Urolithin A (UroA) is a first-in-class natural compound derived from gut microbiota metabolites of ellagitannins. This research firstly evaluates the mechanisms of UroA inhibiting advanced glycation end-products (AGEs) formation by...

The protein homeostasis (proteostasis) network (PN) encompasses mechanisms that maintain proteome integrity by controlling various biological functions. Loss of proteostasis leads to toxic protein aggregation (proteotoxicity), which underlies the manifestation of neurodegeneration. How the PN responds to dissimilar proteotoxic challenges and how these responses are regulated at the organismal level are largely unknown. Here, we report that, while torsin chaperones protect from the toxicity of neurodegeneration-causing polyglutamine stretches, they exacerbate the toxicity of the Alzheimer's disease-causing Ab peptide in neurons and muscles. These opposing effects are accompanied by differential modulations of gene expression, including that of three neuropeptides that are involved in tailoring the organismal response to dissimilar proteotoxic insults. This mechanism is regulated by insulin/IGF signaling and the transcription factor SKN-1/ NRF. Our work delineates a mechanism by which the PN orchestrates differential responses to dissimilar proteotoxic challenges and points at potential targets for therapeutic interventions.

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Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. SPRY4 has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of SPRY4 were measured in CRC cell lines. SPRY4 -overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the in vivo tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of SPRY4 in CRC cell lines compared with normal cell line, and the overexpression of SPRY4 significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon SPRY4 silencing was reversed by EZH2 inhibition. In addition, we found that the overexpression of SPRY4 inhibited tumorigenesis in vivo by diminishing the size and weight of the tumors. Our study indicates that SPRY4 might be a potential tumor suppressor gene and prognostic factor for patients with CRC.

Introduction Non–small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and effective treatment for this disease is still lacking. This study aimed to explore the potential role of LINC00518 and miR216b-5p on cell proliferation and tumor growth in NSCLC. Methods The expression of LINC00518, miR216b-5p, MMP7, and MMP9 in NSCLC cell lines was determined by RT-qPCR analysis, which was also used to confirm the transfection effects. After transfection, proliferation, clone-formation ability, migration, and invasion of NSCLC cells were detected by CCK8, clone-formation, wound-healing, and transwell assays, respectively. Western blot analysis was used to detect the expression of MMP7, MMP9, Ki67, and PCNA. A xenograft model was constructed by subcutaneous injection of transfected NSCLC cells into nude mice. Results The results indicated that LINC00518 expression was increased and miR216b-5p expression decreased in NSCLC cell lines, and A549 cells were chosen for the next experiments. LINC00518 interference inhibited proliferation, invasion, and migration of A549 cells, together with the progression of NSCLC in vivo. In addition, LINC00518 directly targeted miR216b-5p. Downregulation of miR216b-5p weakened the inhibitory effect of LINC00518 interference on proliferation, invasion, and migration of A549 cells, as well as progression of NSCLC in vivo. Discussion In conclusion, LINC00518 interference inhibits NSCLC, which is partially reversed by downregulation of miR216b-5p expression.