Laniersavage0690

In vivo, si-SIRT1 or SIRT1 overexpression in mice could enhance or rescue the inhibitory effects of rapamycin on tumor growth. In addition, SIRT1 transfection rescued the decreased level of phosphorylated (p)-PI3K, p-AKT and p-mTOR induced by rapamycin treatment. Taken together, the present results suggested that rapamycin suppressed the cell viability, migration, invasion and PI3K/AKT/mTOR signaling pathway in EC by negatively regulating SIRT1.The endoplasmic reticulum stress (ERS) response serves an important role in cerebral ischemia-reperfusion injury (CIRI). However, to the best of the our knowledge, the effect of rosuvastatin on the ERS response in CIRI has not yet been studied. In the present study, the effect of rosuvastatin on cell damage in CIRI was investigated; furthermore, the effect of rosuvastatin on the ERS response was explored. Firstly, a hypoxia/reoxygenation (H/R)-induced cell damage model was established in PC12 cells. Cell viability was subsequently detected by a Cell Counting Kit-8 assay. A lactate dehydrogenase kit was used to detect cytotoxicity. TUNEL assay was then used to measure the extent of cell apoptosis, and western blotting was used to analyze the expression levels of the apoptosis-associated proteins Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, western blotting was used to detect the expression levels of ERS-associated proteins, including phosphorylated (p)-protein kinase R-like endoplasmic reticulum kinase (PERK), p-eukaryotic initiation factor 2α and other proteins. Treatment with rosuvastatin led to an increased activity of H/R-induced PC12 cells and a decrease in their cytotoxicity. Rosuvastatin also led to an inhibition in apoptosis and ERS in H/R-induced PC12 cells. After administration of the ERS response activator thapsigargin (TG), TG was found to reverse the protective effect of rosuvastatin on injury of H/R-induced PC12 cells. Taken together, these findings have shown that rosuvastatin is able to protect PC12 cells from H/R-induced injury via inhibiting ERS-induced apoptosis, providing a strong theoretical basis for the use of rosuvastatin in the clinical treatment of CIRI.Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating interstitial lung disease. The origin of myofibroblasts is still to be elucidated and the existence of epithelial-mesenchymal transition (EMT) in IPF remains controversial. Hence, it is important to clarify the origin of fibroblasts by improving modeling and labeling methods and analyzing the differentiation pathway of alveolar epithelial cells (AEC) in pulmonary fibrosis with cell tracking technology. In the present study, adult transgenic mice with SPC-rtTA +/- /tetO 7 -CMV-Cre +/- /mTmG +/- were induced with doxycycline for 15 days. The gene knockout phenomenon occurred in type II AECs in the lung and the reporter gene cell membrane-localized enhanced green fluorescence protein (mEGFP) was expressed in the cell membrane. The expression of Cre recombinase and SPC was analyzed using immunohistochemical (IHC) staining to detect the labeling efficiency. A repetitive intraperitoneal bleomycin-induced pulmonary fibrosis model was established, and the mice were sacrificed on day 28. The co-localization of mEGFP and mesenchymal markers α-smooth muscle actin (α-SMA) and S100 calcium binding protein A4 (S100A4) were detected by multiple IHC staining. The results revealed that Cre was expressed in the airway and AECs in the lung tissue of adult transgenic mice with SPC-rtTA +/- /tetO 7 -CMV-Cre +/- /mTmG +/- induced by doxycycline; the labeling efficiency in the peripheral lung tissue was 63.27±7.51%. mEGFP was expressed on the membrane of type II AECs and their differentiated form of type I AECs. Expression of mEGFP was mainly observed in the fibrotic region in bleomycin-induced pulmonary fibrosis; 1.94±0.08% of α-SMA-positive cells were mEGFP-positive and 9.68±2.06% of S100A4-positive cells were mEGFP-positive in bleomycin-induced pulmonary fibrosis. In conclusion, the present results suggested that while EMT contributes to the pathogenesis of pulmonary fibrosis, it is not the major causative factor of this condition.Esophageal cancer is a malignant tumor type with one of the highest mortality rates worldwide. The aryl hydrocarbon receptor (AHR), which has been investigated in recent years, has been confirmed to be associated with the occurrence and development of esophageal cancer. AHR has a variety of different ligands, which regulate its activity following binding. The widely known acid inhibitor omeprazole (OME) also affects AHR and its downstream proteins (such as the cytochrome P450 family) by non-ligand binding; however, the mechanisms have remained to be fully elucidated. Therefore, the aim of the present study was to investigate the role of OME in esophageal squamous cell carcinoma (ESCC), whether the mechanism proceeds via the AHR pathway and how OME regulates AHR to affect the occurrence and development of esophageal carcinoma. The AHR-selective regulator OME was used to treat the ESCC cell lines TE1 and KYSE150. Western blot analysis was used to verify the effect of OME on AHR and proliferating cell nuclear antigen (PCNA) protein expression levels, while Cell Counting Kit (CCK)-8, wound-healing and Transwell assays were used to determine the proliferation, migration and invasion of the ESCCs, respectively, following treatment with OME. In addition, flow cytometry was used to investigate the cell cycle distribution of the ESCCs following incubation with OME. AHR was highly expressed in the ESCCs and following treatment with OME, the protein expression levels of AHR and PCNA were downregulated. The CCK-8 assay indicated that the proliferation of the ESCCs was also reduced following treatment with OME. Furthermore, flow cytometry revealed a notable block of the cells in G1/G0 phase, while the results of the wound-healing and Transwell assays respectively suggested that cell migration and invasion were reduced. In conclusion, OME inhibited the proliferation, migration and invasion of ESCC cells and blocked the cell cycle via the AHR pathway, which may provide a therapeutic effect on esophageal squamous cell cancer.Radiation therapy has been widely used for the treatment of various types of cancer; however, it may cause neuroinflammation during the pathological process of the disease. Astrocytes, the most abundant cell type in the central nervous system, have been confirmed to play vital roles in various diseases. Connexin (Cx)43, the main Cx type in astrocytes, which has been identified as a direct target gene of microRNA (miR)-206, was found to be involved in diseases pathologies in regions with astrocytes. The aim of the present study was to investigate the mechanism through which γ-radiation may cause astrocyte neuroinflammation and determine the specific mechanism underlying the effects of miR-206 in irradiation-induced HA-1800 cells. A dual-luciferase reporter system was used to predict and verify the target binding site between Cx43 and miR-206. HA-1800 cell viability and apoptosis were determined using a MTT assay and flow cytometry, respectively. In addition, the HA-1800 cells were induced by γ-radiation, then t43-plasmid transfected group. In addition, it was found that miR-206 mimics relieved irradiation-induced neuroinflammation, which was confirmed by increased cell viability, and reduced cell apoptosis and cleaved caspase-3 protein expression, as well as decreased inflammatory cytokine secretion. Furthermore, all the effects of miR-206 mimics on γ-radiation-induced astrocytes were reversed by Cx43-plasmid. In summary, the results of the present study indicated that miR-206 may relieve irradiation-induced neural damage by regulating Cx43, which may provide a novel research direction and a potential therapeutic target for the clinical treatment of inflammation-associated neuronal injury following irradiation.Increased levels of mitochondrial coupling factor 6 (CF6) are present in the peripheral blood of patients with preeclamptic pregnancies, and are particularly evident in cases of early-onset or severe preeclampsia. The present study examined the location and expression levels of CF6 in the placental tissue and its effect on the biological behavior of trophoblast cells. Placental tissue microarrays, including placental villous cytotrophoblast and extravillous cytotrophoblast microarrays, were used to detect the location and relative expression levels of CF6 in the placenta using immunohistochemistry. selleck chemical It was found that CF6 was expressed in both the normal and preeclamptic placenta, but its levels were higher in the preeclamptic tissues. In addition, the effects of the hypoxic environment on the biological behaviors of trophoblast cells were investigated in the JAR and JEG-3 cell lines. Following induction of hypoxia, the expression levels of CF6 were increased. Moreover, exogenous addition of human recombinant CF6 attenuated cell invasion, but exerted no effect on cell proliferation. At the molecular level, the expression levels of MMP-2 were decreased and were accompanied with a reduction in cell invasion following addition of exogenous CF6. In conclusion, the increased expression levels of CF6 and its effects in reducing the invasive abilities of trophoblast cells may be involved in the pathogenesis of severe preeclampsia.Cervical cancer (CC) is a type of gynecological malignancy that poses a significant threat to females. The aim of the present study was to examine the role of long intergenic non-protein coding RNA 1123 (LINC01123) and its underlying molecular mechanism in the development of CC. mRNA expression levels of LINC01123 and microRNA (miR)-361-3p in CC tissue samples and cell lines were evaluated using reverse transcription-quantitative PCR. Cell viability, migration and invasion were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing and Transwell assays. Moreover, a xenograft tumor model was established for elucidating the influence of LINC01123 knockdown on tumor growth in vivo. A dual-luciferase reporter assay was used to confirm the association between LINC01123 and miR-361-3p, and miR-361-3p and tetraspanin 1 (TSPAN1). Western blot analysis was used to determine TSPAN1 protein expression. LINC01123 expression was upregulated and miR-361-3p expression was reduced in CC tissue samples and cell lines. Knockdown of LINC01123 inhibited cell viability, migration and invasion in vitro, and suppressed tumor growth in vivo. Furthermore, LINC01123 targeted miR-361-3p and negatively regulated miR-361-3p expression. Overexpression of miR-361-3p inhibited cell viability, migration and invasion in HeLa and CaSki cells. Additionally, miR-361-3p targeted TSPAN1 and negatively regulated TSPAN1 expression. Inhibition of miR-361-3p and overexpression of TSPAN1 reversed the effect of LINC01123 knockdown on cell proliferation, migration and invasion in HeLa cells. Knockdown of LINC01123 inhibited cell proliferation, migration and invasion via miR-361-3p/TSPAN1 regulation in CC, which may present an effective target for treatment of CC.Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multisystemic involvement usually resulting from mutations in the tuberous sclerosis 1 (TSC1) or TSC2 genes. However, 10 to 25% of patients do not exhibit these mutations. Cerebral cavernous malformations (CCMs) are capillary-venous malformations that can be asymptomatic or cause variable neurological manifestations, including seizures. Familial CCMs are recognized. In both conditions, specific dermatological lesions are associated. We present the case of a 31-year-old female with TSC diagnosed at the age of 18 years who presented with negative genetic testing. She was admitted to our department in 2019 for a sudden increased frequency of focal seizures. Patient examination revealed multiple facial and intraoral angiofibroma, diplopia, right hemihypoesthesia, brisk deep tendon reflexes, and distal leg paresthesia. VideoEEG indicated a frontal paramedian epileptogenic focus. Cerebral magnetic resonance imaging (MRI) and angioMRI identified multiple fronto-parietal cortical tubers, as well as multiple CCMs, with evidence of bleeding in one.