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Orthopedic temporomandibular joint (TMJ) instability is very common among children and adults. It is often associated with pain in the cervicofacial region, and muscle contraction. To investigate whether muscle contraction can cause permanent posterior rotation of the head and whether treatment with splint and kinetotherapy is efficient, a literature review was carried out of patients with pain in the cervicofacial area. Additionally, the case of a 15-year old patient presenting with permanent posterior rotation of cra¬nium, with no movement between the first two vertebra and pain in the cervicofacial area was reported. Kinetotherapy followed by rapid maxillary expansion improved the function of cervical vertebrae and re¬duced the cervicofacial pain within the first two weeks. Kinetotherapy, rapid maxillary expansion, and or¬thodontic treatment with a stable joint position could be a good therapy to control occipital-atlas function.
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The aim of the multicentre study promoted by Nuova FIO is to evaluate the beneficial effects of the systemic Oxygen-Ozone (O2O3) therapy in patients suffering from SARS COV-2 disease in the early phases of the disease, before worsening, up to the need of tracheal intubation. The study is based on the rationale on that the systemic oxygen-ozone treatment could be effective, positively influencing the disease evolution and/or being able to mitigate the onset of the cytokine storm syndrome at least partially.
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Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.
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To investigate the role of microRNA-206 (miRNA-206) in the malignant progression of osteosarcoma and the underlying mechanism, expression pattern of miRNA-206 in osteosarcoma tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between miRNA-206 level and prognosis of osteosarcoma patients was analyzed. Regulatory effects of miRNA-206 on the proliferation and metastasis of U2OS and MG63 cells were evaluated by cell counting kit-8 (CCK-8), Transwell and wound healing assay. Through dual-luciferase reporter gene assay, the target gene of miRNA-206 was verified. A series of rescue experiments were conducted to explore the role of miRNA-206/Notch3 in regulating the malignant progression of osteosarcoma. MiRNA-206 was downregulated in osteosarcoma tissues and cell lines, and its level was correlated to poor prognosis and distant metastasis of osteosarcoma patients. Overexpression of miRNA-206 attenuated the proliferative and metastatic abilities of osteosarcoma cells, and miRNA-206 knockdown obtained the opposite trends. Notch3 was verified to be the target gene of miRNA-206, which was upregulated in osteosarcoma and accelerated osteosarcoma cells to proliferate and metastasize. Finally, rescue experiments showed that Notch3 overexpression partially reversed the regulatory effects of miRNA-206 on cellular behaviors of osteosarcoma cells. MiRNA-206 is downregulated in osteosarcoma. Overexpression of miRNA-206 accelerates osteosarcoma cells to proliferate and metastasize by targeting Notch3, thus accelerating the malignant progression of osteosarcoma.
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Previous reports indicated that specific cyclooxygenase-2 (COX-2) inhibitor suppresses osteoarthritis (OA). This study aimed to further explore the possible mechanism of Rofecoxib as a COX-2 inhibitor on the inhibition of chondrocyte (CH) hypertrophic development and tested the optimal treatment of Rofecoxib on CH. Basically, IL-1β was used as a stimulus to establish a degenerated CH model. Immunofluorescence, Western blot, and RT-PCR were performed to determine the gene expression of Axin2, β-catenin, GSK3β, collagen X, collagen II, COX-2, PGE-2, SOX-9, Runx-2, and MMP- 13 expression. Cell Counting Kit (CCK-8) assay was used to analyze the viability of CHs. The data indicated that Rofecoxib significantly inhibited COX-2 expression and had less harmful effects on CH viability. Rofecoxib reversed the IL-1β-induced upregulation of collagen X, COX-2, PGE-2, Runx-2, and MMP-13 expression, and promoted the viability of collagen II, SOX-9 expression of CHs. Furthermore, Rofecoxib suppressed Axin2, β-catenin, and GSK3β expression of the Wnt pathway, which was activated by IL-1β or human recombinant Wnt-1 protein treatment. Therefore, Rofecoxib is an effective COX-2 inhibitor that protects CHs from hypertrophy by suppression of the Wnt/β-catenin pathway.
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Breast cancer is one of the most common cancers in women. This study focuses on the effects of Long non-coding RNAs (lncRNAs) NNT-AS1 on breast cancer cell growth and metastasis. Fifty-six pairs of breast cancer (BC) tissues and matched paracarcinoma tissues were obtained. The BC cell lines and normal human breast cell line were employed. NNT-AS1 in BC cells was knocked down by shRNA. Cell counting kit-8 assay (CCK-8), colony formation assay, cell cycle analysis, cell apoptosis analysis, cound healing assay, Transwell assay, cioinformatics analysis, Western blot analysis and Xenograft model were used. Quantitative real-time polymerase chain reaction (qRT-PCR) assay indicated that expression of NNT-AS1 was obviously upregulated in breast cancer tissues compared with adjacent tissues (n=56). Knockdown of NNT-AS1 could attenuate breast cancer cell viability, proliferation, invasion and migration, as well as promote cell apoptosis and induce cell cycle arrest at G0/G1 phase. ZFP36 was directly combined with NNT-AS1, and silencing of ZFP36 could rescue tumor suppression role by downregulating NNT-AS1 on cell proliferation and metastasis. Knockdown of NNT-AS1 could suppress cell growth and metastasis via interacting with ZFP36 in vivo. This study demonstrated that knockdown of NNT-AS1 had tumor-suppressive effect on breast cancer progression and metastasis via interacting with ZFP36 in vitro and in vivo, which provides a new insight into the treatment and prognosis evaluation of breast cancer.
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The aim of the study was to explore the effect of lipoxin A4 (LXA4) on lung injury in sepsis rats through the p38/mitogen-activated protein kinase (MAPK) signaling pathway. Sprague-Dawley rats were used for the study. The rat model of sepsis-induced acute lung injury was established via cecal ligation (Sepsis group, n=20). LXA4 (0.1 mg/kg) was injected at 6 h after modeling (Treatment group, n=20), and a The Control group (n=20) was also set up. The 7-day survival rate was 100% in The Control group, and LXA4 raised the survival rate of rats in the Sepsis group from 40% to 60% (P<0.01). Alveolar fluid clearance (AFC) significantly declined and the wet/dry weight (W/D) ratio of lung tissues rose remarkably in the Sepsis group compared with those in the Control group, while LXA4 restored AFC and reduced the W/D ratio of lung tissues (P<0.05), suggesting that LXA4 treatment reduces lung fluids and partially enhances AFC, thus lowering the W/D ratio of lung. The total cell count, polymorphonuclear neutrophils (PMN) percentage and concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were obviously increased in the Sepsis group compared with those in the Control group, while they were markedly decreased in the Treatment group (P<0.05). The activity of myeloperoxidase (MPO) in lung tissue homogenate was evidently higher in the Sepsis group than that in The Control group, while it was notably lower in the Treatment group than that in the Sepsis group after LXA4 treatment (P<0.05). Moreover, it was observed microscopically that the morphology of lung tissues was intact in the Control group. Finally, the results of Western blotting manifested that the p-p38/ MAPK protein expression was remarkably increased in the Sepsis group, indicating the activation of the p38/MAPK pathway, while it was remarkably decreased in the Treatment group, indicating the inhibited activity of the pathway (P<0.05). LXA4 has an anti-inflammatory effect on sepsis rats with lung injury, and such effect is related to the p38/MAPK signaling pathway.
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The treatment for post-stroke depression (PSD) is mainly based on a therapeutic strategy combining anti-stroke and anti-depressant drugs. In the present study, the therapeutic effect of curcumin on rats with PSD was detected by open field tests and tail suspension tests, as well as the examination of corticosterone and corticotropin-releasing hormone (CRH) levels in the serum and neurotransmitter 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) levels in the hippocampus. Curcumin notably alleviated depression compared to the controls. Furthermore, long noncoding RNA growth arrest-specific transcript 5 (GAS5) enhanced by curcumin contributed to activation of the BDNF/Trkβ signaling pathway to promote the expression of synaptic-related proteins. GAS5 was demonstrated to function as a sponge of miR-10b. GAS5 upregulation by curcumin could reduce miR-10b to compromise the BDNF mRNA levels. Taken together, these results revealed a novel mechanism of curcumin on PSD through the GAS5/miR-10b/BDNF regulatory axis.
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Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. MicroRNAs (miRNAs/miRs) have been reported to play significant roles in the progression of human tumors, however, the expression and biological role of miR-23b in NSCLC remains elusive. Underexpression of miR-23b was detected in NSCLC tissues in comparison with the matched para-carcinoma tissues. The clinical value of miR-23b was analyzed, and the findings showed that miR-23b expression was negatively correlated with poor overall survival and malignant clinicopathologic characteristics of NSCLC patients. Furthermore, functional assays demonstrated that overexpression of miR-23b inhibited NSCLC cell viability, invasion and migration. Luciferase reporter assay and qRT-PCR revealed that RUNX2 was a functional target of miR-23b. The elevated expression of RUNX2 was positively correlated with overall survival of NSCLC patients. Additionally, Western blot analysis indicated that EMT and Wnt/β-catenin pathways were blocked by the upregulation of miR-23b. Taken together, these data demonstrated that dysregulation of miR-23b/RUNX2 signal may be a novel therapeutic target for the treatment of NSCLC.
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Fibroblast-like synoviocytes (FLSs) exert a critical effect in the occurrence and progress of rheumatoid arthritis (RA). MicroRNA-495 (miR-495) can regulate many growth behaviors in various cell types. Nevertheless, the role of miR-495 is still unclear in RA-FLS. We aimed to explore the role and molecular mechanism of miR-495 in RA. The FLSs and synovial tissue from normal and RA cases were used in the study. RT-PCR analysis was used to examine the expression of miR-495. Western blot assay was conducted to determine the levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and β-catenin. Cell counting kit-8 (CCK-8) assays were performed to determine the proliferation of RA-FLS in different treatment groups. The results showed that miR-495 is down-regulated in both RA-synovial tissue and RA-FLSs. Overexpression of miR-495 could inhibit RA-FLS proliferation and inflammatory factors of interleukin (IL)-6, IL-11 and tumor necrosis factor alpha (TNF-α), and decrease the protein expression of MMP-9 and MMP-2. In addition, miR-495 could negatively regulate the expression of β-catenin in RA-FLSs. We also confirmed that the inhibitory role of miR-495 in RA-FLS is through the regulation of β-catenin expression. Taken together, miR-495 is downregulated in RA-FLS and RA synovial tissue, and miR-495 inhibits proliferation and inflammatory response in RA-FLS, partially via regulating β-catenin expression. The miR-495/β-catenin pathway may serve as a new therapeutic target for RA.
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Sigma-1 receptor (Sig-1R) is a ligand-operated protein that modulates activity of various proteins. It is expressed within the endoplasmic reticulum membranes of multiple organs. We examined the role of Sig-1R in hepatic ischemia-reperfusion injury (IRI). We studied IRI indicators in Sig-1R-/- mice and compared them with wild-type controls. In addition, we assessed the influence of Sig-1R agonist, fluvoxamine, on IRI in both types of animals. We found that Sig-1R-/- mice exhibited significantly decreased liver damage after hepatic IRI as compared to wild-type mice. This effect was manifested by decreased serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), myeloperoxidase (MPO), and supernatant level of lactate dehydrogenase (LDH), decreased endothelial glycocalyx shedding indexed by decreased serum levels of heparan sulfate and syndecan-1, slightly improved liver histology and reduced metalloproteinase-9 expression. Furthermore, in comparison to Sig-1R-/- mice, fluvoxamine significantly increased serum levels of AST, ALT, MPO, and LDH in wildtype animals in a dose-dependent manner at 6 h after IRI. Our findings demonstrate that the absence of Sig-1R provides a protective effect during hepatic IRI. Sig-1R-mediated signaling pathways may play distinct roles in IRI in different organs. The dynamic interaction between Sig-1R and other signaling molecules in different organs needs to be examined further.
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Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and Western blot assays were conducted to detect GPRIN1 expression in lung cancer cells and normal control cells. To detect the functional effects of knockdown/overexpression of GPRIN1 on lung cancer cells, we performed CCK-8, colony formation and Transwell assays. Through the Kaplan-Meier method, we found that GPRIN1 expression correlated with overall survival and adverse prognosis, and Cox regression indicated that GPRIN1 is as an independent predictive factor for lung adenocarcinoma. Furthermore, the mRNA and protein expression levels of GPRIN1 in lung cancer cells were markedly higher than those in normal cells. Downregulation of GPRIN1significantly decreased cell viability, colony formation, the number of invasive and migrating cells, and levels of epithelial-mesenchymal transition-related proteins in A549 cells. Overexpression of GPRIN1showed the opposite effect in Calu-1 cells. Together, these results indicated that GPRIN1 facilitates lung cancer proliferation and migration, possibly by affecting the epithelial-mesenchymal transition of lung cancer cells, suggesting that GPRIN1may be used as an effective target for the treatment of lung cancer
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The object of this study was to explore the effect of rapamycin regulating the proliferation of Schwann cells through activating the extracellular signal-regulated kinase (ERK) signaling pathway on rats with spinal cord injury (SCI). The rat Schwann cells were cultured and divided into solvent (DMSO) group, rapamycin (Rapa) group (1.5 nM, 3.0 nM, 6.0 nM, 12.0 nM, 24.0 nM and 48.0 nM), and Rapa + ERK inhibitor (PD98059) group (40 mM). The proliferation of Schwann cells was detected by MTS. Western blot was used to evaluate the expression of ERK and p-ERK protein. Moreover, the spinal cord compression injury rat model was established, and the rats were divided into normal control group, SCI group and Schwann cell transplantation group. The animal experiment ended 7 weeks after Schwann cells had been injected every day into the injured rats. In the second animal experiment, the rats were divided into DMSO group, Rapa group and Rapa + PD98059 group. The motor recovery of rats was evaluated using the Basso-Beattie-Bresnahan (BBB) score every week, and the proliferation of Schwann cells at the site of SCI was detected using immunohistochemistry. It was verified that lowdose rapamycin (1.5 nM) could significantly promote the proliferation of Schwann cells cultured in vitro (P>0.001), most significantly at 48 h. Rapamycin could activate the ERK signaling pathway. The results of the first animal experiment showed that the BBB score in Schwann cell transplantation group rose with time compared with that in SCI group (P>0.05). The BBB score was obviously increased in Rapa group compared with that in DMSO group and Rapa + PD98059 group (P>0.05). According to the results of Ki67 immunohistochemistry, the proliferation ability of Schwann cells at the site of SCI was remarkably stronger than that in the other two groups. Rapamycin regulates the proliferation of Schwann cells through the ERK signaling pathway. The proliferation of Schwann cells can effectively repair the damaged nerve cells and neurological function in SCI rats
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Gallbladder cancer (GBC) is a malignant tumors that develops insidiously and rapidly. In this work, we explored the function of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) in modulating GBC development. PVT1 and miR-30d-5p expression were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The relationship of PVT1 and miR-30d-5p was analyzed by Dual luciferase activity and Spearman correlation analysis. The effect of PVT1 on GBC progression was detected by cell counting kit-8 (CCK-8) and Transwell assay. In GBC tissues and cell lines, upregulation of PVT1 and downregulation of miR-30d-5p were observed. PVT1 silencing suppressed cell proliferation and invasion of GBC cells. Based on the analysis of Dual luciferase activity and Spearman correlation, miR-30d-5p was confirmed as a target of PVT1, and their expression had a negative correlation in GBC tissues. Additionally, miR-30d-5p inhibitor could reverse the effects of PVT1 knockdown. These data demonstrated that PVT1 facilitated to GBC tumorigenesis by promoting cell proliferation and invasion via miR-30d-5p, indicating that PVT1 may be a potential biomarker of GBC diagnosis and treatment.
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We aimed to elucidate the inhibitory effect of Baicalein on proliferative ability in Prostate cancer (PCa) through downregulating Ezrin. Relative level of Ezrin in PCa tissues and adjacent ones was detected. After PC3 cells were induced with 20 or 40 μM Baicalein, changes in viability, cell cycle progression and apoptosis were assessed. Relative levels of CyclinD1, CDK4, P53 and P21 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of Ezrin and Baicalein treatment on PC3 cells were evaluated. Finally, in vivo effects of Ezrin and Baicalein treatment on nude mice bearing PCa were detected. Ezrin was upregulated in PCa tissues relative to adjacent normal ones. Baicalein treatment decreased viability, arrested cell cycle and stimulated apoptosis in PC3 cells. Meanwhile, Baicalein treatment downregulated CyclinD1 and CDK4, while upregulating P53 and P21. Moreover, Ezrin was downregulated in Baicalein-treated PC3 cells. Knockdown of Ezrin synergistically stimulated the effects of Baicalein on cellular phenotypes of PC3 cells. In nude mice bearing PCa, Baicalein treatment decreased tumor volume and tumor weight, which were much more pronounced in those with in vivo knockdown of Ezrin. Baicalein treatment suppresses proliferative ability, arrests cell cycle and stimulates apoptosis in PCa cells through downregulating Ezrin.
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Previous studies have shown that lncRNAs play crucial roles in cerebral ischemia/reperfusion injury. In this study, the function and possible mechanism of lncRNA HCP5 in cerebral ischemia/reperfusion injury was investigated. An oxygen glucose deprivation (OGD) model in N2a cells was used to simulate cerebral ischemia/reperfusion injury in vitro. The functional mechanism of lncRNA HCP5 was detected using Trypan blue staining, JC-1, MTT and dual luciferase reporter assays. The expression of apoptosis-related proteins (Bcl-2 and Bax) was measured by Western blot analysis. We found that lncRNA HCP5 was upregulated in N2a cells treated with OGD/R, and knockdown of lncRNA HCP5 enhanced cell viability and reduced cell death. In addition, miR-652-3p was found to act as a sponge for lncRNA HCP5. The overexpression of miR- 652-3p can prevent cerebral ischemic reperfusion injury, however, lncRNA HCP5 attenuated the protective effect of miR-652-3p in cerebral ischemic reperfusion injury. In conclusion, upregulation of lncRNA HCP5 may exacerbate cerebral ischemic reperfusion injury by sponging miR-652-3p.
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The aim of this study was to elucidate the neuronal protection effect of sodium butyrate (NaB) on neuronal apoptosis in rats with cerebral infarction (CI), and the involvement of the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways. MI model in rats was performed by middle cerebral artery occlusion (MCAO). Three hours after reperfusion, gastric administration of 5 or 10 mg/kg NaB was performed. Neurological deficit score, infarct size and brain edema were evaluated in rats after 24 h of reperfusion. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine contents of oxidative stress factors. Lactate dehydrogenase (LDH) activity, cell viability and apoptosis in extracted neurons were determined. Moreover, expression levels of Bcl-2, Bax, Akt and ERK1/2 were examined. NaB treatment markedly reduced infarct size and brain edema content in CI rats, and NaB treatment improved viability, decreased LDH activity and reversed contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in a dose-dependent manner. In addition, NaB treatment dose-dependently reduced apoptotic rate and Bax level, as well as enhanced Bcl-2 level. Protein levels of Akt and ERK1/2 were markedly upregulated in NaB-treated neurons. NaB treatment alleviates neuronal apoptosis via the PI3K/Akt and ERK1/2 pathways in CI rats, thus protecting the deterioration of CI
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Accepted as crucial participators in human diseases, microRNAs (miRNAs) have been demonstrated to play important roles in cancer progression, including hepatocellular carcinoma (HCC). The purpose of this study is to preliminarily elucidate the role of miR-369-3p in HCC. Here, miR-369-3p and PAX6 expressions were detected by RT-qPCR. The functional mechanism of miR-369-3p/PAX6 axis was investigated by MTT, Transwell and luciferase reporter assays. The results showed that miR- 369-3p was downregulated in HCC and was associated with lymph node metastasis and TNM stage in HCC patients. Functionally, miR-369-3p overexpression inhibited cell viability and motility in HCC. Furthermore, PAX6 was confirmed as a direct target of miR-369-3p, and upregulation of PAX6 exerts carcinogenesis in the development of HCC. PAX6 can weaken the inhibitory effect of miR-369-3p in HCC. In conclusion, miR-369-3p inhibits the proliferation, migration and invasion of HCC cells by suppressing PAX6 expression.
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This article aims to explore the expression and mechanism of miR-10a-5p in pancreatic cancer. MiR-10a-5p mimic, MiR-10a-5p inhibitor and negative control were transfected into human pancreatic cancer cell line SW1990. Real-time quantitative PCR technology was used to analyze the expression level of miR-10a-5p in pancreatic cancer tissues and cells. The proliferation, invasion and apoptosis of SW1990 cells in each group were detected by CCK-8 analysis, Transwell analysis, TUNEL method and flow cytometry. Targetscan7.2 was used to predict the target protein of MiR-10a-5p, and the expression of related proteins was detected by Western blot analysis. The results showed that the expression of miR- 10a-5p in cancer tissues of patients with pancreatic cancer was significantly higher than that in adjacent tissues (P < 0.05). The expression of miR-10a-5p in cancer cells increased significantly, which could promote the proliferation and invasion of SW1990 cells and inhibit apoptosis (P < 0.05). Overexpression of miR-10a-5p can regulate the expression of BDNF and SEMA4C. miR-10a-5p can promote the occurrence and development of pancreatic cancer by regulating the BDNF / SEMA4C pathway, and may become a molecular target for the diagnosis and treatment of pancreatic cancer in the future.
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The purpose of this study was to investigate the effect of desflurane (Des) pretreatment on sepsisevoked lung injury in rats and its mechanism. The rat model of sepsis-evoked lung injury was prepared using lipopolysaccharide (LPS), while rat lung mesenchymal cell (MSC) model was cultured in vitro, followed by Des pretreatment or inhibitor S31-201 culture. The degree of lung tissue injury was analyzed by Hematoxylin-eosin (HE) staining. The expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in the serum of rats were detected by enzyme-linked immunosorbent assay (ELISA). One-step terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was utilized to determine the apoptosis levels of lung tissues and MSCs cultured in vitro. The expressions of the signal transducer and activator of transcription 3 (STAT3) pathway in rat lung tissues and MSCs were detected by Western blotting. After modeling, LPS induced the lung injury in rats, the expression levels of IL-6, IL-1β and TNF-α were up-regulated (P<0.05), the apoptosis rate was increased (P<0.05), and phosphorylated-Janus kinase 2 (p-JAK2) and phosphorylated-STAT3 (p-STAT3) protein expressions were up-regulated (P<0.05). Des pretreatment can alleviate LPS-induced lung injury, down-regulate IL-6, IL-1β and TNF-α expression levels (P<0.05), reduce apoptosis (P<0.05), and downregulate p-JAK2 and p-STAT3 protein levels (P<0.05). LPS induced an increase in apoptosis rate of MSCs (P<0.05) and the up-regulation of p-STAT3 protein expression (P<0.05). Both Des pretreatment and S31-201 inhibitor culture could reduce the apoptosis rate (P<0.05) and down-regulate p-STAT3 protein level (P<0.05). Des pretreatment can reduce sepsis-evoked lung injury in rats, which may be related to the inhibition of protein expressions of STAT3 pathway.
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This study aims to investigate the role of PM2.5 exposure in inducing apoptosis of alveolar epithelial cells and thereafter emphysema in mice, and the underlying mechanism. PM2.5 exposure model in mice was constructed. Lung tissues were harvested from healthy mice and model mice for hematoxylin and eosin (H&E) staining. Protein levels of Forkhead box O3 (FOXO3A) and BIM in lung tissues were detected by Western blot. Subsequently, A549 cells were induced with increased doses of PM2.5, followed by determination of relative levels of FOXO3A, BIM (Bcl-2 interacting mediator of cell death) and clv-caspase3. Apoptosis in PM2.5-exposed A549 cells was assessed. Chromatin immunoprecipitation (ChIP) assay was conducted to uncover the interaction between FOXO3A and BIM. Finally, regulatory effects of FOXO3A/BIM on apoptosis of A549 cells were determined. PM2.5 exposure resulted in expansion of alveolar spatial structure and decline of lung function, thus leading to emphysema in mice. Protein levels of FOXO3A and BIM were markedly upregulated in lungs of model mice. Relative levels of FOXO3A, BIM and clv-caspase3 were enhanced in PM2.5 -exposed A549 cells, which were reversed by transfection of si-FOXO3A. ChIP assay confirmed that FOXO3A was able to regulate BIM transcription through binding its promoter regions. Importantly, regulatory effects of FOXO3A on apoptosis of PM2.5 -exposed A549 cells were partially reversed by overexpression of BIM. PM2.5 exposure leads to upregulation of FOXO3A, which triggers BIM transcription, thus inducing apoptosis of alveolar epithelial cells and emphysema in mice.
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NIn recent years, the incidence of diabetic nephropathy (DN) is rising, and is one of the most important complications of diabetic patients. In this study, the role and regulatory mechanism of lncRNA OIP5-AS1 in the regulation of DN were investigated. Here, the expressions of lncRNA OIP5-AS1 and miR-30c-5p were detected by RT-qPCR. Western blot analysis was used to detect the protein expression of E-cadherin, N-cadherin, TGF-β1, α-SMA. The relationship between OIP5-AS1 and miR-30c-5p was confirmed by dual luciferase reporter assay. The results showed that the expression of lncRNA OIP5-AS1 was increased in db/db DN mice kidney tissue and high glucose-stimulated HK2 cells. lncRNA OIP5-AS1 promoted epithelial-to-mesenchymal transition (EMT) and renal fibrosis in high glucose-stimulated HK2 cells. In addition, lncRNA OIP5-AS1 directly targets miR-30c-5p, and lncRNA OIP5-AS1 negatively regulated miR-30c-5p expression in high glucose-stimulated HK2 cells. More importantly, overexpression of miR-30c-5p attenuated the promoting effect of OIP5-AS1 on EMT and renal fibrosis in high glucose-stimulated HK2 cells. In conclusion, lncRNA OIP5-AS1 induces EMT and renal fibrosis in DN via binding to miR-30c-5p.
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The purpose of this study was to explore the effect of the Jinrong granule on CXCL-1 and the mechanism of the Jinrong granule on the metastasis and apoptosis of breast cancer cell lines. MDA-MB-231 human breast cancer cell line was divided into a control group, Jinrong extract group, CXCL-1 group and Jinrong extract + CXCL-1 group. The proliferation, apoptosis and permeability of the cells in the experimental group were studied. The protein expression of CXCL-1 was detected by Western blot. On this basis, a bioinformatics method was used to analyze the mechanism of CXCL-1. The results of the CCK8 experiment showed that compared with the control group, the cell proliferation activity of the CXCL-1 treatment group was enhanced while that of the Jinrong granule group was decreased. Compared with that of the CXCL-1 treatment group, the cell proliferation rate of the CXCL-1 + Jinrong granule group was significantly lower. The results showed that CXCL-1 could inhibit apoptosis of breast cancer cells, while the Jinrong granule could reverse the inhibition of apoptosis induced by CXCL-1. The results showed that the Jinrong granule could inhibit the ability of CXCL-1 to promote the migration and proliferation of breast cancer cells. The Jinrong granule could reverse the promoting effect of CXCL-1 on breast cancer through the CXCL-1- CLCR2/CCL20 pathway. In conclusion, the Jinrong granule can inhibit the invasion of breast cancer cells through the CXCL-1-CLCR2/CCL20 pathway.
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Chlamydia trachomatis, the leading cause of bacterial sexually transmitted diseases worldwide, can disseminate and localize to the upper genital tract impairing reproductive function. Specifically, ascending C. trachomatis genital infection has been demonstrated to cause epididymitis or epididymo-orchitis, well-known risk factors for male infertility. C. trachomatis possesses the ability to infect primary human Sertoli cells, key elements for the spermatogenetic process and the immune protection of germ cells. Therefore, herein, we investigated the innate immune response in Sertoli cells following C. trachomatis infection, as well as its indirect effects on human spermatozoa. Specifically, we evaluated C. trachomatis mediated induction of Toll-like Receptors (TLR) 2, 3 and 4 as well as of downstream intracellular signaling molecules (NFκB and IRF3) and the levels of the related inflammatory mediators (IL-1α, IL-6, IFN-α, IFN-β and IFN-γ), in an in vitro infection model of primary human Sertoli cells. The main result of our study shows that C. trachomatis induced TLR3-mediated recognition in human Sertoli cells, accompanied by the down-modulation of NFκB and IRF3-dependent signaling pathways followed by no production of pro-inflammatory cytokines. In conclusion, our findings suggest that C. trachomatis can disrupt the innate immune response in Sertoli cells and evade intracellular killing, potentially giving rise to a long-term infection that may exert negative effects on the male reproductive system.
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Macrophages have been reported to participate in inflammation, tissue homeostasis and tissue repair. The detailed mechanism of macrophage-mediated tissue repair is not clear. CXCL-10, secreted by monocytes, endothelial cells and fibroblasts, mediates immune response and angiogenesis by binding to CXCR3. In this study, the expression of CXCL-10 and CXCR3 in porcine lung injury induced by porcine reproductive and respiratory syndrome virus (PRRSV) infection was firstly examined. The results showed that the expression of both CXCL-10 and CXCR3 increased in the infected pig lungs. In addition, the increased expression of CXCL-10 and CXCR3 in macrophage treated by poly (I:C) was also observed, suggesting the autocrine system existed in macrophages. Furthermore, CXCL-10 treatment induced upregulation of Arg1 and VEGFa, and downregulation of TNFα in macrophage, and CXCR3 antagonist AMG487 treatment presented the contrary effects on the expression of Arg1, VEGFa, and TNFα. CXCL- 10-stimulated effects were dependent on PI3K/Akt signaling pathway. Wound-healing assay showed that CXCL-10 treatment macrophage conditioned medium promoted the healing process of endothelial cells. Our results suggested that CXCL-10/CXCR3 in macrophage may mediate tissue repair by regulating the macrophage expression of Arg1, VEGFa and TNFα. Modulation of CXCL-10/CXCR3 axis in macrophage may be a potential therapeutic strategy for tissue injury and repair.
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