2,3,5,4'-Tetrahydroxystilbene (TG1), a Novel Compound Derived from 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), Inhibits Colorectal Cancer Progression by Inducing Ferroptosis, Apoptosis, and Autophagy.

Article

作者: Chen, Hsin-An ; Chang, Yu-Jia ; Tsai, Kuei-Yen ; Huang, Chien-Yu ; Chang, Yao-Yuan ; Lee, Cheng-Chin ; Liu, Der-Zen ; Makondi, Precious Takondwa ; Wei, Po-Li

BACKGROUNDColorectal cancer (CRC) is one of the deadliest cancers worldwide and long-term survival is not guaranteed in metastatic disease despite current multidisciplinary therapies. A new compound 2,3,5,4'-Tetrahydroxystilbene (TG1), derived from THSG (2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside), has been developed, and its anticancer ability against CRC is verified in this study.METHODSHCT116, HT-29, and DLD-1 were treated with TG1 and the IC₅₀ was measured using a sulforhodamine B assay. A Xenograft mouse model was used to monitor tumor growth. Apoptosis and autophagy, induced by TG1 in CRC cells, were examined. RNA-sequencing analysis of CRC cells treated with TG1 was performed to discover underlying pathways and mechanisms.RESULTSThe results demonstrated that treatment with TG1 inhibited CRC proliferation in vitro and in vivo and induced apoptotic cell death, which was confirmed by Annexin V-FITC/PI staining and Western blotting. Additionally, TG1 treatment increased the level of autophagy in cells. RNA-sequencing and GSEA analyses revealed that TG1 was associated with MYC and the induction of ferroptosis. Furthermore, the ferroptosis inhibitor Bardoxolone abrogated the cytotoxic effect of TG1 in CRC cells, indicating that ferroptosis played a crucial role in TG1-induced cytotoxicity.CONCLUSIONSThese findings suggest that TG1 might be a potential and potent compound for clinical use in the treatment of CRC by inhibiting proliferation and inducing ferroptosis through the MYC pathway.

2021-12-01·The Saudi Dental Journal

Fixation of free gingival grafts with cyanoacrylate glues: A histomorphometric and immunohistochemical study

Article

作者: Silva, Bruno Rocha da ; Silva, Paulo Goberlânio de Barros ; Paula, Dayrine Silveira de ; Alves, Ana Paula Negreiros Nunes ; Cavalcante, Roberta Barroso ; Lima, Lia Vila Real

AIMThe objective of this study was to evaluate the inflammatory process resulting from the use of two cyanoacrylate-based adhesives to stabilize grafts.METHODOLOGYA total of 45 male Wistar rats were randomly divided into three groups (n = 15/group) treated with ethyl cyanoacrylate glue (TG1), octyl-2-cyanoacrylate glue (TG2) or suture threads (CG). After de-epithelialization in the anterior gingival region of the mandible, the graft was removed from the donor site (hard palate), taken to the recipient site and stabilized according to the protocol of each group. After 7, 14, and 45 days, the animals were euthanized. The graft area was analysed macroscopically, histologically, histochemically (Masson trichrome), and immunohistochemically positive cell count for TGF-β, α-SMA, RANKL, OPG, FGF, and IL-10. The Kruskal-Wallis/Dunn test (SPSS 20.0, p < 0.05) was used for analysis.RESULTSThere was no difference in the clinical parameters among the three groups, but TG1 showed the lowest mononuclear inflammatory cell count and the highest amount of total collagen. FGF immunoexpression was significantly higher for the CG group, but the TG2 showed a significant reduction in the RANKL/OPG ratio.CONCLUSIONTG1 had a mild inflammatory response and a higher collagen deposition than other glues, and TG2 had a reduction in the RANKL / OPG ratio.

2020-10-01·Journal of Periodontology2区 · 医学

Omega‐3 PUFA and aspirin as adjuncts to periodontal debridement in patients with periodontitis and type 2 diabetes mellitus: Randomized clinical trial

2区 · 医学

Article

作者: de Marco, Andrea C. ; Andere, Naira M. R. B. ; Santamaria, Mauro P. ; Araujo, Cássia F. ; Van Dyke, Thomas E. ; Castro dos Santos, Nidia C. ; Kantarci, Alpdogan

AbstractBackgroundSupplementation with omega‐3 polyunsaturated fatty acids (ω‐3 PUFA) and low‐dose aspirin (ASA) have been proposed as a host modulation regimen to control chronic inflammatory diseases. The aim of this study was to investigate the clinical and immunological impact of orally administered ω‐3 PUFA and ASA as adjuncts to periodontal debridement for the treatment of periodontitis in patients type 2 diabetes.MethodsSeventy‐five patients (n = 25/group) were randomly assigned to receive placebo and periodontal debridement (CG), ω‐3 PUFA + ASA (3 g of fish oil/d + 100 mg ASA/d for 2 months) after periodontal debridement (test group [TG]1), or ω‐3 PUFA + ASA (3 g of fish oil/d + 100 mg ASA/d for 2 months) before periodontal debridement (TG2). Periodontal parameters and GCF were collected at baseline (t0), 3 months after periodontal debridement and ω‐3 PUFA + ASA or placebo for TG1 and CG (t1), after ω‐3 PUFA + ASA (before periodontal debridement) for TG2 (t1), and 6 months after periodontal debridement (all groups) (t2). GCF was analyzed for cytokine levels by multiplex ELISA.ResultsTen patients (40%) in TG1 and nine patients (36%) in TG2 achieved the clinical endpoint for treatment (less than or equal to four sites with probing depth ≥ 5 mm), as opposed to four (16%) in CG. There was clinical attachment gain in moderate and deep pockets for TG1. IFN‐γ and interleukin (IL)‐8 levels decreased over time for both test groups. IL‐6 levels were lower for TG1. HbA1c levels reduced for TG1.ConclusionAdjunctive ω‐3 and ASA after periodontal debridement provides clinical and immunological benefits to the treatment of periodontitis in patients with type 2 diabetes.

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