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关键词： Cytotoxicity   Gene expression   Inflammation   Mercuric chloride   Oxidative stress   Pyroptosis  

摘要：

关键词： Biologic therapies   Crohn’s disease exclusion diet (CDED)   Exclusive enteral nutrition (EEN)   Non-TNF agents   Partial enteral nutrition (PEN)   Pediatric inflammatory bowel disease   Small molecule inhibitors  

摘要： Purpose of Review: This review summarizes emerging treatment strategies in pediatric IBD. Pediatric physicians should be aware of these newer agents and familiarize themselves with their most common side effects, as they may serve as the first-line providers managing adverse effects of these therapies. Recent Findings: Crohn’s disease (CD) and ulcerative colitis (UC), the two primary subtypes of inflammatory bowel disease (IBD), are commonly managed with immune-modulating therapies. Among the most widely used biologic agents are the tumor necrosis factor inhibitors (TNFis) infliximab and adalimumab. While these agents are effective for many patients, a subset does not respond adequately. Over the past decade, several novel therapies have been approved for adult IBD. Although none of these newer IBD medications are currently approved by the Food and Drug Administration (FDA) for pediatric use, pediatric gastroenterologists are increasingly employing them to treat children with refractory or severe disease. In parallel, specific dietary interventions aimed at reducing inflammation and inducing remission have gained popularity, particularly in pediatric and adult patients with CD. Summary: Emerging biologic and small molecule treatments offer therapeutic solutions to children with IBD in the setting of anti-TNF failure or intolerance. Dietary strategies are also increasingly employed in certain cases of CD in the perioperative period and beyond. An expanding IBD armamentarium means that providers should be aware of indications and important side effect profiles of IBD treatments. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.

关键词： Cytokines   Inflammation   Neuroimmune   Superior cervical ganglia   Sympathetic nervous system   Temporomandibular joint  

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关键词： Chiral metal-organic polyhedron   Gas chromatography   Stationary phase   Separation  

摘要： Chiral metal-organic polyhedra (CMOPs) have come to be recognized as ideal materials for chromatographic enantioseparation owing to their unique molecular recognition ability. Herein, the utilization of a novel chiral stationary phase (CSP) based on CMOP-IL ([Cu12(LIL)12(H2O)12], IL = L-isoleucine) for gas chromatographic separation was explored. A variety of mixtures (n-alkanes, n-alcohols and alkylbenzenes) and multiple isomers were effectively separated on the CMOP-IL capillary column. The separation performance of the CMOP-IL column for most mixtures and isomers is superior to that of the previously reported MOP-V ([Cu12(LV)12(H2O)12], V = L-valine) column. Notably, the CMOP-IL capillary column exhibited excellent enantioselectivity towards various racemates that include alcohols, ethers, aldehydes, epoxides, and amino acid derivatives. In comparison with the commercial beta-DEX 120 column, MOP-V column, and Co-L-GG column, the complementary chiral resolving capabilities of the MOP capillary column were demonstrated in separating racemates. Additionally, the relative standard deviation (RSD) values of retention time and peak area of allyl glycidyl ether and o,m,pnitrotoluene stayed within a range below 1 %, indicating good repeatability and stability of the MOP column in gas chromatographic separation. The study indicates that CMOP based on L-isoleucine, as a novel CSP, holds promising applications in gas chromatography.

关键词： Chronic granulomatous disease (CGD)   CYBB mutation   IFN-γ   Neutrophils   Respiratory burst  

摘要： Background: The CYBB gene encodes the gp91-phox protein, a critical component of the NADPH oxidase complex involved in pathogen clearance. Mutations in CYBB are associated with chronic granulomatous disease (CGD), leading to recurrent bacterial infections. Objective: To understand the genetic causes of Chinese CGD patients. Methods: Exome sequencing was used to identify mutations in CGD patients’ PBMCs, confirmed by Sanger sequencing. Neutrophil respiratory burst capacity was analyzed to correlate with clinical treatment efficacy. Results: We identified five CYBB mutations in six CGD patients from five unrelated Chinese families, including two novel mutations (c.1507A > G:p.T503A, c.1587_1605del:p.529_535del), two rare mutations without functional characterization (c.43A > G:p.I15V, c.125C > A:p.T42K), and one recently reported in a different ethnicity (c.252G > T:p.A84A). Our analysis revealed that these mutations had varying effects on CYBB expression, demonstrating that the synonymous c.252G > T mutation is indeed a splicing mutation, resulting in exon 3 deletion and minimal protein expression. Neutrophils from all patients exhibited defective mitogen-stimulated respiratory bursts. However, only neutrophils with the I15V mutation responded to interferon-γ (IFN-γ) treatment, significantly improving the respiratory capacity defect. Consistent with this, the patient with the I15V mutation showed clinical improvement after two weeks of IFN-γ and anti-bacterial co-treatment. Conclusion: Our findings underscore the diverse effects of CYBB mutations on protein expression and function. More importantly, they suggest that assessing the IFN-γ-mediated potentiation of respiratory burst response in patient’s neutrophils is an effective way to predict the therapeutic efficacy of IFN-γ in treating CGD cases, particularly those with non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis (TB). © The Author(s) 2025.

关键词： Adalimumab   Anastomotic ulcer   Anti-TNF therapy   Crohn’s disease-like lesions   Necrotizing enterocolitis  

摘要： Background: Digestive perianastomotic ulcerations (DPAU) are rare Crohn’s disease (CD)-like lesions that develop following intestinal surgery. Although enteral nutrition and anti-inflammatory agents constitute first-line therapies, 59% of refractory cases require advanced interventions. Emerging evidence implicates tumor necrosis factor (TNF)-α-driven inflammation as a key pathogenic mechanism, yet optimal therapeutic strategies remain undefined. Case summary: A 12-year-old girl with a surgery history of neonatal necrotizing enterocolitis (NEC) presented with severe anemia (hemoglobin: 51 g/L) and chronic abdominal pain. Endoscopy revealed circumferential ulcers at the ileocolonic anastomosis, histologically confirmed as active inflammation without granulomas or evidence of infections. Initial therapy with 3 months enteral nutrition and mesalamine failed. Subcutaneous adalimumab induced endoscopic ulcer healing and hemoglobin normalization (111 g/L) within 3 months. At the 12-month follow-up, sustained clinical remission was observed (hemoglobin: 120 g/L, fecal calprotectin: 45 µg/g), with complete mucosal healing and no adverse events. Conclusions: Early anti-TNF therapy induced rapid and sustained remission in a pediatric patient with DPAU, reinforcing the mechanism that TNF-α-driven inflammation underlies disease pathogenesis. While promising, these findings require validation in larger cohorts. Individualized therapeutic decisions should weigh the risks of recurrence, cost, and long-term biologic safety. © The Author(s) 2025.

摘要： Acute myeloid leukemia (AML) patients present with CD8 exhaustion signatures, and pharmacologic inhibition of checkpoints can have therapeutic benefit. The alarmin IL-33 and its receptor STimulation-2 (ST2) promote activation of tissue-regulatory T cells (T_reg cells) and accelerate malignant progression in solid tumors, but their role in leukemia remains unclear. Here, we show that ST2⁺ T_reg cells are enriched in bone marrow (BM) of humans and mice with AML and promote CD8⁺ T cells depletion and exhaustion. ST2 deficiency in T_reg cells restores CD8⁺ T cell function, decreasing AML growth via retention of ST2⁺ T_reg cells precursors in lymph nodes. AML-activated ST2⁺ T_reg cells lack T-bet, IFN-γ and Bcl-6, and kill intratumoral CD8⁺ T cells by amplified granzyme B-mediated cytotoxicity compared to non-AML primed T_reg cells. Engineered anti-ST2 antibodies induce ST2⁺ T_reg cells apoptosis to extend survival in AML models. Together, our findings suggest that ST2 is a potential checkpoint target for AML immunotherapy. © The Author(s) 2025.

关键词： IL-13Rα1   Th2 immune response   large yellow croaker (Larimichthys crocea)   miR-7565  

摘要：

关键词： Lung squamous cell carcinoma   Tumor microenvironment   Cancer-associated fibroblasts   IL-6   Chemotherapy  

摘要： Chemoresistance remains a major obstacle in the treatment of lung squamous cell carcinoma (LUSC), often leading to suboptimal clinical outcomes. Among the key contributors to this resistance are cancer-associated fibroblasts (CAFs), which are increasingly recognized for their tumor-supportive roles. Despite this, the molecular pathways through which CAFs promote chemoresistance in LUSC are not fully elucidated. This study found that CAFs-derived interleukin-6 (IL-6) upregulated the expression of Specificity Protein 1 (SP1) and the ATPbinding cassette transporter B7 (ABCB7) in LUSC cells exposed to cisplatin and docetaxel. In vitro assays showed a marked decrease in apoptosis in tumor cells co-cultured with CAFs. Consistent with these findings, in vivo xenograft models demonstrated that IL-6-producing CAFs reduced the antitumor efficacy of both chemotherapeutic agents. Elevated serum IL-6 levels also emerged as a potential indicator of poor response to chemotherapy. Our findings suggest that IL-6 secreted by CAFs impairs the cytotoxic effects of cisplatin and docetaxel in LUSC, partly through activation of the PI3K/AKT/NF-kappa B signaling axis. Targeting this IL-6-mediated pathway may offer a promising strategy to overcome chemoresistance and enhance therapeutic outcomes in patients with LUSC.

关键词： (Alphabetical order): Arthritogenic peptide   Axial Spondyloarthritis   HLA-B27   Neutrophils   Neutrophil Extracellular Trap   New Bone Formation   T Cells  

摘要： Purpose of Review Axial spondyloarthritis (axSpA) is a chronic multi-organ rheumatic disease affecting various tissues, and recent key advancements have provided significant insight into understanding its immunopathology. Recent Findings Expanded CD8(+) T cell subsets bearing unique T cell receptor (TCR) motifs (TRAV21/TRBV9) in HLA-B27-positive axSpA patients or those with acute anterior uveitis were recently identified. These T cells can bind to self- and bacterial-derived peptides, supporting the "arthritogenic peptide" hypothesis. Monoclonal antibody-mediated elimination of these expanded T cells has shown potential as a novel treatment for axSpA in a phase II clinical trial, offering a groundbreaking therapeutic approach. In addition to T cells, neutrophils have emerged as important mediators of both inflammation and new bone formation in axSpA, potentially contributing to HLA-B27-independent immune pathomechanisms. Key neutrophil-derived molecules-such as macrophage migration inhibitory factor, hypoxia-inducible factor 1-alpha, caspase recruitment domain-containing protein 9, and neutrophil extracellular traps (NETs)-have been shown in preclinical models to promote Th17-mediated inflammation and reduce regulatory T cell numbers. These mechanisms may be relevant to axSpA pathogenesis and represent potential new therapeutic targets. Summary In recent years, significant progress has been made in understanding the immunopathology of axSpA through both HLA-B27-dependent and -independent mechanisms. However, key questions remain. The pathogenic HLA-B27:05-bound peptides driving CD8(+) T cell expansion remain unidentified. Moreover, due to the diversity of TCR motifs that recognize self- and microbial peptides, therapies targeting a single TCR (e.g., TRBV9) may have limited efficacy. Further research is needed to clarify axSpA pathogenesis across both pathways.