Int J Med Sci
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[6]-Gingerol induces Caspase-Dependent Apoptosis in Bladder Cancer cells via MAPK and ROS Signaling.
The anti-cancer effects of [6]-gingerol ([6]-GIN), the main active polyphenol of ginger (Zingiber officinale), were investigated in the human bladder cancer cell line 5637. [6]-GIN inhibited cell proliferation, increased sub‑G1 phase ratios, and depolarized mitochondrial membrane potential. [6]-GIN-induced cell death was associated with the downregulation of B‑cell lymphoma 2 (BCL‑2) and survivin and the upregulation of Bcl‑2‑associated X protein (Bax). [6]-GIN activated caspase‑3 and caspase-9 and regulated the activation of mitogen-activated protein kinases (MAPKs). Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN‑induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment.
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Objective: Evaluate the prognostic value of monocyte-lymphocyte ratio (MLR) in patients with stage I endometrial cancer. Method: Data from 225 patients with stage I endometrioid endometrial cancer who underwent surgical resection between January 2010 and December 2020 were reviewed. The receiver operating characteristic (ROC) curves were generated for the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and MLR. ⋯ In multivariate analysis, grade, depth of myometrial invasion, adjuvant RT, and high MLR were independent prognostic factors for disease-free survival. Conclusion: Elevated MLR was significantly associated poor clinical outcomes in patients with stage I endometrioid endometrial cancer. Our findings suggest that MLR may be clinically reliable and useful as an independent prognostic marker for patients with stage I endometrioid endometrial cancer.
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Purpose: We aimed to determine if lactate dehydrogenase to albumin ratio (LAR) might play a prognostic role for patients with operable colorectal cancer (CRC). Patients and Methods: 1334 operable CRC patients in Wuhan Union Hospital Between July 2013 and September 2017 were enrolled in this study and were randomly appointed them into training (n=954) and validation (n=380) sets. The relationship between LAR and overall survival (OS) and disease-free survival (DFS) were determined by restricted cubic splines (RCS) with Cox regression models. ⋯ LAR was superior to TNM stage for OS as well as DFS and LAR plus TNM stage could add more net benefit than clinical model alone. Moreover, the survival nomograms based on LAR achieved great predictive ability for OS and DFS in operable CRC patients. Conclusions: LAR could be served as a reliable prognostic factor for OS as well as DFS, with more accurate prognostic prediction than current TNM stage for patients with operable CRC.
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Abnormally decreased renal Klotho is linked to endoplasmic reticulum-associated degradation in mice.
Aim: Endoplasmic reticulum-associated degradation (ERAD), which involves degradation of improperly folded proteins retained in the ER, is implicated in various diseases including chronic kidney disease. This study is aimed to determine the role of ERAD in Klotho deficiency of mice and human kidney tubular epithelial cells (HK-2) with renal interstitial fibrosis (RIF). Methods: Following establishment of a mouse RIF model by unilateral ureteral obstruction (UUO), a specific ERAD inhibitor, Eeyarestatin I (EerI), was administered to experimental animals by intraperitoneal injection. ⋯ These observations suggest that UPR was remarkably enhanced in the presence of ERAD inhibition and compensated for excess improperly folded proteins, subsequently contributing to the additional production of mature Klotho protein. Conclusion: ERAD is involved in Klotho deficiency in RIF and its specific inhibition significantly promoted Klotho expression, possibly through enhanced UPR. This may represent a novel regulatory mechanism and new therapeutic target for reversing Klotho deficiency.
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Background: Uterine leiomyoma is the most common benign tumor in women of reproductive age, and it can cause infertility. The growth of uterine leiomyoma is mediated by various steroids and growth factors. The purpose of this study was to evaluate the expression of various growth factors in uterine leiomyoma. ⋯ Post-hoc analysis showed that the TGF-β1 and VEGF inhibitors had a greater inhibitory effect on leiomyoma tissue compared with that of UPA. Conclusion: TGF-β and VEGF inhibitors significantly decreased the viability of uterine leiomyoma cells, showing stronger effects than the conventional drug, UPA. TGF-β1 inhibitors affect both leiomyoma tissue and the normal uterus; thus, targeted local treatment rather than systemic treatment should be considered.