW264.7 macrophage, resveratrol regulated arginine metabolism towards colon protection by increasing Arg1 and Slc6a8 and decreasing iNOS. CONCLUSION: This uncovers a previously unknown mechanism of resveratrol treatment in IBD and provides the microbiota-macrophage-arginine metabolism axis as a potential therapeutic target for intestinal inflammation.

The role of mesenchymal stem cell-derived exosome in epigenetic modifications in inflammatory diseases.

Epigenetic modification is a complex process of reversible and heritable alterations in gene function, and the combination of epigenetic and metabolic alterations is recognized as an important causative factor in diseases such as inflammatory bowel disease (IBD), osteoarthritis (OA), systemic lupus erythematosus (SLE), and even tumors. Mesenchymal stem cell (MSC) and MSC-derived exosome (MSC-EXO) are widely studied in the treatment of inflammatory diseases, where they appear to be promising therapeutic agents, partly through the potent regulation of epigenetic modifications such as DNA methylation, acetylation, phosphorylation, and expression of regulatory non-coding RNAs, which affects the occurrence and development of inflammatory diseases. In this review, we summarize the current research on the role of MSC-EXO in inflammatory diseases through their modulation of epigenetic modifications and discuss its potential application in the treatment of inflammatory diseases.

Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review).

Ferroptosis, a novel form of regulated cell death, is characterized by the accumulation of labile iron and lipid peroxidation, and the excessive production of reactive oxygen species (ROS). Although ferroptosis lies at the center of crucial biological activities involving O2, iron and polyunsaturated fatty acids (PUFAs), which are essential for cell proliferation and growth, the interaction between these molecules could also mediate the accumulation of toxic levels of ROS and lipid peroxides, which can then cause damage to cellular membranes and ultimately result in cell death. Recent reports have indicated that ferroptosis participates in the development and progression of inflammatory bowel disease (IBD), offering a new exploratory field which may aid in the more in­depth understanding of the pathogenesis and therapeutic targets of IBD. Of note, the mitigation of the characteristic features of ferroptosis, such as depleted glutathione (GSH) levels, inactivated glutathione peroxidase 4 (GPX4), elevated levels of lipid peroxidation and iron overload significantly relieve IBD. This has attracted the attention of researches aiming to examine therapeutic agents that inhibit ferroptosis in IBD, including radical­trapping antioxidants, enzyme inhibitors, iron chelators, protein degradation inhibitors, stem cell­derived exosomes and oral N­acetylcysteine or glutathione. The present review summarizes and discusses the current data that implicate ferroptosis in the pathogenesis of IBD and its inhibition as a novel alternate therapeutic target for IBD. The mechanisms and key mediators of ferroptosis, including GSH/GPX4, PUFAs, iron and organic peroxides are also discussed. Although the field is relatively new, the therapeutic regulation of ferroptosis has exhibited promising outcomes as a novel treatment avenue for IBD.

The effect of students' online learning experience on their satisfaction during the COVID-19 pandemic: The mediating role of preference.

Introduction: During the peak of the COVID-19 pandemic, nearly all educational institutions globally had to eventually embrace the maneuver of transferring to nearly 100% online learning as a new routine for different curricula. Although many students in developing countries such as Kenya are only experiencing the exclusive online learning approach for the first time, research on students' experience and satisfaction with COVID-19-imposed online learning is largely lacking. Thus, this study examined the effect of online-learning experiences on satisfaction in the setting of the COVID-19 pandemic in Kenya. The mediating role of students' preference on the relationship between online-learning experience and satisfaction was also examined. Methods: A web-based survey involving 501 respondents was analyzed using IBM® SPSS® and AMOS software platforms. A structural equation model (SEM) was used to analyze the relationships. Results and Discussion: Results showed that 80% of participants indicated their preference for in-person learning as against 20% for online learning. Students' satisfaction-SS had a significant positive correlation with online classroom perceived quality-OCPQ, acquisition of self-confidence-ASC, teaching performance and engagement-TPE, and preference for online learning-POL but a negative correlation with internet access and cost-IAC. Moreover, while POL positively correlated with OCPQ, ASC, and TPE, it negatively correlated with IAC. Both the structural model for the main effect and the mediation model provided a good fit and confirmed these relationships. Student preference had a significant effect on satisfaction and played a significant mediating role in the relationship between online-learning experience and satisfaction. These findings shed light on the underlying factors that explain students' online learning satisfaction and provide guidelines for universities and policymakers to make better decisions that enhance students' online-learning experience and satisfaction.

hucMSC-Ex Alleviates IBD-Associated Intestinal Fibrosis by Inhibiting ERK Phosphorylation in Intestinal Fibroblasts.

Background: Intestinal fibrosis, one of the complications of inflammatory bowel disease (IBD), is associated with fistula and intestinal stricture formation. There are currently no treatments for fibrosis. Mesenchymal stem cell-derived exosomes have been proven to exert inhibitory and reversal effects in IBD and other organ fibrosis. In this study, we explored the role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) in IBD-related fibrosis and its associated mechanism to provide new ideas for the prevention and treatment of IBD-related intestinal fibrosis. Methods: We established a DSS-induced mouse IBD-related intestinal fibrosis model and observed the effect of hucMSC-Ex on the mouse model. We also used the TGF-induced human intestinal fibroblast CCD-18Co to observe the role of hucMSC-Ex in the proliferation, migration, and activation of intestinal fibroblasts. Having observed that the extracellular-signal-regulated kinase (ERK) pathway in intestinal fibrosis can be inhibited by hucMSC-Ex, we treated intestinal fibroblasts with an ERK inhibitor to emphasize the potential target of ERK phosphorylation in the treatment of IBD-associated intestinal fibrosis. Results: In the animal model of IBD-related fibrosis, hucMSC-Ex alleviated inflammation-related fibrosis as evident in the thinning of the mice's intestinal wall and decreased expression of related molecules. Moreover, hucMSC-Ex inhibited TGF-ß-induced proliferation, migration, and activation of human intestinal fibroblasts, and ERK phosphorylation played a key role in IBD-associated fibrosis. The inhibition of ERK decreased the expression of fibrosis-related indicators such as α-SMA, fibronectin, and collagen I. Conclusion: hucMSC-Ex alleviates DSS-induced IBD-related intestinal fibrosis by inhibiting profibrotic molecules and intestinal fibroblast proliferation and migration by decreasing ERK phosphorylation.

Exosome-mediated macrophage regulation for inflammatory bowel disease repair: a potential target of gut inflammation.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex condition without a definite cause. During IBD, immune cells such as macrophages release proinflammatory cytokines and chemokines, contributing to intestinal barrier integrity dysfunction. IBD is largely influenced by macrophages, which are classified into subtypes M1 and M2. M1 macrophages have been found to contribute to the development of IBD, whereas M2 macrophages alleviate IBD. Hence, agents that cause increased polarization of the M2 phenotype could help repair IBD. Exosomes, as ubiquitous conveyors of intercellular messages, are involved in immune responses and immune-mediated disease processes. Exosomes and their microRNA (miRNA) from healthy cells have been found to polarize macrophages to M2 to repair IBD due to their anti-inflammatory properties; however, those from inflammatory-driven cells and disease cells promote M1 macrophages to perpetuate IBD. Here, we review the biogenesis, biochemical composition, and sources of exosomes, as well as the roles of exosomes as extracellular vesicles in regulation of macrophages to repair IBD.

The role of NOD2 in intestinal immune response and microbiota modulation: A therapeutic target in inflammatory bowel disease.

As an intracellular pattern recognition receptor (PPR), the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) triggers a cascade of immune responses. Previous studies of NOD2 regarding inflammatory bowel disease (IBD) mainly focused on the relevance of NOD2 mutations and loss within the disease onset and progression. With increasing research, more studies are exploring other functional roles and clinical applications of NOD2. In this review, we discuss the role of NOD2 in intestinal immune response and microbiota modulation in IBD and explore its clinical potential as a therapeutic target for IBD.

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion.

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial-mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.

Mesenchymal stem cell-derived exosome mitigates colitis via the modulation of the gut metagenomics-metabolomics-farnesoid X receptor axis.

Inflammatory bowel disease (IBD) is associated with chronic gut immune dysregulation and altered microbiome and metabolite composition. Bile acids and their receptors such as the farnesoid X receptor (FXR) form a crucial component of the chemical communications between the intestinal microbiota and the host immune system; thus, alterations in the bile acid pool affect intestinal homeostasis and exacerbate IBD. Considering the promising therapeutic effect of mesenchymal stem cell-derived exosomes (MSC-Ex) on IBD, this study assessed the regulatory effect of MSC-Ex on the gut bacteria composition and diversity, metabolites, and their related functions and pathways, as well as key inflammatory and anti-inflammatory cytokines during the mitigation of IBD. The dextran sulfate sodium (DSS)-induced IBD model of BABL/C mice was established, consisting of three groups: control, DSS, and MSC-Ex groups. Post administration of MSC-Ex, the effect was evaluated via hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), qRT-PCR, and western blotting. Mice fecal samples were obtained for metagenomics and metabolomics analysis via 16S rRNA gene sequencing and UHPLC/Q-TOF-MS respectively. Results showed that MSC-Ex mitigated colitis by significantly relieving the macroscopic and microscopic features of inflammation, modulating the gut metagenomics and metabolomics profile, and increasing colonic FXR. MSC-Ex improved the gut microbiota composition by significantly restoring the structure of OTUs and colitis-induced reduction in α-diversity, increasing the abundance of 'healthy' bacteria, decreasing disease-associated bacteria, decreasing detrimental functions, and enhancing other vital cellular functions. For the first time, we demonstrate that MSC-Ex mitigates colitis in mice by modulating the gut metagenomics-metabolomics-FXR axis, thus providing potential therapeutic targets.

The gut metagenomics and metabolomics signature in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), a chronic gut immune dysregulation and dysbiosis condition is rapidly increasing in global incidence. Regardless, there is a lack of ideal diagnostic markers, while conventional treatment provides scarce desired results, thus, the exploration for better options. Changes in the gut microbial composition and metabolites either lead to or are caused by the immune dysregulation that characterizes IBD. This study examined the fecal metagenomics and metabolomic changes in IBD patients. A total of 30 fecal samples were collected from 15 IBD patients and 15 healthy controls for 16S rDNA gene sequencing and UHPLC/Q-TOF-MS detection of metabolomics. Results showed that there was a severe perturbation of gut bacteria community composition, diversity, metabolites, and associated functions and metabolic pathways in IBD. This included a significantly decreased abundance of Bacteroidetes and Firmicutes, increased disease-associated phyla such as Proteobacteria and Actinobacteria, and increased Escherichia coli and Klebsiella pneumoniae in IBD. A total of 3146 metabolites were detected out of which 135 were differentially expressed between IBD and controls. Metabolites with high sensitivity and specificity in differentiating IBD from healthy individuals included 6,7,4'-trihydroxyisoflavone and thyroxine 4'-o-.beta.-d-glucuronide (AUC = 0.92), normorphine and salvinorin a (AUC = 0.90), and trichostachine (AUC = 0.91). Moreover, the IBD group had significantly affected pathways including primary bile acid biosynthesis, vitamin digestion and absorption, and carbohydrate metabolism. This study reveals that the combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and IBD patients and consequently serve as therapeutic and diagnostic targets.

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway.

As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.

Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy.

Intestinal fibrosis is an important complication of inflammatory bowel disease (IBD). In the course of the development of fibrosis, certain parts of the intestine become narrowed, significantly destroying the structure and function of the intestine and affecting the quality of life of patients. Chronic inflammation is an important initiating factor of fibrosis. Unfortunately, the existing anti-inflammatory drugs cannot effectively prevent and alleviate fibrosis, and there is no effective anti-fibrotic drug, which makes surgical treatment the mainstream treatment for intestinal fibrosis and stenosis. Mesenchymal stem cells (MSCs) are capable of tissue regeneration and repair through their self-differentiation, secretion of cytokines, and secretion of extracellular vesicles. MSCs have been shown to play an important therapeutic role in the fibrosis of many organs. However, the role of MSC in intestinal fibrosis largely remained unexplored. This review summarizes the mechanism of intestinal fibrosis, including the role of immune cells, TGF-ß, and the gut microbiome and metabolites. Available treatment options for fibrosis, particularly, MSCs are also discussed.

Research on natural products from traditional Chinese medicine in the treatment of myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a complicated pathologic process that involves multiple factors including oxidative stress (free radical damage), inflammatory response, calcium overloading, and apoptosis in cardiomyocytes. According to Traditional Chinese Medicine (TCM), MIRI belongs to the categories of "chest numbness", "palpitations" and "angina pectoris". Present data indicate that the application of TCM in myocardial ischemia-reperfusion injury is promising and continues to attract research attention. While the efficacy of Chinese herbal medicine has been well-proven, the underlying molecular mechanisms remain elusive. The common proven mechanisms of Chinese herbal medicine in the treatment of MIRI include regulating lipid metabolism, protecting mitochondria, and improving energy metabolism, attenuating calcium (Ca2+) overload, scavenging oxygen free radicals, inhibiting apoptosis, and reducing autophagy. Others are the regulation of inflammatory cytokine expressions and healing of inflammatory lesions, modulation of cell signaling pathways, improvement of endothelial cell function, and protection of myocardial cells. In this review, we highlight recent studies that focus on elucidating these molecular mechanisms and the therapeutic effects of natural compounds deriving from TCM in MIRI, to ascertain the research progress made and the prospects in this field.

Emerging role of protein modification in inflammatory bowel disease.

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-|κB (NF-|κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1ß (IL-||1ß), tumor necrosis factor-α (TNF|-|α), and interferon-|γ (IFN-|γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.

hucMSC-Derived Exosomes Alleviate the Deterioration of Colitis via the miR-146a/SUMO1 Axis.

Human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Ex) plays an important role in tissue repair and immunomodulation, leading to the mitigation of inflammatory bowel disease. However, the preventive function of hucMSC-Ex in the onset and progression of colitis-associated colon cancer (CAC) is poorly understood. In the current study, dextran sodium sulfate/azoxymethane-induced colitis mouse model was established, and the mice disease activity index, body weight, colon length, tumor counts, survival curve, tissue H&E/immunohistochemistry, and cytokines expression were analyzed to evaluate the effects of hucMSC-Ex on CAC. In addition, miR-146a mimics were transfected into colonic epithelial cells (fetal human cells) to evaluate their role in the hucMSC-Ex-mediated regulation of SUMO1. The results showed that hucMSC-Ex inhibits the expression of SUMO1 to reduce the process of CAC progression. Further analysis indicated that miR-146a targets and inhibits SUMO1 expression and its binding to ß-catenin. In conclusion, our findings showed that hucMSC-Ex is effective in alleviating the deterioration of colitis via the miR-146a-mediated inhibition of SUMO1, which is crucial in this disease process.

Mucin-Type O-Glycans: Barrier, Microbiota, and Immune Anchors in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which affects about 7 million people globally, is a chronic inflammatory condition of the gastrointestinal tract caused by gut microbiota alterations, immune dysregulation, and genetic and environmental factors. The association of microbial and immune molecules with mucin-type O-glycans has been increasingly noticed by researchers. Mucin is the main component of mucus, which forms a protective barrier between the microbiota and immune cells in the colon. Mucin-type O-glycans alter the diversity of gastrointestinal microorganisms, which in turn increases the level of O-glycosylation of host intestinal proteins via the utilization of glycans. Additionally, alterations in mucin-type O-glycans not only increase the activity and stability of immune cells but are also involved in the maintenance of intestinal mucosal immune tolerance. Although there is accumulating evidence indicating that mucin-type O-glycans play an important role in IBD, there is limited literature that integrates available data to present a complete picture of exactly how O-glycans affect IBD. This review emphasizes the roles of the mucin-type O-glycans in IBD. This seeks to provide a better understanding and encourages future studies on IBD glycosylation and the design of novel glycan-inspired therapies for IBD.

The Effects of Mesenchymal Stem Cell on Colorectal Cancer.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract with nonobvious early symptoms and late symptoms of anemia, weight loss, and other systemic symptoms. Its morbidity and fatality rate are next only to gastric cancer, esophageal cancer, and primary liver cancer among digestive malignancies. In addition to the conventional surgical intervention, other therapies such as radiotherapy and chemotherapy and new treatment methods such as biologics and microbiological products have been introduced. As a promising cell therapy, mesenchymal stem cell (MSC) has attracted extensive research attention. MSCs are early undifferentiated pluripotent stem cells, which have the common features of stem cells, including self-replication, self-division, self-renewal, and multidirectional differentiation. MSCs come from a wide range of sources and can be extracted from a variety of tissues such as the bone marrow, umbilical cord, and fat. Current studies have shown that MSCs have a variety of biological functions such as immune regulation, tissue damage repair, and therapeutic effects on tumors such as CRC. This review outlines the overview of MSCs and CRC and summarizes the role of MSC application in CRC.

hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis.

BACKGROUND: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. METHODS: In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. RESULTS: hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1ß, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. CONCLUSION: hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.