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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Wang, ZC, et al.
(författare)
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A diagnostic model for predicting type 2 nasal polyps using biomarkers in nasal secretion
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1054201-
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Tidskriftsartikel (refereegranskat)abstract
- Predicting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) may help for selection of appropriate surgical procedures or pharmacotherapies in advance. However, an accurate non-invasive method for diagnosis of type 2 CRSwNP is presently unavailable.MethodsTo optimize the technique for collecting nasal secretion (NasSec), 89 CRSwNP patients were tested using nasal packs made with four types of materials. Further, Th2low and Th2highCRSwNP defined by clustering analysis in another 142 CRSwNP patients using tissue biomarkers, in the meanwhile, inflammatory biomarkers were detected in NasSec of the same patients collected by the selected nasal pack. A diagnostic model was established by machine learning algorithms to predict Th2highCRSwNP using NasSecs biomarkers.ResultsConsidering the area under receiver operating characteristic curve (AUC) for IL-5 in NasSec, nasal pack in polyvinyl alcohol (PVA) was superior to other materials for NasSec collection. When Th2low and Th2highCRSwNP clusters were defined, logistic regression and decision tree model for prediction of Th2highCRSwNP demonstrated high AUCs values of 0.92 and 0.90 respectively using biomarkers of NasSecs. Consequently, the pre-pruned decision tree model; based on the levels of IL-5 in NasSec (≤ 15.04 pg/mL), blood eosinophil count (≤ 0.475*109/L) and absence of comorbid asthma; was chosen to define Th2lowCRSwNP from Th2highCRSwNP for routine clinical use.ConclusionsTaken together, a decision tree model based on a combination of NasSec biomarkers and clinical features can accurately define type 2 CRSwNP patients and therefore may be of benefit to patients in receiving appropriate therapies in daily clinical practice.
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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Dai, QQ, et al.
(författare)
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Genetic advances in Meniere Disease
- 2023
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Ingår i: Molecular biology reports. - : Springer Science and Business Media LLC. - 1573-4978 .- 0301-4851. ; 50:3, s. 2901-2908
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Tidskriftsartikel (refereegranskat)abstract
- Meniere Disease (MD) is an idiopathic inner ear disease with complex etiology and pathogenesis, which is still unclear. With the development in gene analysis technology, the genetic research of MD has attracted extensive attention, resulting in a large number of studies on the research of the relationship between human genes and MD. This paper aims to review the studies on this topic in recent years. The studies mainly focused on the genetics of familial MD and the correlation between MD and potentially related functional genes. The results of these studies have demonstrated the complexity and diversity of the pathogenesis of MD with both genetic and epigenetic alterations, suggesting that MD might be related to inflammation, immunity, aqua and ion balance in the lymphatic fluid, virus infection, metabolism, and abnormal function of nerve conduction. The finding of rare mutations in TECTA, MYO7A and OTOG genes and other genes such as CDH23, PCDH15 and ADGRV1 in the same families suggest that the integrity of the stereocilia and their interaction with the tectorial and otolithic membranes could be involved in the pathophysiology of familial MD.
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- Du, QQ, et al.
(författare)
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FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis
- 2022
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:5, s. 488-
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
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- Sun, XT, et al.
(författare)
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Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism
- 2022
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 71:1, s. 129-147
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.DesignTwo unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33–ST2–CXCL3–CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.ResultsIL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33–ST2–MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3–CXCR2 signalling. Type III collagen was identified as the CXCL3–CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.ConclusionsOur work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
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| 25. |
- Tong, BS, et al.
(författare)
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Efficacy of Various Corticosteroid Treatment Modalities for the Initial Treatment of Idiopathic Sudden Hearing Loss: A Prospective Randomized Controlled Trial
- 2021
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Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1421-9700. ; 26:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Objective:</i></b> To evaluate the efficacy of systemic and intratympanic steroid treatment in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). <b><i>Methods:</i></b> Ninety patients who met the inclusion criteria were randomly divided into 3 groups (<i>n</i> = 30 per group). Group I patients were given oral methylprednisolone (MEPD) tablets, group II received intravenous MEPD injection, and group III received intratympanic MEPD injection. Pure-tone average (PTA) hearing threshold was recorded before and after treatment as well as 1 month later. The general efficacy rate was the ratio of patients whose hearing improved by >10 dB in each group. <b><i>Results:</i></b> Thirty-two of the 60 patients (53.3%) in groups I and II together showed a hearing improvement of >10 dB hearing level (HL) in the pure-tone audiogram, compared to 21 patients (70%) in group III, respectively. The mean improvements were 16.1, 14.3, and 21.6 dB HL measured in Groups I, II, and III, respectively. Both the general efficacy rate and hearing improvement were significantly greater in group III than in groups I and II. <b><i>Conclusions:</i></b> Our study showed that intratympanic injection rendered better treatment efficacy than systemic administration.
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