Peelekrogh3774

The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes might serve as non-invasive biomarkers for SONFH.Circular RNAs (circRNAs) have been demonstrated to play critical roles in the initiation and development of breast cancer (BC). This study aimed to uncover the regulatory roles of a novel circRNA, circRPPH1 (hsa_circ_0000514) in BC progression. CircRPPH1, miR-296-5p and FOXP4 levels were determined by qRT-PCR. CircRPPH1 stability was detected in response to ribonuclease (RNase) R digestion and actinomycin D treatment. Cell growth, migration and invasion were evaluated using various functional experiments. Protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), hexokinase 2 (HK2) and forkhead box protein 4 (FOXP4) were measured by Western blotting. Metabolic alterations of BC cells were evaluated using commercial kits. The interaction between miR-296-5p and circRPPH1/FOXP4 was assessed using dual-luciferase assay, RNA pull-down, and RNA immunoprecipitation (RIP) assay. The in vivo tumorigenesis was assessed in nude mice. According to the results, up-regulation of circRPPH1 was closely correlated with the poor prognosis of BC patients. Functional experiments showed that knockdown of circRPPH1 repressed BC cell growth, migration, invasion, glycolysis, and in vivo tumor growth. In addition, circRPPH1 could sponge miR-296-5p to enhance FOXP4 expression in BC cells. miR-296-5p inhibition or FOXP4 overexpression restored the malignant properties of circRPPH1-silenced BC cells. Thus, circRPPH1 promoted BC malignant progression through regulating miR-296-5p/FOXP4 axis, indicating a possible novel therapeutic strategy involving circRNA for BC patients.Sepsis-associated encephalopathy (SAE) is a serious and diffuse cerebral dysregulation with a high morbidity and mortality caused by sepsis. Mitophagy plays an important role in SAE, and microglial phagocytosis of apoptotic cells (efferocytosis) is the core of the brain regenerative response. Voltage dependent anion channel (VDAC1) is an important regulator of mitophagy. However, it remains unknown whether VDAC1 influences SAE progression by regulating mitophagy and efferocytosis. Herein, we explored the mechanism where knockdown of VDAC1 alleviated the cognitive dysfunction caused by sepsis-associated encephalopathy and further elucidated the underlying molecular mechanisms. SAE model in mice was established through caecal ligation and puncture (CLP). The increased mitophagy and decreased efferocytosis were observed by the transmission electron microscope (TEM) in the SAE model. Besides, immunoblot tests showed an interaction between autophagy and efferocytosis. Further behavior tests and TEM results indicated that knockdown of VDAC1 alleviated the cognitive dysfunction by decreasing the autophagy and increasing the efferocytosis in a PINK1/Parkin-dependent manner. Based on these results, we conclude that knockdown of VDAC1 alleviates the cognitive dysfunction in the CLP-induced SAE mouse model.

Long non-coding RNA (lncRNA) has gradually received widespread attention due to its role in regulating tumor progression. However, in renal cell cancer (RCC), the exact function of lncRNA LINC00671 remains uncertain.

Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for detecting LINC00671 and miR-221-5p expressions in RCC tissues and cell lines. Western blotting technique was utilized for detecting the expressions of epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin and N-cadherin) and suppressor of cytokine signaling 1 (SOCS1). The correlation between clinicopathological features and LINC00671 expression was also evaluated. RCC cell multiplication, migration and invasion were measured by CCK-8, EdU and Transwell assays, respectively. The targeted relationships between LINC00671 as well as the SOCS1 3'UTR and miR-221-5p were verified by RNA immunoprecipitation (RIP) and luciferase reporter gene assay.

LINC00671 expression in RCC tissues and cells was significantly reduced. selleck Patients with low LINC00671 expression had relatively shorter disease-free survival and overall survival. Moreover, LINC00671 expression was linked to lymph node metastasis, tumor stage, and tumor size. In Caki-1 and 769-P cell lines, LINC00671 overexpression restrained the multiplication, migration, invasion, as well as the EMT process of RCC cells

. In terms of mechanism, miR-221-5p was identified as a target of LINC00671, and LINC00671 could up-regulate SOCS1 by repressing miR-221-5p.

LINC00671 regulates the miR-221-5p/SOCS1 axis as a tumor suppressor in RCC.

LINC00671 regulates the miR-221-5p/SOCS1 axis as a tumor suppressor in RCC.Sorafenib is a first-line drug to treat advanced hepatocellular carcinoma (HCC), which can prolong the median overall survival of patients by approximately 3 months. Phenformin is a biguanide derivative that has been shown to exhibit antitumor activity superior to that of metformin. We herein explored the ability of phenformin to enhance the anti-cancer activity of sorafenib against HCC and the mechanisms underlying such synergy. The Hep-G2 and SMMC-7721 HCC cell lines were treated with sorafenib and/or phenformin, after which the proliferation of these cells was evaluated via MTT and colony formation assays, while invasion and apoptotic cell death were evaluated via Transwell and flow cytometry assays, respectively. In addition, protein levels were assessed by Western blotting, drug synergy was assessed with the CompuSyn software, and xenograft models were established by implanting Hep-G2 cells into nude mice and then assessing drug antitumor efficacy. Sorafenib and phenformin exhibited a synergistic ability to suppress HCC cell proliferation, migration, and survival. Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Strikingly, the combination of these two drugs achieved better in vivo efficacy in a murine model system, without causing significant weight loss or hepatorenal toxicity. Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer.

TCM treatment for lung carcinoma has been reported by many researches. Shiquan Yuzhen Decoction can be used in the clinical treatment of lung carcinoma, but its specific mechanism is still under exploration at present.

The active ingredients and mechanism of Shiquan Yuzhen Decoction on non-small cell lung carcinoma were discussed by network pharmacology. The main active ingredients, targets and disease genes of non-small cell lung carcinoma of Shiquan Yuzhen Decoction were screened through relevant databases. Lewis lung carcinoma bearing mice model was established by inoculating Lewis lung carcinoma cells to C57BL/6 mice under the right armpit. Different doses of Shiquan Yuzhen Decoction were used to observe the apoptosis and angiogenesis changes of tumor tissues in mice.

A total of 26 key active compounds meeting the evaluation of generic properties and 182 main targets were screened out. The multi-level network model shows that Shiquan Yuzhen Decoction can regulate the target gene network of non-small cell lung carcinoma. And it can inhibit tumor growth in tumor-bearing mice, induce apoptosis of tumor cells, and evidently increase the activities of Caspase-3, 8 and 9. The dose of 17.4 g/kg can evidently inhibit the formation of microvessels in transplanted tumor tissues, improve the sensitivity of mice's diet and activities, increase the spleen index of tumor-bearing mice, and inhibit inflammatory factors.

Shiquan Yuzhen Decoction can evidently improve the quality of life of Lewis lung carcinoma-bearing mice and inhibit tumor growth in mice, which is a potential clinical treatment plan.

Shiquan Yuzhen Decoction can evidently improve the quality of life of Lewis lung carcinoma-bearing mice and inhibit tumor growth in mice, which is a potential clinical treatment plan.

Mast cells-derived extracellular vesicles (EVs) play vital roles in various physiological and pathophysiological conditions. However, the cargoes of mast cells-derived EVs in asthma have not been established. Here, we set to identify the role of microRNA-21 (miRNA-21) from mast cells-derived EVs in ozone- and lipopolysaccharide (LPS)-induced mouse airway epithelial cells (MIC-iCell-a006 cells) and asthmatic mice.

After ozone or LPS treatment, MIC-iCell-a006 cells were subjected to a microarray analysis to screen differentially expressed miRNAs, and then co-cultured with EVs. miR-21 was silenced in cells, followed by CCK-8, scratch, and Transwell assays. Mice were challenged with ovalbumin, and antioxidant enzymes and inflammatory cell infiltration were assessed after EVs and miR-21 inhibitor treatments. The relation between miR-21 and DDAH1 was evaluated by Dual-luciferase assay, and changes in Wnt/β-catenin pathway related proteins were examined by western blot. Finally, the involvement of the DDAH1/Wnt/β-catenin axis in miR-21-mediated oxidative stress and inflammation was verified by rescue experiments.

miR-21 expression was upregulated in MIC-iCell-a006 cells induced by ozone or LPS. miR-21 was enriched in mast cells-derived EVs, and EVs increased miR-21 expression in MIC-iCell-a006 cells. miR-21 inhibitor increased cell activity and alleviated oxidative stress and inflammation. In asthmatic mice, miR-21 expression was increased, and EVs decreased antioxidant enzymes and increased inflammatory cells, whose effects were reversed by miR-21 knockdown. miR-21 targeted DDAH1 to mediate the Wnt/β-catenin signaling, and down-regulation of DDAH1 inhibited the action of miR-21 inhibitor.

The miR-21 secreted from mast cells-derived EVs promotes oxidative stress and inflammatory responses in asthmatic mice via the DDAH1/Wnt/β-catenin signaling axis.

The miR-21 secreted from mast cells-derived EVs promotes oxidative stress and inflammatory responses in asthmatic mice via the DDAH1/Wnt/β-catenin signaling axis.Mutation-activated Kras in cancer cells is a well-known challenging treatment-resistant factor that plays a critical role in treatment resistance. Human colorectal cancer (CRC) has four major Kras mutations; KrasG12D (34.2%), KrasG12V (21%), KrasG13D (20%) and KrasG12C (8.4%). Here, we report that while FL118 (a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX) exhibits high efficacy to kill CRC cells and eliminate CRC tumors, CRC cells/tumors with different Kras mutation subtypes in the defined p53/APC genetic statuses exhibit different sensitivity to FL118 treatment. Using CRC cell lines, SW620 (KrasG12V, mutant p53, mutant APC), DLD-1 (KrasG13D, wild type p53, mutant APC) and SNU-C2B (KrasG12D, mutant p53, wild type APC), we demonstrated that silencing of KrasG12V and KrasG12D using Kras-specific shRNA significantly increased CRC cell IC50, while silencing of KrasG13D decreased the CRC cell IC50. This finding suggests that both KrasG12V and KrasG12D are required for showing higher FL118 efficacy, while the presence of KrasG13D could somehow decrease FL118 efficacy under the defined p53/APC genetic status.