Wolfeaxelsen5297

In rats, intraportal vein injection of NPY activates pSREBP2, mSREBP2, and HMGCR protein expression, and induces hepatic cholesterol accumulation. In BRL-3A cells, we observed that NPY increases cholesterogenic protein expression and cholesterol synthesis through Y1 and Y5 receptors. This effect is mediated by the activation of the ERK1/2 signaling pathway.

We demonstrated, for the first time, that NPY can activate the cholesterogenic pathway and elucidated the underlying mechanism. Thus, NPY and NPY receptors might be new targets for the treatment of NAFLD and dyslipidemia.

We demonstrated, for the first time, that NPY can activate the cholesterogenic pathway and elucidated the underlying mechanism. Thus, NPY and NPY receptors might be new targets for the treatment of NAFLD and dyslipidemia.

Cervical cancer (CC) is a common tumor of women worldwide. Here, we conducted a non-targeted lipidomic study to discover novel lipid biomarkers for early-stage CC.

The lipidomic analysis of 71 samples in discovery set and 72 samples in validation set were performed by coupling ultra-high-pressure liquid chromatography (UHPLC) with quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS). Lipids with variable importance (VIP) values greater than 1, adj. p<0.05 (the adjusted p value obtained from false discovery rate correction) and fold change (FC) higher than 1.5 were reserved as potential biomarkers. Subsequently, receiver operating characteristic (ROC) curve and binary logistic regression were implemented to assess the diagnostic potential of these biomarkers and to acquire the best biomarker combination.

A lipid biomarker panel, including phosphatidylcholine (PC, PC 140/182) and phosphatidylethanolamine (PE, PE 151e/226 and PE 161e/182), was established. This panel was effective in distinguishing between CC and non-CC (squamous intraepithelial lesions [SIL] and healthy controls) within the area under the ROC curve (AUC), sensitivity, and specificity reaching 0.966, 0.952, and 0.860 for discovery set and 0.961, 0.920, and 0.915 for external validation set. Furthermore, this panel was also capable of discriminating early-stage CC from SIL with AUC, sensitivity, and specificity reaching 0.946, 0.952, and 0.800 for discovery set and 0.956, 0.960, and 0.815 for external validation set.

The combination of PC 140/182, PE 151e/226, and PE 161e/182 could serve as a promising serum biomarker for discriminating early-stage CC from SIL and healthy subjects.

The combination of PC 140/182, PE 151e/226, and PE 161e/182 could serve as a promising serum biomarker for discriminating early-stage CC from SIL and healthy subjects.

Glioblastoma (GBM) is the most common subtype of brain cancer, encompassing 16% of all primary brain cancers. The prognosis of GBM is poor, with a 5-year-survial of approximately 5%. Increasing evidence has revealed that chemokines in the tumor microenvironment (TME) are often altered, thus affecting tumor proliferation and metastasis.

Multi-omics and bioinformatics tools were utilized to clarify the role of CXC chemokine in GBM.

Most CXC chemokines were found to be differentially regulated in GBM, which correlated with patient prognosis. CXC chemokines were found to activate cancer-related signaling pathways, thus affecting immune infiltration. Interestingly, this was found to be associated with drug resistance. Most CXC chemokines were significantly correlated with abundance of B cells, CD8+ cells and dendritic cells. Furthermore, somatic copy number alterations of CXC chemokines can inhibit dendritic cell infiltration. Moreover, CXCL1 was selected as a hub gene, and several kinase, miRNA and transcription factor targets of CXCL1 were identified.

our study provides novel insights into CXC chemokine expression and their role in the GBM microenvironment. These results are able to provide more data about prognostic biomarkers and therapeutic targets of GBM.

our study provides novel insights into CXC chemokine expression and their role in the GBM microenvironment. These results are able to provide more data about prognostic biomarkers and therapeutic targets of GBM.Autosomal recessive congenital ichthyosis (ARCI) is a diverse group of cornification diseases associated with severe clinical complications and decreased quality of life. Germline mutations in the TGM1 gene, which encodes the enzyme TGM1, are the predominant cause of ARCI. These TGM1 mutations trigger the abnormal epidermal differentiation and impaired cutaneous barrier function observed in patients with ARCI. Unfortunately, current ARCI therapies focus solely on symptomatic relief. Thus, there is a significant unmet need for therapeutic strategies aimed at correcting the TGM1 deficiency underlying ARCI. In this study, we investigated the ability of KB105, a gene therapy vector encoding full-length human TGM1, to deliver functional human TGM1 to keratinocytes. In vitro, KB105 efficiently infected TGM1-deficient human keratinocytes, produced TGM1 protein, and rescued transglutaminase enzyme function. In vivo studies demonstrated that both single and repeated topical KB105 administration induced TGM1 protein expression in the target epidermal layer without triggering fibrosis, necrosis, or acute inflammation. Toxicity and biodistribution assessments on repeat dosing indicated that KB105 was well-tolerated and restricted to the dose site. Overall, our results demonstrate that rescuing TGM1 deficiency in patients with ARCI through topical KB105 application represents a promising strategy for safely and noninvasively treating this debilitating disease.

Carbon ion radiation therapy (CIRT) is recognized as an effective alternative treatment modality for early stage lung cancer, but a quantitative understanding of relative biological effectiveness (RBE) compared to photon therapy is lacking. In this work, a mechanistic tumor response model previously validated for lung photon radiotherapy was used to estimate the RBE of CIRT compared to photon radiotherapy, as a function of dose and the fractionation schedule.

Clinical outcome data of 9 patient cohorts (394 patients) treated with CIRT for early stage lung cancer, representing all published data, were included. Perhexiline Fractional dose, number of fractions, treatment schedule, and local control rates were used for model simulations relative to standard photon outcomes. Four parameters were fitted α, α/β, and the oxygen enhancement ratios of cells either accessing only glucose, not oxygen (OER

), or cells dying from starvation (OER

). The resulting dose-response relationship of CIRT was compared with the previously determined dose-response relationship of photon radiotherapy for lung cancer, and an RBE of CIRT was derived.