UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway.

BACKGROUND: Ubiquilin-4 (UBQLN4), a member of the ubiquilin family, has received limited attention in cancer research to date. Here, we investigated for the first time the functional role and mechanism of UBQLN4 in non-small cell lung cancer (NSCLC). METHODS: The Cancer Genome Atlas (TCGA) database was employed to validate UBQLN4 as a differentially expressed gene. Expression differences of UBQLN4 in NSCLC cells and tissues were assessed using immunohistochemistry (IHC) experiment and western blotting (WB) experiment. Kaplan-Meier analysis was conducted to examine the association between UBQLN4 expression and NSCLC prognosis. Functional analyses of UBQLN4 were performed through cell counting kit-8 (CCK-8), colony formation, and transwell invasion assays. The impact of UBQLN4 on tumor-associated signaling pathways was assessed using the path scan intracellular signaling array. In vivo tumorigenesis experiments were conducted to further investigate the influence of UBQLN4 on tumor formation. RESULTS: UBQLN4 exhibited up-regulation in both NSCLC tissues and cells. Additionally, over-expression of UBQLN4 was associated with an unfavorable prognosis in NSCLC patients. Functional loss analyses demonstrated that inhibiting UBQLN4 could suppress the proliferation and invasion of NSCLC cells in both in vitro and in vivo settings. Conversely, functional gain experiments yielded opposite results. Path scan intracellular signaling array results suggested that the role of UBQLN4 is associated with the PI3K/AKT pathway, a correlation substantiated by in vitro and in vivo tumorigenesis experiments. CONCLUSION: We validated that UBQLN4 promotes proliferation and invasion of NSCLC cells by activating the PI3K/AKT pathway, thereby facilitating the progression of NSCLC. These findings underscore the potential of targeting UBQLN4 as a therapeutic strategy for NSCLC.

Curcumin Promotes Diabetic Foot Ulcer Wound Healing by Inhibiting miR-152-3p and Activating the FBN1/TGF-ß Pathway.

The objective of this study was to investigate the mechanism of curcumin in diabetic foot ulcer (DFU) wound healing. A DFU rat model was established, and fibroblasts were cultured in a high-glucose (HG) environment to create a cell model. Various techniques, including Western blot, RT‒qPCR, flow cytometry, Transwell, cell scratch test and H&E staining, were employed to measure the levels of relevant genes and proteins, as well as to assess cell proliferation, apoptosis, migration, and pathological changes. The results showed that miR-152-3p was overexpressed in DFU patients, while FBN1 was underexpressed. Curcumin was found to inhibit fibroblast apoptosis, promote proliferation, migration, and angiogenesis in DFU rats, and accelerate wound healing in DFU rats. In addition, overexpression of miR-152-3p weakened the therapeutic effect of curcumin, while overexpression of FBN1 reversed the effects of the miR-152-3p mimic. Further investigations into the underlying mechanisms revealed that curcumin expedited wound healing in DFU rats by restoring the FBN1/TGF-ß pathway through the inhibition of miR-152-3p. In conclusion, curcumin can suppress the activity of miR-152-3p, which, in turn, leads to the rejuvenation of the FBN1/TGF-ß pathway and accelerates DFU wound healing.

Radial extracorporeal shock wave therapy alleviates acute inflammation of human primary tenocytes through the integrin-FAK-p38MAPK pathway.

OBJECTIVES: To explore whether radial extracorporeal shock wave therapy (rESWT) can alleviate acute inflammation of human primary tenocytes by the integrin-focal adhesion kinase (FAK)-p38 mitogen-activated protein kinase (MAPK) pathway. METHODS: Western blotting was used to evaluate the changes in the integrin-FAK-p38MAPK signaling pathway mediated by rESWT using specific antibodies targeting the phosphorylation sites of intracellular signal pathway proteins. RESULTS: rESWT up-regulated FAK phosphorylation and down-regulated p38MAPK phosphorylation levels in a tumor necrosis factor (TNF)-α-induced acute inflammation model of human primary tenocytes. Pretreatment with an integrin inhibitor significantly reduced rESWT-mediated downregulation of p38MAPK phosphorylation and attenuated its reversal effect on the increased secretion of pro-inflammatory cytokines in TNF-α-induced human primary tenocytes. CONCLUSIONS: Our results imply that rESWT may partially alleviate acute inflammation in human primary tenocytes through the integrin-FAK-p38MAPK pathway.

Silencing LINC00491 Inhibits Pancreatic Cancer Progression through MiR-188-5p-induced Inhibition of ZFP91.

Background: Pancreatic cancer is recognized as one of the most malignant tumors with poor prognosis. Recently, long noncoding RNAs (lncRNAs) are considered as a potential prognostic biomarker of PC. However, the concrete biological effect of lncRNAs in PC remains unmasked. Herein, we explored the mechanism of LINC00491 in PC. Methods: Quantitative real-time PCR (qRT-PCR) was administrated to detected the expression of LINC00491 in PC tissues and cell lines. Loss-of-function experiment in vitro and in vivo was carried out to figure out the biological effects of LINC00491 on PC carcinogenesis. Luciferase reporter assay, subcellular fractionation, western blotting, pull-down assay and RNA immunoprecipitation assay were further used to explore the mechanism of PC tumorigenesis of LINC00491. Results: An increase of LINC00491 was detected in PC cell lines and tissues. Silencing LINC00491 in vitro and in vivo subsequently hindered cell migration, invasion, proliferation and tumor growth, respectively. Further research confirmed a negative and a positive connection of LINC00491 with microRNA 188-5p (miR-188-5p) level and Zinc finger protein 91 (ZFP91), a target of miR-188-5p, respectively. qRT-PCR and western blotting found that miR-188-5p was upregulated while LINC00491 was downregulated, concomitant with ZFP91 decreasing in PC cells or node mouse tumors, which could be significantly restored by inhibiting miR-188-5p. Besides, overexpression of miR-188-5p partially restored the inhibitory effect of LINC00491 diminution on proliferation, migration, and invasion of PC cells. Conclusion: LINC00491 promotes PC proliferation, migration, invasion via the miR-188-5p/ZFP91 axis, suggesting LINC00491 could be a new therapeutic target for PC.

LINC01128 facilitates the progression of pancreatic cancer through up-regulation of LDHA by targeting miR-561-5p.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate tumor development and metastasis in several types of cancers through various molecular mechanisms. However, the biological role of most lncRNAs in pancreatic cancer (PC) remains unclear. Here, we explored the expression, biological functions, and molecular mechanism of LINC01128 in PC. METHODS: Quantitive reverse transcription PCR was used to detect the expression level of LINC01128 in PC tissues and different PC cell lines. A loss-of-function and gain-of-function experiment was used to explore the biological effects of LINC01128 on PC carcinogenesis in vitro and in vivo. Western blot analysis, subcellular fractionation experiment, luciferase reporter gene assay, and MS2-RNA immunoprecipitation experiment were used to study the potential molecular mechanism of LINC01128 during carcinogenesis. RESULTS: The expression of LINC01128 was upregulated in PC tissues and cell lines, and overexpression of LINC01128 was significantly related to the poor prognosis of patients with PC. Furthermore, silencing LINC01128 significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of PC cells in vitro and tumor growth in vivo, while LINC01128 overexpression promoted these processes. Further research showed that LINC01128 acted as a sponge for microRNA miR-561-5p, and lactate dehydrogenase A (LDHA) was the downstream target gene of miR-561-5p. It was also revealed that the expression of miR-561-5p in PC was decreased, and a negative correlation between miR-561-5p and LINC01128 was revealed. Based on rescue experiments, LDHA overexpression partially restored the inhibitory effect of LINC01128 knockdown on proliferation, migration, and invasion of PC cells. CONCLUSIONS: LINC01128 promotes the proliferation, migration, invasion, and EMT of PC by regulating the miR-561-5p/LDHA axis, suggesting LINC01128 may be a new prognostic marker and therapeutic target in PC.

Long non-coding RNA LINC01224 promotes progression and cisplatin resistance in non-small lung cancer by sponging miR-2467.

Copious evidence reveals that long non-coding RNAs (lncRNAs) exert great regulatory functions in various human cancers. LINC01224 is a novel lncRNA, identified as a cancer regulator of HCC. However, the underlying mechanisms and clinical significance of LINC01224 in other types of cancers need further researches to explore. In this study, we aimed to elucidate the biological role of LINC01224 in NSCLC progression. Presently, LINNC01224 expression was elevated and miR-2467 expression was down-regulated in NSCLC, compared with standard control. Then we described the reciprocal correlation between LINC01224 and miR 2467. Afterward, the dual-luciferase reporter assay, RIP assay and RNA pull-down assay validated the base-pair interaction between LINC01224 and miR-2467. Moreover, our findings demonstrated that the silence of LINC01224 inhibited cell proliferation and invasion in NSCLC and enhanced cisplatin (CDDP) sensitivity in vitro. Besides, rescue assays verified that miR-2467 inhibitor could reverse the effects on cell biological activities and CDDP resistance caused by knockdown of LINC01224. Finally, in vivo experiments implicated that knockdown of LINC01224 could inhibit NSCLC tumor growth. To sum up, LINC01224 can promote tumor progression and CDDP resistance in NSCLC via sponging miR-2467, suggesting a promising therapeutic target for better diagnosis and prognosis of NSCLC patients.

Discovery of a novel 112-type iron-pnictide and La-doping induced superconductivity in Eu1-xLaxFeAs2 (x=0-0.15).

We report the discovery and characterization of a novel 112-type iron pnictide EuFeAs2, with La-doping induced superconductivity in a series of Eu1-xLaxFeAs2. The polycrystalline samples were synthesized through solid state reaction method only within a very narrow temperature window around 1073K. Small single crystals were also grown from a flux method with the size about 100µm. The crystal structure was identified by single crystal X-ray diffraction analysis as a monoclinic structure with space group of P21/m. From resistivity and magnetic susceptibility measurements, we found that the parent compound EuFeAs2 shows distinct anomalies probably due to the Fe2+ related antiferromagnetic/structural phase transition near 110K and the Eu2+ related antiferromagnetic phase transition near 40K. La-doping suppressed both phase transitions to lower temperatures and induced superconducting transitions with a Tc∼11K for Eu0.85La0.15FeAs2.

Isoflurane protects against injury caused by deprivation of oxygen and glucose in microglia through regulation of the Toll-like receptor 4 pathway.

Oxygen and glucose deprivation (OGD) are the most important factors related to tissue damage resulting from stroke. Microglial cells have been found to be very vulnerable to ischemia and OGD. It has been reported that isoflurane exposure can protect the mammalian brain from insults such as ischemic stroke; however, the effects of isoflurane on OGD-induced injury in microglia are as yet unknown. In this study, we investigated the effects of isoflurane on OGD-induced injury in microglia. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) revealed that OGD did indeed induce cell death in microglia. However, isoflurane preconditioning attenuated OGD-induced cell death. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated that isoflurane treatment alleviated OGD-induced apoptosis. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. Our results indicate that isoflurane preconditioning inhibits the upregulation of TLR4 as well as the activation of its downstream molecules, such as c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB), in BV-2 microglia exposed to OGD. Importantly, we also found that isoflurane pretreatment significantly reduces the production of proinflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-ß, and nitric oxide (NO). The results indicate that TLR4 and its downstream NF-κB-dependent signaling pathway contribute to the neuroprotection of microglia exposed to OGD/reoxygenation by administration of isoflurane.