Cancer-associated fibroblasts (CAFs) have been considered as major players in tumor growth and malignancy. In colorectal cancer (CRC), CAFs are attendance in high affluence and little is known about how they impact tumor progression. An increasing number of studies indicated that dysregulation of human urothelial carcinoma associated 1 (UCA1) is associated with progression of tumor and metastasis in various cancers including CRC. Nonetheless, the possible mechanisms of UCA1 actuation in CRC remain poorly understood. To address this, we elucidated the effects of conditioned medium from SW480 CRC cells/Normal fibroblast co-culture (CAF-CM) on UCA1 expression, and the cell proliferation, EMT, invasion and migration of the treated CRC cell were evaluated in vitro. Our study indicated that CAFs dramatically stimulated cell proliferation and migration of CRC cell. Furthermore, CAFs induced the EMT phenotype in CRC cell, with an associated change in the expression of EMT markers including vimentin, E-cadherin, N-cadherin and metastasis-related genes (MMPs). Moreover, we found an increased percentage of CRC cell in the S and G2/M phase induced by CAFs. Our results revealed that CAFs could induce upregulation of UCA1, leading to upregulation of mTOR. Up-regulation of UCA1/mTOR axis suppressed p27 and miR-143 while the expression of Cyclin-D1 and KRAS were significantly increased compared with control. Furthermore, UCA1 silencing in treated CRC cell suggested that upregulation of UCA1, which was induced by CAFs, regulates the expression of downstream key effectors. Taken together, these results highlight the vital role of cooperation between lncRNA UCA1 and mTOR in proliferation and metastasis which support the hypothesis that CAFs may be a prominent therapeutic target of stroma-based therapy in CRC treatment.
Different immunomodulation strategies have been used to manage COVID‐19 due to the complex immune‐inflammatory processes involved in the pathogenesis of this infection. Curcumin with its powerful anti‐inflammatory and antiviral properties could serve as a possible COVID‐19 therapy. In this study, a randomized, double‐blinded, placebo‐controlled trial was performed to investigate the effectiveness and safety of nano‐curcumin oral soft gels as a complementary therapy in moderate–severe COVID‐19 patients. Hydroxychloroquine (HCQ) plus sofosbuvir was routinely administered to all 42 COVID‐19 patients, who were randomly assigned to receive 140 mg of nano‐curcumin or placebo for 14 days. CT scans of the chest were taken, and blood tests were run for all patients at time points of 0, 7, and 14 days. Our results indicated that C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels significantly decreased from baseline in the nano‐curcumin‐treated group on day 7. Furthermore, blood levels of D‐dimer, CRP, serum ferritin, ESR, and inflammatory cytokines including IL‐6, IL‐8, and IL‐10 decreased more significantly in the nano‐curcumin‐treated group after 14 days. Additionally, the nano‐curcumin group showed significant improvements in chest CT scores, oxygen saturation levels, and hospitalization duration. Based on our data, oral administration of nano‐curcumin may be regarded as a promising adjunct treatment for COVID‐19 patients due to its ability to speed up chest clearance and recovery.
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