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Inflammation is an essential component of the immune response that protects the host against pathogens and facilitates tissue repair. Chronic inflammation is a critical factor in cancer development and progression. It affects every stage of tumor development, from initiation and promotion to invasion and metastasis. Tumors often create an inflammatory microenvironment that induces angiogenesis, immune suppression, and malignant growth. Immune cells within the tumor microenvironment interact actively with cancer cells, which drives progression through complex molecular mechanisms. Chronic inflammation is triggered by factors such as infections, obesity, and environmental toxins and is strongly linked to increased cancer risk. However, acute inflammatory responses can sometimes boost antitumor immunity; thus, inflammation presents both challenges and opportunities for therapeutic intervention. This review examines how inflammation contributes to tumor biology, emphasizing its dual role as a critical factor in tumorigenesis and as a potential therapeutic target.

Interleukin-33 (IL-33), IL-36, and IL-38 are members of the IL-1 cytokine family. The expression of each cytokine has been reported to be increased in the inflamed mucosa of patients with inflammatory bowel disease (IBD). IL-33 and IL-36 have been studied for pro- and anti-inflammatory functions, and IL-38 has been characterized as an anti-inflammatory cytokine by antagonizing the IL-36 receptor (IL-36R). IL-33 is a nuclear cytokine constitutively expressed by certain cell types such as epithelial, endothelial, and fibroblast-like cells and released on necrotic cell death. IL-33 mainly induces type 2 immune response through its receptor suppression tumorigenicity 2 (ST2) from Th2 cells and type 2 innate lymphoid cells (ILC2s), but also by stimulating Th1 cells, regulatory T cells, and CD8+ T cells. IL-36 cytokines consist of three agonists: IL-36α, IL-36β, and IL-36γ, and two receptor antagonists: IL-36R antagonist (IL-36Ra) and IL-38. All IL-36 cytokines bind to the IL-36R complex and exert various functions through NF-κB and mitogen-activated protein kinase (MAPK) pathways in inflammatory settings. IL-33 and IL-36 also play a crucial role in intestinal fibrosis characteristic manifestation of CD. In this review, we focused on the current understanding of the pro- and anti-inflammatory roles of IL-33, IL-36, and IL38 in experimental colitis and IBD patients.

BackgroundThe mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples.MethodsA total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn’s disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing.ResultsThere were no significant differences in microbial structure among different anatomical sites (the ileum, cecum and sigmoid colon) within individuals. There was, however, a significant difference in microbial structure between CD, UC and non-IBD controls. The difference between CD and non-IBD controls was more marked than that between UC patients and non-IBD controls. α-Diversity was significantly lower in UC and CD patients than non-IBD controls. When comparing CD patients with non-IBD controls, the phylum Proteobacteria was significantly increased and the phyla Firmicutes and Bacteroidetes were significantly reduced. These included a significant increase in the genera Escherichia, Ruminococcus (R. gnavus), Cetobacterium, Actinobacillus and Enterococcus, and a significant decrease in the genera Faecalibacterium, Coprococcus, Prevotella and Roseburia. Comparisons between CD and UC patients revealed a greater abundance of the genera Escherichia, Ruminococcus (R. gnavus), Clostridium, Cetobacterium, Peptostreptococcus in CD patients, and the genera Faecalibacterium, Blautia, Bifidobacterium, Roseburia and Citrobacter in UC patients.ConclusionsMucosa-associated dysbiosis was identified in IBD patients. CD and UC may be distinguishable from the mucosa-associated microbial community structure.

Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice. BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR. Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa. Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

Background: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. Summary: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). Key Message: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.

The relationship between skeletal muscle volume and the prognosis of patients with inflammatory bowel disease (IBD) remains undetermined. We conducted a retrospective study of 72 IBD patients who were admitted to the hospital due to disease exacerbation. We enrolled IBD patients who had undergone abdominal computed tomography and assessed the nutritional indices, such as the Onodera's prognostic nutritional index (O-PNI) and the controlling nutritional status (CONUT) index. The L3 skeletal muscle index (SMI), which is the ratio of the cross-sectional area of skeletal muscles at the level of the third lumbar (L3) vertebra to the height squared, was used to identify sarcopenia. Sarcopenia, defined as a low SMI, was observed in 42% of all IBD patients (37% with Crohn's disease (CD) and 48% with ulcerative colitis (UC)). In UC patients, the O-PNI and CONUT values, height, and albumin levels were significantly lower than in CD patients. The SMI strongly correlated with sex, body weight, albumin level, and O-PNI in IBD patients. Multivariate analysis using the Cox regression model demonstrated that the presence of sarcopenia (P = 0.015) and disease type (CD or UC) (P = 0.007) were significant factors predicting intestinal resection. The cumulative operation-free survival rate was significantly lower for sarcopenic patients than in all IBD patients (P = 0.003) and a stratified analysis of CD patients (P = 0.001) using the Kaplan-Meier method and log-rank test. The L3 skeletal muscle area is a prognostic factor for intestinal resection in patients with CD.

Abstract Background & Hypothesis Psychotic disorders are inequitably distributed by race in the United States, although it is not known whether this is due to assessment biases or inequitable distributions of risk factors. Psychotic experiences are subclinical hallucinations and delusions used to study the etiology of psychosis, which are based on self-report and therefore not subject to potential clinician biases. In this study, we test whether the prevalence of psychotic experiences (PE) varies by race and if this variance is explained by socioenvironmental risk factors. Study Design Data on demographics, PE, and socioenvironmental risk factors were collected through the National Survey of Poly-victimization and Mental Health, a national probability sample of US young adults. Logistic regression analyses were used to determine whether PE prevalence varied by race/ethnicity and, if so, whether this was attenuated with inclusion of indicators of income, education, urban/rural living, discrimination, and trauma exposure. Study Results Black and Hispanic respondents reported PE at significantly greater rates than White or “other” ethnoracial groups, with hallucinations more commonly reported by Hispanic respondents. PE were significantly associated with police violence exposure, discrimination, adverse childhood experiences, and educational attainment. These factors statistically explained ethnoracial differences in the likelihood of overall PE occurrence and of nearly all PE subtypes. Conclusions Previously observed racial differences in psychosis extend beyond clinical schizophrenia, and therefore, are unlikely to be explained entirely by clinician biases. Instead, racial disparities in PE appear to be driven by features of structural racism, trauma, and discrimination.

Interleukin (IL)-36 (IL-36α, IL-36β, and IL-36γ) is a recently reported member of the IL-1 cytokine family. In this study, we investigated IL-36 expression in the inflamed mucosa of patients with inflammatory bowel disease and characterized the proinflammatory actions of IL-36 cytokines in human colonic epithelial cells.MethodsIL-36 mRNA expression was evaluated using real-time PCR. IL-36 protein expression was analyzed using immunoblotting and immunohistochemical technique. Intracellular signaling pathways were evaluated by immunoblotting and by specific siRNA-transfected cells.ResultsThe mRNA expression of IL-36α and IL-36γ, but not of IL-36β, was enhanced in the inflamed mucosa of patients with inflammatory bowel disease, in particular, in ulcerative colitis. Immunohistochemical analysis showed that T cells, monocytes, and plasma cells are the source of IL-36α and IL-36γ in colonic mucosa. DNA microarray analysis indicated that IL-36α induces the mRNA expression of CXC chemokines and acute phase proteins in intestinal epithelial cell line, HT-29 cells. IL-36α and IL-36γ dose-dependently and time-dependently induced the mRNA and protein expression of CXC chemokines (CXCL1, CXCL2, CXCL3 etc.) in HT-29 and Widr cells. Stimulation with IL-36α and IL-36γ assembled MyD88 adaptor proteins (MyD88, TRAF6, IRAK1, and TAK1) into a complex and induced the activation of NF-κB and AP-1 and also the phosphorylation of MAPKs. MAPK inhibitors and siRNAs specific for NF-κB and c-Jun AP-1 significantly reduced IL-36–induced CXC chemokine expression.ConclusionsIL-36α and IL-36γ may play a proinflammatory role in the pathophysiology of inflammatory bowel disease through induction of CXC chemokines and acute phase proteins.

Background The clinical utility of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC) is still controversial. We investigated the efficacy and safety of single FMT for patients with mild to moderately active UC in a Japanese population. Methods Fifty-seven patients were evaluated for eligibility, and 16 patients were excluded. Forty-one patients with UC refractory to standard medical therapy were treated with single FMT by colonoscopic administration. Changes in the fecal microbiota were assessed by 16S ribosomal DNA based terminal restriction fragment length polymorphism analysis. Results At 8 weeks after FMT, no patient achieved clinical remission, and 11 of 41 patients (26.8 %) showed clinical response. The full Mayo score and the Mayo clinical score significantly decreased at week 8 [full Mayo score 5.5 ± 2.4 (mean ± standard deviation) at initiation and 4.6 ± 2.2 at week 8, P  < 0.004; Mayo clinical score 4.0 ± 2.0 at initiation and 3.0 ± 1.9 at week 8, P  < 0.001], but there were no statistically significant effects on the Mayo endoscopic score. No adverse events occurred after FMT or during the follow-up period of 8 weeks. The proportion of Bifidobacterium was significantly higher in the donor feces used for responders than in the donor feces used for nonresponders. The proportion of Lactobacillales and Clostridium cluster IV were significantly higher in the donor feces used for nonresponders. Conclusions Single FMT by colonoscopy was performed safely in all patients, but sufficient clinical efficacy and microbial restoration were not confirmed in patients with mild to moderately active UC.

Background Informal caring is associated with mental health deterioration among young people and impacts their help-seeking ability. Social network can provide social support and mitigate the impact of informal care. However, young carers may avoid identification and withdraw from social networks. Evidence regarding the reciprocal associations between caring, social network, and mental health is scarce. We aimed to investigate the directionality and specificity of the associations among the three factors in young people. Methods This study used three consecutive assessment data (2021–2023; T0–T2) from the Japan COVID-19 and Society Internet Survey. We included 5539 young persons aged ≤ 25 years and 25,445 adults aged 26–59 years. Social network was measured using the Lubben Social Network Scale. Psychological distress was evaluated using the Kessler Psychological Distress Scale. Caring status was retrospectively reported at T2. We employed a random intercept cross-lagged model to detect within-person prospective associations between informal caring, social network, and psychological distress. Results Young persons showed significant directional relationships from increased social network and psychological distress at T0 to increased likelihood of caring at T1 (standardised coefficient: 0.131 and 0.176, respectively; 95% confidence interval, 0.015–0.247 and 0.071–0.282, respectively). Adults aged 26–59 years showed a reverse relationship from caring to increased psychological distress both from T0 to T1 (0.061, 0.009–0.112) and from T1 to T2 (0.042, 0.000–0.084). Conclusions Increased psychological distress and social network preceded the onset of informal caring among young persons. Incorporating psychological distress assessment may benefit the early identification of and support for young carers. The long-term interplay between social networking and informal caring needs further clarification.