Matrisomics: Beyond the extracellular matrix for unveiling tumor microenvironment.

The matrisome, a group of proteins constituting or interacting with the extracellular matrix (ECM), has garnered attention as a potent regulator of cancer progression. An increasing number of studies have focused on cancer matrisome utilizing diverse -omics approaches. Here, we present diverse patterns of matrisomal populations within cancer tissues, exploring recent -omics studies spanning different '-omics' levels (epigenomics, genomics, transcriptomics, and proteomics), as well as newly developed sequencing techniques such as single-cell RNA sequencing and spatial transcriptomics. Some matrisome genes showed uniform patterns of upregulated or downregulated expression across various cancers, while others displayed different expression patterns according to the cancer types. This matrisomal dysregulation in cancer was further examined according to their originating cell type and spatial location in the tumor tissue. Experimental studies were also collected to demonstrate the identified roles of matrisome genes during cancer progression. Interestingly, many studies on cancer matrisome have suggested matrisome genes as effective biomarkers in cancer research. Although the specific mechanisms and clinical applications of cancer matrisome have not yet been fully elucidated, recent techniques and analyses on cancer matrisomics have emphasized their biological importance in cancer progression and their clinical implications in deciding the efficacy of cancer treatment.

Healthcare service use and medical outcomes of tracheostomy-dependent children: a nationwide study.

BACKGROUND: Despite the rising trend of tracheostomies in children, there is a lack of comprehensive resources for families to navigate the challenges of living with a tracheostomy, emphasising the need for evidence-based support in understanding postoperative care and long-term adjustments. This study aimed to examine the pattern of using healthcare services and nationwide medical outcomes in children who underwent a tracheotomy before the age of 2 years. METHODS: This retrospective study used the National Health Insurance System database from 2008 to 2016 and included all children codified with tracheotomy procedure codes before their second birthday. Healthcare utilisation, such as medical costs, number of hospital visits, home healthcare nursing and medical diagnoses on readmission, in the first 2 years after tracheotomy was evaluated. Multivariable logistic regression analysis was used to determine the factors affecting mortality. RESULTS: In total, 813 patients were included in this study. Their use of healthcare services and the accompanying expenses were higher than the national medians for similar age groups; however, both metrics decreased in the second year. The major causes of admission within 2 years of surgery were respiratory and neurological diseases. The mortality rate within 2 years was 37.8%. Higher risks of mortality were associated with having two or more complex chronic conditions. Use of home healthcare nursing services was associated with a lower mortality risk. CONCLUSION: Paediatric patients with more complex chronic conditions tended to have higher mortality rates within 2 years after surgery. However, receiving home healthcare nursing was significantly associated with a reduced risk of death. Many causes of hospitalisation may be preventable with education and supportive care. Therefore, further research for establishing an integrated care system for these patients and their caregivers is required.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single-cell RNA sequencing (scRNA-seq) data, it is founded that NAMPT is highly expressed in SPP1+ tumor-associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity. A NAMPThigh gene signature in SPP1+ TAMs correlated with worse prognostic outcomes in CRC patients. The effect of Nampt deletion in the myeloid compartment of mice during CRC development is explored. NAMPT deficiency in macrophages resulted in HIF-1α destabilization, leading to reduction in M2-like TAM polarization. NAMPT deficiency caused significant decreases in the efferocytosis activity of macrophages, which enhanced STING signaling and the induction of type I IFN-response genes. Expression of these genes contributed to anti-tumoral immunity via potentiation of cytotoxic T cell activity in the TME. Overall, these findings suggest that NAMPT-initiated TAM-specific genes can be useful in predicting poor CRC patient outcomes; strategies aimed at targeting NAMPT may provide a promising therapeutic approach for building an immunostimulatory TME in CRC progression.

Treatment of primary sclerosing cholangitis combined with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a progressive cholestatic, inflammatory, and fibrotic disease that is strongly associated with inflammatory bowel disease (IBD). PSC-IBD represents a unique disease entity and patients with this disease have an increased risk of malignancy development, such as colorectal cancer and cholangiocarcinoma. The pathogenesis of PSC-IBD involves genetic and environmental factors such as gut dysbiosis and bile acids alteration. However, despite the advancement of disease characteristics, no effective medical therapy has proven to have a significant impact on the prognosis of PSC. The treatment options for patients with PSC-IBD do not differ from those for patients with PSC alone. Potential candidate drugs have been developed based on the pathogenesis of PSC-IBD, such as those that target modulation of bile acids, inflammation, fibrosis, and gut dysbiosis. In this review, we summarize the current medical treatments for PSC-IBD and the status of new emerging therapeutic agents.

Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis.

The close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) provides a good opportunity to comprehend the gut-liver axis. The gut and the liver have reciprocal interactions, including how gut inflammation influences the liver through immune cells and the microbiota and how the microbiota in the gut modifies bile acids, which are produced and secreted from the liver. PSC-IBD shows distinct clinical findings from classical IBD. In addition, a distinct genetic predisposition and unique microbiota composition suggest that PSC-IBD is an independent disease entity. Understanding the pathogenesis of PSC-IBD helps to develop novel and effective therapeutic agents. Given the high risk of malignancies associated with PSC-IBD, it is critical to identify patients at high risk and implement appropriate surveillance and monitoring strategies. In this review, we provide an overview of PSC-IBD, which exemplifies the gut-liver axis.

Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity.

Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.

Clinical Characteristics of Korean Patients with Elderly-Onset Crohn's Disease: Results from the Prospective CONNECT Study.

The clinical course and prognosis of patients with elderly-onset Crohn's disease (CD) remain unclear. This study aimed to analyze the clinical characteristics and outcomes of elderly-onset CD patients from the prospective CONNECT study cohort, a nationwide, multicenter cohort study of patients with CD in Korea. Among a total of 1,175 patients in the prospective CONNECT study cohort, 94 patients (Montreal age A3) were included and divided into two groups according to their age at diagnosis: the elderly-onset group (diagnosed with CD after 60 years of age, n=26, 67.54±6.7 years) and late adult-onset group (diagnosed as CD at age 41 to 59 years, n=68, 48.06±5.1 years). The elderly-onset group was characterized by a lower Crohn's disease activity index at diagnosis (124.89±101.9 vs 189.55±128.6, p=0.023) and higher rates of previous anti-tuberculosis treatment (34.6% vs 4.4%, p<0.001) than the late adult-onset group. Compared with the late adult-onset group, the elderly-onset group showed a significantly less use of thiopurines (p=0.003), as well as anti-tumor necrosis factor-alpha agents (p=0.047). Additionally, the elderly-onset group was less likely to require bowel resection than the late adult-onset group (p=0.067), suggesting that elderly-onset CD patients in Korea appear to have more favorable clinical outcomes than late adult-onset CD patients.

LCK-Mediated RIPK3 Activation Controls Double-Positive Thymocyte Proliferation and Restrains Thymic Lymphoma by Regulating the PP2A-ERK Axis.

Receptor-interacting protein kinase 3 (RIPK3) is the primary regulator of necroptotic cell death. RIPK3 expression is often silenced in various cancer cells, which suggests that it may have tumor suppressor properties. However, the exact mechanism by which RIPK3 negatively regulates cancer development and progression remains unclear. This report indicates that RIPK3 acts as a potent regulator of the homeostatic proliferation of CD4+ CD8+ double-positive (DP) thymocytes. Abnormal proliferation of RIPK3-deficient DP thymocytes occurs independently of the well-known role for RIPK3 in necroptosis (upstream of MLKL activation), and is associated with an incidental thymic mass, likely thymic hyperplasia. In addition, Ripk3-null mice develop increased thymic tumor formation accompanied by reduced host survival in the context of an N-ethyl-N-nitrosourea (ENU)-induced tumor model. Moreover, RIPK3 deficiency in p53-null mice promotes thymic lymphoma development via upregulated extracellular signal-regulated kinase (ERK) signaling, which correlates with markedly reduced survival rates. Mechanistically, lymphocyte-specific protein tyrosine kinase (LCK) activates RIPK3, which in turn leads to increases in the phosphatase activity of protein phosphatase 2 (PP2A), thereby suppressing hyper-activation of ERK in DP thymocytes. Overall, these findings suggest that a RIPK3-PP2A-ERK signaling axis regulates DP thymocyte homeostasis and may provide a potential therapeutic target to improve thymic lymphoma therapies.

Management of inflammatory bowel disease beyond tumor necrosis factor inhibitors: novel biologics and small-molecule drugs.

The incidence and prevalence of inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, have increased in Asia and developing countries. In the past two decades, anti-tumor necrosis factor (TNF) agents have revolutionized the treatment of IBD, in part by decreasing the rates of complications and surgery. Although anti-TNF agents have changed the course of IBD, there are unmet needs in terms of primary and secondary non-responses and side effects such as infections and malignancies. Novel biologics and small-molecule drugs have been developed for IBD, and the medical treatment options have improved. These drugs include sphingosine-1-phosphate receptor modulators and anti-integrins to block immune cell migration, and cytokine and Janus kinase inhibitors to block immune cell communications. In this review, we discuss the approved novel biologics and small-molecule drugs, including several of those in the late stages of development, for the treatment of IBD.

Clinical implications of discrepancies in predicting pediatric mortality between Pediatric Index of Mortality 3 and Pediatric Logistic Organ Dysfunction-2.

BACKGROUND: Pediatric Index of Mortality 3 (PIM 3) and Pediatric Logistic Organ Dysfunction-2 (PELOD-2) are validated tools for predicting mortality in children. Research suggests that these tools may have different predictive performance depending on patient group characteristics. Therefore, we designed this study to identify the factors that make the mortality rates predicted by the tools different. METHODS: This retrospective study included patients (<18 years) who were admitted to a pediatric intensive care unit from July 2017 to May 2019. After defining the predicted mortality of PIM 3 minus the predicted mortality rate of PELOD-2 as "difference in mortality prediction," the clinical characteristics significantly related to this were analyzed using multivariable regression analysis. Predictive performance was analyzed through the Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUROC). RESULTS: In total, 945 patients (median [interquartile range] age, 3.0 [0.0-8.0] years; girls, 44.7%) were analyzed. The Hosmer-Lemeshow test revealed AUROCs of 0.889 (χ2=10.187, P=0.313) and 0.731 (χ2=6.220, P=0.183) of PIM 3 and PELOD-2, respectively. Multivariable linear regression analysis revealed that oxygen saturation, partial pressure of CO2, base excess, platelet counts, and blood urea nitrogen levels were significant factors. Patient condition-related factors such as cardiac bypass surgery, seizures, cardiomyopathy or myocarditis, necrotizing enterocolitis, cardiac arrest, leukemia or lymphoma after the first induction, bone marrow transplantation, and liver failure were significantly related (P<0.001). CONCLUSIONS: Both tools predicted observed mortality well; however, caution is needed in interpretation as they may show different prediction results in relation to specific clinical characteristics.

Comparison of Two Types of 1-L Polyethylene Glycol-ascorbic Acid as Colonoscopic Bowel Preparation: A Prospective Randomized Study.

Background/Aims: Recently, 1-L polyethylene glycol-ascorbic acid (PEG-Asc) has been used to reduce the volume of preparation agents in colonoscopy. This clinical trial aimed to compare the efficacy and safety of two types of 1-L PEG-Asc (CleanViewAL® [Tae Joon Pharmaceutical Company, Seoul, Korea] and Plenvu® [Norgine, Harefield, United Kingdom]) in average-aged adults. Methods: This study was a prospective, randomized, non-inferiority, open-label, phase 4 clinical trial. The primary endpoint was the efficacy evaluated using the Boston bowel preparation scale (BBPS), and the secondary endpoint was clinical safety. Results: In total, 173 patients were assigned to either the CleanViewAL® (n=84) or Plenvu® (n=89) group. Overall cleansing successes of 97.6% (82/84) and 98.8% (88/89) were achieved in the CleanViewAL® group and in the Plenvu® group, respectively, showing that CleanViewAL® has similar bowel cleansing efficacy to Plenvu® (95% CI, -0.052 to 0.027; p=0.207). The total BBPS score was 8.67±1.00 and 8.70±0.76 in the CleanViewAL® group and Plenvu® group, respectively (p=0.869). The most common adverse symptom was nausea, and no adverse symptoms requiring hospitalization were reported in either group. There were no cases of critical hypernatremia and liver dysfunction exceeding the common terminology criteria for adverse events grade I. An overall satisfaction score (scale of 1 to 10) showed no difference between the two groups (p=0.289). However, the CleanViewAL® group showed a higher taste satisfaction score (scale of 1 to 5) than the Plenvu® group (CleanViewAL®: 2.90±0.91, Plenvu®: 2.60±0.86, p=0.028). Conclusions: Both types of 1-L PEG-Asc, CleanViewAL® and Plenvu®, are effective and safe bowel cleansing agents in average-aged adults. CleanViewAL® was preferred in terms of taste satisfaction.

[Diagnosis and Treatment of Colonic Diverticular Disease].

Colonic diverticulosis is one of the most common conditions of the digestive system and patients generally remain asymptomatic. However, about 20% of patients develop symptomatic diverticular disease such as acute diverticulitis or diverticular hemorrhage, and these have become a huge burden on healthcare systems worldwide. Recent understanding of the pathophysiology of diverticulosis and diverticular disease suggests the role of multiple factors including genetic and environment. Based on this understanding, a preventive strategy to reduce the risk factors of diverticulosis and diverticular disease is highly recommended. The diagnosis of the acute diverticulitis relies on imaging modalities such as an abdominal-pelvic CT scan together with symptoms and signs. Treatment of diverticular disease should be individualized and include modification of lifestyle, use of antibiotics, and surgery. Recent guidelines recommend pursuing less aggressive treatment for patients with acute diverticulitis. This review will provide an overview of both the existing and evolving understanding regarding colonic diverticulosis and diverticular disease and can help clinicians in the management of their patients with diverticular disease.

miR-4742-5p promotes invasiveness of gastric cancer via targeting Rab43: An in vitro study.

miRNA (miR)-4742-5p is a recently identified microRNA regarding progression and metastasis in gastric cancer (GC). However, the biological function of this novel miRNA is largely unknown. We identified that the miR-4742-5p expression level was variably increased in GC cell lines. Suppression of miR-4742-5p using miR-inhibitor reduced the proliferation, migration, and invasion of GC cells with high miR-4742-5p expression, whereas overexpression of miR-4742-5p-mimic enhanced the aforementioned properties in GC cells with low miR-4742-5p expression. miR-4742-5p expression induced the decreases of Zo-1 and E-cadherin expression as well as the increases of vimentin and N-cadherin expression, leading to epithelial-mesenchymal transition (EMT) of cancer cells. RNA sequencing results indicated Ras-related GTP-binding protein 43 (Rab43) as a potential target gene. We identified that the expression of Rab43 is associated with activation of AKT and nuclear factor-kappa B (NF-κB) which are key oncogenic pathways in cancer cells. Our results demonstrate a new component in GC progression, promising a potential therapeutic strategy.

Clinical Features and Long-term Prognosis of Crohn's Disease in Korea: Results from the Prospective CONNECT Study.

Background/Aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions: The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages.

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway and plays a crucial role in the maintenance of the NAD+ pool during inflammation. Considering that macrophages are essential for tissue homeostasis and inflammation, we sought to examine the functional impact of NAMPT in inflammatory macrophages, particularly in the context of inflammatory bowel disease (IBD). In this study, we show that mice with NAMPT deletion within the myeloid compartment (Namptf/fLysMCre+/-, Nampt mKO) have more pronounced colitis with lower survival rates, as well as numerous uncleared apoptotic corpses within the mucosal layer. Nampt-deficient macrophages exhibit reduced phagocytic activity due to insufficient NAD+ abundance, which is required to produce NADPH for the oxidative burst. Nicotinamide mononucleotide (NMN) treatment rescues NADPH levels in Nampt mKO macrophages and sustains superoxide generation via NADPH oxidase. Consequently, Nampt mKO mice fail to clear dead cells during tissue repair, leading to substantially prolonged chronic colitis. Moreover, systemic administration of NMN, to supply NAD+, effectively suppresses the disease severity of DSS-induced colitis. Collectively, our findings suggest that activation of the NAMPT-dependent NAD+ biosynthetic pathway, via NMN administration, is a potential therapeutic strategy for managing inflammatory diseases.