Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.
The aim of the present study was to examine the rate of BRAF mutation and the expression profiles of CK19, galectin-3, CD56, thyroid peroxidase (TPO) and Ki67 in papillary thyroid carcinoma (PTC) and papillary thyroid micro-carcinoma (PTMC). A total of 246 cases of thyroid disease were collected, including PTC, PTMC, nodular goiter (NG) and Hashimoto thyroiditis (HT). The results revealed that CK19 expression was 116/120 in PTC, 61/64 in PTMC, 2/34 in NG and 1/28 in HT. Galectin-3 positive expression was 115/120 in PTC, 60/64 in PTMC, 6/34 in NG and 4/28 in HT. TPO positive expression was 8/120 in PTC, 1/64 in PTMC, 30/34 in NG and 25/28 in HT. CD56-positive expression was 12/120 in PTC, 3/64 in PTMC, 33/34 in NG and 26/28 in HT. Ki67 labeling index was 2.52±0.46% in PTC (120 cases), 2.62±0.52% in PTMC (64 cases), 2.55±0.44% in NG (34 cases) and 2.58±0.48% in HT (28 cases). BRAF mutation rate was 93/120 in PTC, 47/64 in PTMC, 3/34 in NG and 2/28 in HT. These results suggested that expression patterns of CK19, galectin-3, CD56 and TPO and BRAF mutation exhibit diagnosis value in thyroid disease. However, Ki67-positive rate exhibits no notable diagnosis value in thyroid disease.
Granulocyte colony-stimulating factor (G-CSF) is a member of the cytokine family of growth factors that can protect the neurons from focal cerebral ischemia-induced injuries. The intracerebral hemorrhage (ICH) has been widely observed in the clinic; however, the protective effect of G-CSF on ICH is still elusive. We found in the present study that the intraperitoneal injection of G-CSF for 5 days could improve the ICH-induced neuronal behavioral impairment measured by limb placement assay. We also observed that injection of G-CSF could increase the number of stem cells in the specific zone of the hemorrhagic areas, demonstrated by the enhanced expression of nestin. Additionally, G-CSF could also promote the mobilization of circulating hemopoietic stem cells (HSCs) to the damaged brain areas and activate the astrocytes. Our results reveal that G-CSF is also protective for the ICH with the mechanisms involving proliferation of neural stem cells, the migration of HSCs and the activation of astrocytes.
IntroductionWD Repeat Domain Phosphoinositide Interacting 2 (WIPI2) is a WD repeat protein that interacts with phosphatidylinositol and regulates multiprotein complexes by providing a b-propeller platform for synchronous and reversible protein-protein interactions assembled proteins. Ferroptosis is a novel iron-dependent form of cell death. It is usually accompanied with the accumulation of membrane lipid peroxides. Our study is to focus on investigating the effect of WIPI2 on the growth and ferroptosis of colorectal cancer (CRC) cells and its potential mechanism.MethodsWe analyzed the expression of WIPI2 in colorectal cancer versus normal tissues through The Cancer Genome Atlas (TCGA), and the relationship between clinical traits and WIPI2 expression and prognosis was assessed by univariate and multifactorial cox analysis. Next, we constructed the siRNAs targeting the WIPI2 sequence si-WIPI2 to further investigate the mechanism of WIPI2 in CRC cells through vitro experiments.ResultsPublic data from the TCGA platform showed that WIPI2 expression was significantly elevated in colorectal cancer tissues compared to paracancerous tissues, and high WIPI2 expressionpredicted poor prognosis for CRC patients. Moreover, we found that the knockdown of WIPI2 expression could inhibit the growth and proliferation of HCT116 and HT29 cells. Furthermore, we found that the expression level of ACSL4 decreased and that of GPX4 increased when WIPI2 was knocked down, suggesting that WIPI2 can potentially positively regulate CRC ferroptosis. Meanwhile, both NC and si groups were able to further inhibit cell growth activity, as well as increase WIPI2 and decrease GPX4 expression when treated with Erastin, but the rate of cell viability inhibition and the trend of protein changes were more significantly in the NC group than si groups, which indicated that Erastin induced CRC ferroptosis through the WIPI2/GPX4 pathway thereby enhancing the sensitivity of colorectal cancer cells to Erastin.ConclusionsOur study suggested that WIPI2 had a promotional effect on the growth of colorectal cancer cells, and it also played an important role in the ferroptosis pathway.
Hesitant fuzzy preference relations (HFPRs) have been widely applied in multicriteria decision-making (MCDM) for their ability to efficiently express hesitant information. To address the situation where HFPRs are necessary, this paper develops several decision-making models integrating HFPRs with the best worst method (BWM). First, consistency measures from the perspectives of additive/multiplicative consistent hesitant fuzzy best worst preference relations (HFBWPRs) are introduced. Second, several decision-making models are developed in view of the proposed additive/multiplicatively consistent HFBWPRs. The main characteristic of the constructed models is that they consider all the values included in the HFBWPRs and consider the same and different compromise limit constraints. Third, an absolute programming model is developed to obtain the decision-makers’ objective weights utilizing the information of optimal priority weight vectors and provides the calculation of decision-makers’ comprehensive weights. Finally, a framework of the MCDM procedure based on hesitant fuzzy BWM is introduced, and an illustrative example in conjunction with comparative analysis is provided to demonstrate the feasibility and efficiency of the proposed models.
Defects of hesitant fuzzy set (HFS) manifest in actual decision‐making process, so adding probabilities to the values in HFS is necessary. The probabilistic HFS (PHFS) is a useful tool to describe the uncertainty of elements in HFS by introducing occurrence probabilities. However, some important issues in PHFS utilization remain to be addressed. In this study, an outranking method for multicriteria decision making (MCDM) with probabilistic hesitant information is presented. First, the binary relations between two probabilistic hesitant fuzzy elements (PHFEs) are defined on the basis of the elimination and choice translating reality method. Some outranking relations between the alternatives are then introduced. Second, we provide a Hausdorff distance between two PHFEs. The main characteristic of the proposed Hausdorff distance is that it does not require the same length and arrangement of the PHFEs. Third, a maximizing Hausdorff distance deviation method is developed to obtain the evaluation criteria weights under a probabilistic hesitant fuzzy environment. Finally, an illustrative example in conjunction with comparative analysis is used to demonstrate that the proposed method is feasible for practical MCDM problems.
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