Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-β1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-β1-induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT-related proteins in SGC-7901 cells incubated with or without TGF-β1. The expression of TRPC1/3/6 and EMT-related molecules, including E-cadherin, vimentin, and α-SMA, was detected by qRT-PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following TGF-β1 stimulation, the expression of vimentin, α-SMA, and TRPC1/3/6 increased and E-cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF-β1-induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.
Arginine-rich dipeptide repeat proteins (R-DPRs), abnormal translational products of a GGGGCC hexanucleotide repeat expansion in
C9ORF72
, play a critical role in
C9ORF72
-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the most common genetic form of the disorders (c9ALS/FTD). R-DPRs form liquid condensates in vitro, induce stress granule formation in cultured cells, aggregate, and sometimes coaggregate with TDP-43 in postmortem tissue from patients with c9ALS/FTD. However, how these processes are regulated is unclear. Here, we show that loss of poly(ADP-ribose) (PAR) suppresses neurodegeneration in c9ALS/FTD fly models and neurons differentiated from patient-derived induced pluripotent stem cells. Mechanistically, PAR induces R-DPR condensation and promotes R-DPR–induced stress granule formation and TDP-43 aggregation. Moreover, PAR associates with insoluble R-DPR and TDP-43 in postmortem tissue from patients. These findings identified PAR as a promoter of R-DPR toxicity and thus a potential target for treating c9ALS/FTD.
In this study, galactomannan (GM), including guar gum (GG) or locust bean gum (LG), was incorporated into a κ-carrageenan film to improve barrier properties and reduce the swelling ratio (SR). The effects of that with different concentrations on optical, mechanical, barrier, swelling and thermal properties of the κ-carrageenan-based film were researched. SEM and rheological results showed that both κ-carrageenan/GG and κ-carrageenan/LG had good compatibility and stability. FTIR results showed that LG was easier to form hydrogen bonds with κ-carrageenan. The KC-L exhibited excellent mechanical properties, barrier properties, and SR than KC-G. The film with 15% GM had good light transmittance. Moreover, the thermal stability of the film could be improved by adding GMs. This study reports that the κ-carrageenan–GM film has potential in packaging applications.
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