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摘要： Cells can sense invading viruses and trigger type I interferons (IFN-α/β) to evoke antiviral innate immune response. Induction of IFNs needs to be fine-tuned to achieve the antiviral consequence while avoiding severe disruption of host cell homeostasis. Here, we reported that NAT10, the acetyltransferase of histone and N4-acetylcytidine (ac4C) RNA modification, promotes infection of RNA viruses via regulation of type I IFN signaling. Depletion of NAT10 increased the expression of IFN-β and interferon-stimulated genes (ISGs) upon stimulation of type I IFN antiviral signaling, while it impaired viral replication. NAT10 dynamically associated with the IFN-β promotor and negatively regulated IRF3 through modulation of long non-coding RNAs (lncRNAs) that inhibit IRFs. Consistently, the small molecule inhibitor of NAT10, Remodelin, increased IFN-β expression while inhibiting viral infections. Overall, our findings indicated that NAT10 is a negative regulator of type I IFN signaling, suggesting its potential as a target of antiviral treatment.

关键词： ASIA   silicone   granuloma   adalimumab   anti-TNF  

关键词： Obstructive sleep apnea   Claudin-4   IL-22   Intestinal repair  

摘要： Background: Obstructive sleep apnea (OSA) is characterized as a low-grade inflammatory condition resulting from injury induced by intermittent hypoxia (IH). Interleukin-22 (IL-22), a mucosa-targeting cytokine, regulates tight junction proteins like Claudin-4 (CLDN4) to enhance barrier function, yet its role in OSA remains underexplored. Methods: This pilot observational study included consecutive patients who underwent polysomnography. Plasma IL-22 and CLDN4 levels were measured using an enzyme-linked immunosorbent assay. Rat models of IH-exposed colon tissues were used for histology and immunohistochemical analysis. All statistical analyses were performed using SPSS 20.0. Results: The expression of plasma IL-22 and CLDN4 was found to be positively correlated in OSA patients (r = 0.512, p < 0.001). Plasma IL-22 and CLDN4 levels exhibited a significant positive correlation with the apnea-hypopnea index (both p < 0.001), arousal index (p = 0.001 and p = 0.014), oxygen desaturation index (p < 0.001 and p = 0.001), and T90 (r = 0.379, p < 0.001 and p = 0.002). They also exhibited significant negative correlations with sleep efficiency (0.029;p = 0.004), REM sleep phases (p = 0.037 and p = 0.015), and mean oxygen saturation (SpO(2)) (p = 0.044 and p = 0.006). Plasma IL-22 and CLDN4 were significantly increased in the OSA group (p < 0.001), especially in severe OSA. The diagnostic value of plasma IL-22 combined with CLDN4 was superior to that of other indicators, with an AUC of 0.849 (0.783-0.915) for diagnosing OSA and an AUC of 0.909 (0.856-0.961) for diagnosing severe OSA. Pathological staining of the rat colon confirmed the damage of intermittent hypoxia (IH) to the intestine. The rat IH group had more IL-22 in the intestinal lymph node and more CLDN4 in the intestinal epithelium than the normal control (NC) group. The expression trends of IL-22 and CLDN4 in rat plasma were consistent with those observed in tissue samples. Conclusion: Plasma IL-22 and CLDN4 were assoc

关键词： Donor lymphocyte infusion   HLA-haploidentical hematopoietic   transplantation   Adult T -cell leukemia/lymphoma  

摘要： Donor lymphocyte infusion (DLI) combined with chemotherapy is an effective therapy for relapsed adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-matched related donor or matched unrelated donor. The 1-year incidence of ATL relapse is 28 % after HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide. However, the efficacy of DLI for relapsed ATL after haplo-HSCT remains unclear. Here, we present the case of a 61-year-old woman diagnosed with ATL who underwent haplo-HSCT from an HLA-haploidentical relative donor. On day +164 after transplantation, the patient experienced ATL relapse. Tacrolimus was tapered and discontinued on day +216;however, ATL progressed. Since the patient did not develop graft-versus-host disease (GVHD) after the discontinuation of tacrolimus, DLI following chemotherapy was performed for relapsed ATL. The patient achieved complete remission without severe GVHD after the 6th DLI treatment. This remission has been sustained for over 15 months with 13 DLI treatments. These results suggest the potential of DLI combined with chemotherapy as a treatment option for patients with relapsed ATL after haplo-HSCT.

关键词： ESR1   Hotspot mutations   Neoepitopes   HLA-A2   Immunotherapy  

摘要： Endocrine therapy has shown significant clinical efficacy in estrogen receptor alpha (ER alpha)-positive breast cancer management, but the emergence of therapy-resistant mutations significantly undermines treatment outcomes, frequently leading to disease progression and metastasis. Among these resistance mechanisms, mutations in the ESR1 gene are particularly prevalent, detectable in 76% of endocrine therapy-resistant tumor specimens. The identification of immunogenic neoepitopes derived from mutant ESR1 offers a promising therapeutic avenue for patients with endocrine therapy-resistant breast cancer. In this study, we systematically investigated the mutational landscape of ESR1 across various cancer types, with particular emphasis on mutation frequency and spectrum analysis. Our findings revealed that non-synonymous ESR1 mutations predominantly occurred in breast cancer, clustering at four distinct hotspot sites: K303, E380, Y537 and D538. We further characterized the mutation prevalence at these hotspots across different breast cancer subtypes. Through comprehensive screening, we identified eight human leukocyte antigen (HLA)-A*0201 restricted immunogenic neoepitopes derived from ESR1 hotspot mutations. These neoepitopes demonstrated the capacity to elicit specific cytotoxic T lymphocytes (CTLs) responses both in vitro and in vivo. The induced CTLs exhibited specific recognition and cytotoxic activity against both T2A2 cells loaded with mutant neoepitopes and HLA-A*0201-positive breast cancer cells transfected with minigene encoding mutant neoepitopes. Notably, adoptive transfer of T cells primed with a peptide pool containing these eight neoepitopes significantly suppressed tumor growth and enhanced CD8+ T cells infiltration within tumor tissue. These findings suggest that the identified neoepitopes represent promising candidates for the development of tumor shared neoantigen vaccines.

关键词： gastric cancer   growth   interleukin-21 receptor   long non-coding RNA MALAT1   miR-125a-3p  

摘要： Following the publication of the above article, an interested reader drew to the authors' attention that their paper was found to contain data with a previous article that had been published in the journal (Figs. 2C and 4B), and in a paper that appeared subsequently in the journal Molecular Cancer. All cases involved the sharing of Transwell assay data, and the other papers in question were published by the same authors/the same research group. After having examined their original data, the authors realized that Figs. 2 and 4 had been inadvertently assembled incorrectly in the above paper. Specifically, Figs. 2C and D, and 4B and D, showing the results of Transwell assay experiments indicating the effects of IL‑21R knockdown or co‑transfection with IL‑21R and miR‑125a mimic on cell invasion in HGC‑27 and MKN‑45 cell lines, contained erroneous images. The revised versions of Figs. 2 and 4, featuring replacement data for Figs. 2C and D and 4B and D, showing the correct data obtained for the effects of IL‑21R knockdown or co‑transfection with IL‑21R and miR‑125a mimic on cell invasion, are shown on the next page. All authors confirm that the errors made in Figs. 2C and D and 4B and D did not influence the final conclusions reported in the above article, and they thank the Editor of for granting them the opportunity to publish a Corrigendum. All the authors agree to the publication of this Corrigendum, and apologize for the inconvenience to the readers. [International Journal of Oncology 54: 7‑16, 2019; DOI: 10.3892/ijo.2018.4612].

关键词： span>APPantigen processing and presentationbpbase pairCDScoding sequencesDRiPsDefective ribosomal productsFDRfalse discovery rateHLA-1Human Leucocyte Antigen class IMSmass spectrometryMWmolecular weightsORFsopen reading framesPCPSproteasome-catalyzed peptide splicingRTretention timesSPIsnakeSpliced Peptide Identification, Search space Navigation And K-mer filtering Engine  

关键词： Galectin‐3   Smad3   idiopathic pulmonary fibrosis   metformin   stearic acid  

摘要： Pulmonary fibrosis (PF) is a chronic, inflammatory interstitial lung disease. It is promoted by overproliferation of fibroblasts characterized by the progressive formation of scar tissue in the lung parenchyma, which leads to an inexorable decline in lung function, respiratory failure, and high mortality. This study aims to assess the synergetic consequences of metformin and stearic acid, whether individually or in combination, to ameliorate bleomycin-induced PF in rat models via suppressing Gal-3/Smad3/α-SMA and TNF-α/NF-κβ signaling pathways and mitigate its adverse side effect on kidneys and liver. The antioxidant/oxidative stress shuttle system was estimated in lung, liver, and kidney tissues. Moreover, histopathology assessment and immunohistochemical staining for NF-κβ antibodies were performed in the lung and trachea tissues. Additionally, RT-qPCR gene expressions of TNF-α, IL-1β, IL-6, and α-SMA were investigated. The expression levels of Gal-3, p-Gal-3, Smad3, and p-Smad3 protein in lung tissues were determined by western blot analysis. The findings showed that metformin and/or stearic acid exhibited antifibrotic and anti-inflammatory impacts in-vivo as evidenced by enhanced body weight, liver and kidney functions, reduced oxidative stress, increased endogenous antioxidant enzymes, downregulated inflammatory cytokine levels IL-1β, IL-6, and TNF-α, and attenuation effect on α-SMA, a major marker of myofibroblasts. Furthermore, there was a marked improvement in the profibrotic Gal-3/Smad3 signaling pathway. On the other hand, a significant reduction in the histological score of fibrosis and immunohistochemical expression NF-κβ levels was detected, especially in the combination-treated group. Overall, our findings elucidate the synergetic antifibrotic impact of metformin and stearic acid which could be used as a potential candidate drug against various chronic inflammatory diseases.