Cellular and molecular biology (Noisy-le-Grand, France)最新文献

{"title":"Molecular insights into the interaction of Coptis teeta protoberberine alkaloids with human topoisomerase 1B-DNA complex: an integrated computational study.","authors":"Jagadish Babu Dasari, Mahesh Babu Dasari, Aparna Chimalamari, Syed Junied, Bini Chhetri Soren","doi":"10.14715/cmb/2026.72.4.5","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.5","url":null,"abstract":"<p><p>Human topoisomerase 1B (hTopo1B) is a validated anticancer target due to its key role in relieving torsional stress during DNA replication and transcription, as well as its overexpression in rapidly proliferating tumor cells. Camptothecin (CPT) and its derivatives are principal hTopo1B-targeting agents but face challenges including lactone ring instability, dose-limiting toxicities, and acquired drug resistance. This research investigated seven protoberberine alkaloids from Coptis teeta alkaloids-berberine, coptisine, epiberberine, berberastine, jatrorrhizine, palmatine, and fetidine as potential CPT-like hTopo1B inhibitors using comprehensive computational methods. Density functional theory (DFT) calculations showed that six of the seven alkaloids had HOMO-LUMO gaps (2.608-3.015 eV) and electrophilicity indices similar to CPT, suggesting a capacity for charge transfer and DNA intercalation. Molecular docking of the hTopo1B-DNA binary complex (PDB:1A36) revealed that all compounds stabilized the covalent cleavage complex through π-π stacking and hydrogen bonds at the scissile site, with coptisine and epiberberine showing the strongest binding affinities (----10.32 and -10.53 kcal/mol, respectively). Molecular dynamics simulations over 250 ns confirmed the structural stability of the complexes, with low RMSD and RMSF values and minimal fluctuations in the radius of gyration. MM/GBSA and MM/PBSA binding free energy analyses consistently ranked epiberberine as the strongest binder (DG = -18.86 and -14.12 kcal/mol), followed by berberine and coptisine. Per-residue decomposition identified key contacts with the DNA bases DT118, DA17, and DA14, as well as with the protein residues GLU179 and GLY201. All protoberberine analogs showed drug-likeness in ADME profiling, good oral availability, and no PAINS alerts. These findings suggest that protoberberine alkaloids from C.teeta, especially epiberberine, coptisine, and berberine, are promising candidates for next-generation hTopo1B-targeted anticancer therapeutics. Experimental validation is required to confirm the proposed mechanism.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral ribavirin binding to human serum albumin in diabetes and uraemia: A molecular docking study.","authors":"Fahad M Almutairi, Mohammad Rehan Ajmal","doi":"10.14715/cmb/2026.72.4.4","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.4","url":null,"abstract":"<p><p>Human Serum Albumin (HSA) is abundant plasma protein in human blood. It plays a critical role in the transport and distribution of endogenous and exogenous compounds. Protein binding affects free fraction of a drug thus affecting pharmacokinetics and therapeutic efficacy. Glycation of HSA under diabetic conditions and the accumulation of uremic toxins in uraemia may alter drug-protein interactions. Therefore, the present study aimed to investigate the binding interactions of ribavirin and selected uremic toxins with binding interactions involving glycation-sensitive HSA residues using molecular docking analysis. Molecular docking results demonstrated that ribavirin bind to HSA with hydrogen bonding and hydrophobic interactions. Key glycation-prone residues, including ARG222, ARG218, and LYS195, were identified at the ribavirin binding site. Several of these residues were also involved in the binding of uremic toxins, indicating potential competition for ligand binding in diabetic and uremic conditions. The overlap of interaction sites suggests that glycation and toxin accumulation may influence the structural and biochemical properties of HSA, thereby affecting ribavirin binding affinity and distribution. In conclusion, this study highlights the important role of glycation-sensitive HSA residues in mediating ribavirin and uremic toxin interactions. These insights may support the future design and optimization of ribavirin-based therapeutics.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"22-28"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of allergic type 2 immunity in the pathogenesis of Crohn's disease: From epithelial alarmins to IgE signaling.","authors":"Alexander V Blagov, Marina D Sazonova, Anastasia I Ryzhkova, Mikhail A Popov, Alexandra V Mishina, Arkady A Metelkin, Alexander N Orekhov, Igor A Tarakanov, Vasily P Karagodin, Margarita A Sazonova, Yuri V Arkhipenko","doi":"10.14715/cmb/2026.72.4.3","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.3","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by complex interactions between genetic susceptibility, gut microbiota, and immune dysregulation, typically associated with Th1 and Th17 responses. However, emerging evidence highlights that type 2 allergic mechanisms also significantly contribute to CD pathogenesis. This review examines the cellular and molecular basis of allergic pathways in CD, focusing on IgE-mediated hypersensitivity, mast cell and eosinophil effector functions, and Th2 cytokines (IL-4, IL-5, IL-13). Key epithelial-derived alarmins-namely IL-33, TSLP, and IL-25-are discussed as critical upstream mediators linking mucosal barrier injury to type 2 immune activation in the CD gut. Elevated serum IgE, intestinal mast cell infiltration, and tissue eosinophilia have consistently been documented in CD patients. Mechanistically, FcεRI signaling on mast cells triggers degranulation and release of histamine, proteases, and pro-inflammatory cytokines such as TNF-α and IL-6, leading to increased epithelial permeability and visceral hypersensitivity. Moreover, crosstalk between Th2 and Th1/Th17 pathways further amplifies chronic intestinal inflammation. Understanding these allergic mechanisms opens novel therapeutic avenues, including anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-33 (itepekimab), anti-TSLP (tezepelumab), and mast cell stabilizers (ketotifen). This review integrates current molecular evidence on allergic reactions in CD and highlights their clinical and therapeutic relevance. Recognizing type 2 immune signatures in subsets of CD patients may enable more personalized treatment strategies.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"15-21"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chromatin state paradox in alternative lengthening of telomeres.","authors":"Mengjie Xiong, Wenxian Zheng, Tongxin Jia, Kailong Hou, Jiawei Liu, Runzhi Liu, Jing Liu, Kun Wang, Ruoyu Zhou, Shuting Jia","doi":"10.14715/cmb/2026.72.4.7","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.7","url":null,"abstract":"<p><p>Telomeres are protected by the shelterin complex and consist of TTAGGG repeats. Their gradual erosion triggers replicative senescence unless counteracted by telomerase or the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway, utilized by 10-15% of cancers. Accumulating evidence indicates that the decision to activate ALT is intimately linked to the plasticity of telomeric chromatin. This review integrates recent data showing that both constitutive and facultative heterochromatin marks shape ALT activity. We summarize the dynamic regulation of telomeric chromatin and explore the contrasting evidence for two models: the 'open telomeric chromatin model,' where loss of constitutive heterochromatin (e.g., reduced H3K9me3) promotes ALT by increasing chromatin accessibility for homologous recombination (HR) factors, and the 'closed telomeric chromatin model,' where a specific gain of heterochromatic features (e.g., H3K9me3 or H3K27me3) facilitates ALT by creating a specialized phase-separated environment that promotes telomere clustering and break-induced replication (BIR). Resolving this paradox is crucial for understanding ALT initiation and for developing promising synthetic-lethal strategies against ALT-dependent cancers.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"56-66"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium carbonate attenuates behavioral alterations and partially reverses reduced prefrontal BDNF mRNA expression induced by post-weaning social isolation in male rats.","authors":"Hanieh Mansouri Dobarji, Batool Ghorbani Yekta, Mahsa Ale-Ebrahim, Mohadeseh Ghalandari","doi":"10.14715/cmb/2026.72.4.8","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.8","url":null,"abstract":"<p><p>Social isolation is an environmental stressor that can adversely affect behavioral function and neuroplasticity-related pathways. Brain-derived neurotrophic factor (BDNF) is one of the key molecules implicated in these changes. Lithium has been reported to influence neuroplasticity-related signaling and may modulate BDNF expression. In this study, we investigated the effects of lithium carbonate on behavioral alterations induced by chronic post-weaning social isolation in male rats and assessed BDNF mRNA expression in the prefrontal cortex. Rats were subjected to social isolation from postnatal day (PND) 21 to PND 70. Lithium carbonate (20 mg/kg, i.p.) was administered once daily during PND 64-70. Behavioral performance was evaluated using the open field test, hot plate test, marble burying test, and forced swim test. Compared with controls, socially isolated rats showed hyperlocomotion, increased rearing, lower pain threshold, altered immobility behavior in the forced swim test, obsessive-compulsive-like behavior, and reduced prefrontal BDNF mRNA expression. Lithium treatment attenuated several isolation-induced behavioral alterations and was accompanied by a partial reversal of reduced prefrontal BDNF mRNA expression toward control levels. Interpretation of molecular findings should be considered preliminary because gene expression analysis was conducted on a limited number of biological samples (n = 3 per group) and only BDNF mRNA, not BDNF protein, was measured. In conclusion, lithium carbonate improved several behavioral abnormalities associated with chronic social isolation and was associated with changes in prefrontal BDNF mRNA expression in male rats. Further studies are needed to clarify the molecular pathways and causal mechanisms underlying these effects.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"67-76"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH1 gene signaling pathway in the development and progression of carcinomas: an integrative review in cellular and molecular contexts.","authors":"Leticia Milene Silva da Silva, Ana Gabrielly de Melo Matos, Kwang Ii Marciaga Teófilo, João Victor Carvalho, Denner Rodrigo Diniz Duarte, Bruna Larissa Nolêto Sousa, Juliana Martins da Guia Ribeiro do Carmo, Daniel Gomes Monteiro Beltrammi, Joyce Santos Lages, Rita da Graça Carvalhal Frazão, Antonio Augusto Lima Teixeira Júnior, Jaqueline Diniz Pinho, Gyl Eanes Barros Silva","doi":"10.14715/cmb/2026.72.4.1","DOIUrl":"https://doi.org/10.14715/cmb/2026.72.4.1","url":null,"abstract":"<p><p>The NOTCH1 gene and its signaling pathway play a critical role in the oncogenesis and progression of various carcinomas through complex cellular and molecular mechanisms. This integrative literature review examines 21 selected studies across multiple carcinoma types, including head and neck, prostate, penis, breast, and hepatocellular carcinomas, to elucidate the functional impact of notch1 alterations on tumor behavior and clinical outcomes. NOTCH1 functions as a context-dependent regulator, acting either as an oncogene or tumor suppressor according to cellular environment and molecular context. Aberrations in notch1 signaling influence cell proliferation, differentiation, apoptosis, and angiogenesis, thereby contributing to cancer initiation and progression. Despite some variability in findings, the majority of studies indicate that notch1-related molecular changes have significant implications for prognosis and potential therapeutic targeting. This review highlights the importance of understanding notch1 signaling pathways in the cellular and molecular biology of carcinomas, aiming to pave the way for novel diagnostic and treatment strategies.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 4","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific effects of fluoxetine on REM sleep deprivation-induced behavioral impairments and BDNF downregulation in rats.","authors":"Rojin Ehsan, Batool Ghorbani Yekta, Maryam Eslami, Mahdieh Gholami, Salar Vaseghi","doi":"10.14715/cmb/2025.72.3.3","DOIUrl":"https://doi.org/10.14715/cmb/2025.72.3.3","url":null,"abstract":"<p><p>Rapid eye movement (REM) sleep is a critical phase in which most dreaming occurs, and its deprivation (REM SD) can lead to disturbances in mood, cognition, synaptic plasticity, and neuroplasticity-related genes such as brain-derived neurotrophic factor (BDNF). Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is known to modulate BDNF expression, and sex-dependent variations in its effects have been suggested. This study investigated the effects of REM SD, fluoxetine, and their combination on behavioral and molecular outcomes in male and female rats. Results: Following 24 hours of REM SD, animals exhibited impaired memory, increased immobility, reduced rearing, elevated pain threshold, and decreased locomotor activity, along with reduced BDNF levels in the prefrontal cortex. Females were less sensitive to REM SD regarding pain threshold and locomotor activity. Fluoxetine administration (10 mg/kg, i.p.) reversed the effects of REM SD on immobility and rearing exclusively in females, while also mitigating locomotor deficits induced by REM SD. In both sexes, fluoxetine counteracted REM SD-induced changes in pain threshold, but only in females did it restore BDNF downregulation. In conclusion, the findings suggest sex-specific variations in the consequences of REM SD and in the therapeutic response to fluoxetine. While REM SD broadly impairs cognitive, affective, and molecular parameters, females exhibit partial resilience, particularly in pain threshold and locomotor activity. Moreover, fluoxetine demonstrates sex-dependent protective effects, especially in restoring BDNF expression and behavioral outcomes in females.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 3","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR systems in cancer therapeutics and diagnostics.","authors":"Mohsen Almakrami, Zubair Ahmed, Ghadah M Alali, Abdulmajeed Alqurashi","doi":"10.14715/cmb/2025.72.3.2","DOIUrl":"https://doi.org/10.14715/cmb/2025.72.3.2","url":null,"abstract":"<p><p>Cancer is the leading cause of morbidity and mortality globally, underscoring the need for precise diagnostic approaches and effective therapeutic strategies. The invention of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system has transformed cancer research by enabling accurate and efficient genome editing. This review provides a comprehensive overview of CRISPR-based applications in cancer therapeutics and diagnostics, beginning with an introduction to cancer biology and the CRISPR/Cas9 mechanism of action. The therapeutic potential of CRISPR is discussed with a focus on targeting oncogenes, restoring tumor suppressor gene function, and advancing cancer immunotherapy through approaches such as CAR-T cell engineering. The use of CRISPR-based screening platforms to identify genes associated with drug resistance is also examined, along with current challenges including off-target effects, delivery limitations, and ethical considerations, as well as future directions for clinical translation. In addition, the diagnostic capabilities of CRISPR technologies are highlighted, including the detection of circulating tumor DNA, cancer-associated extracellular vesicles, protein biomarkers, and microRNAs. Recent advances in CRISPR/Cas-based strategies aimed at improving detection sensitivity and specificity are summarized. Overall, this review highlights the expanding role of CRISPR systems in cancer diagnosis and therapy and emphasizes their potential to contribute to the development of more personalized and effective cancer management strategies.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 3","pages":"8-18"},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of high-sucrose and high-fat diets on metabolic syndrome, BBB integrity, and hippocampal Aβ accumulation.","authors":"Carlos Francisco Aguilar-Gamas, Eduardo Martínez-Abundis, Erick De la Cruz-Hernández, Nancy P Gómez-Crisóstomo","doi":"10.14715/cmb/2025.72.3.1","DOIUrl":"https://doi.org/10.14715/cmb/2025.72.3.1","url":null,"abstract":"<p><p>Metabolic syndrome (MS) is a global health problem and a recognized risk factor for cognitive impairment and Alzheimer's disease (AD), but the different effects of specific dietary components on MS-related neurological damage remain unclear. This study investigated the effects of long-term high-calorie diets on metabolic parameters, blood-brain barrier (BBB) ​​integrity, and hippocampal β-amyloid (Aβ) accumulation. Male Wistar rats were fed a control diet, a high-sucrose diet (HSD, 30% sucrose in drinking water), or a high-fat diet (HFD, 30% lard) for 12 months. The study assessed metabolic syndrome parameters, spatial memory (Morris water maze), BBB permeability (Evans blue staining), tight junction proteins (ZO-1, Occludin), and the levels of Aβ and its transporters (LRP1, RAGE). The results showed that both HSD and HFD induced central obesity, increased BBB permeability, and spatial memory deficits in rats; however, disruption of the blood-brain barrier was not associated with changes in tight junction protein expression. Notably, hippocampal Aβ accumulation increased only in the high-fat diet group (HFD group) after 8-12 months, associated with a significant downregulation of the Aβ clearance receptor LRP1, while no changes were observed in RAGE. In contrast, the high-fat diet group (HSD group) exhibited more extensive metabolic syndrome-related alterations, including hyperglycemia and hypertension. Our results suggest that while both sucrose- and fat-based high-calorie diets impair the integrity of the blood-brain barrier and cognitive function, only high-fat intake promotes hippocampal Aβ accumulation by downregulating LRP1. These results suggest that although both dietary patterns contribute to metabolic syndrome and cognitive impairment, high-fat intake may pose a more specific risk to Alzheimer's disease pathology.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 3","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKG2D as a molecular link between epithelial stress and immune activation in Crohn's disease: therapeutic implications.","authors":"Alexander V Blagov, Marina D Sazonova, Anastasia I Ryzhkova, Mikhail A Popov, Alexandra V Mishina, Arkady A Metelkin, Alexander N Orekhov, Igor A Tarakanov, Vasily P Karagodin, Margarita A Sazonova, Yuri V Arkhipenko","doi":"10.14715/cmb/2025.72.3.8","DOIUrl":"https://doi.org/10.14715/cmb/2025.72.3.8","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by dysregulated immune responses, epithelial barrier dysfunction, and progressive tissue damage. Despite advances in biologic therapies, treatment resistance and loss of response remain common. The activating receptor NKG2D, expressed on natural killer cells and T cell subsets, recognizes stress-induced ligands (MICA, MICB, ULBP) upregulated on intestinal epithelial cells under inflammatory conditions. In CD, sustained ligand expression promotes NKG2D-dependent cytotoxicity, pro-inflammatory cytokine release (IFN-γ, IL-17), and lymphocyte trafficking into the mucosa, perpetuating a cycle of epithelial injury and chronic inflammation. Preclinical colitis models and clinical trials with anti-NKG2D monoclonal antibodies (e.g., NNC0142-0002) demonstrate reduced disease activity, improved histological outcomes, and induction of remission in moderate-to-severe CD patients. However, challenges remain, including potential impairment of immune surveillance against infections and tumors, patient heterogeneity, and pathway redundancy. Future directions include biomarker-guided patient selection, combination therapies with anti-TNF or anti-integrin agents, and next-generation biologics such as bispecific antibodies. Understanding the cellular and molecular basis of NKG2D signaling in mucosal inflammation positions this receptor as a promising, mechanistically anchored therapeutic target in Crohn's disease.</p>","PeriodicalId":520584,"journal":{"name":"Cellular and molecular biology (Noisy-le-Grand, France)","volume":"72 3","pages":"63-67"},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}