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The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.
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Coronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1β which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1β which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Rα receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2. The suppression of IL-1β by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1β and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy.
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SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation "breaks down" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.
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CoV-19/SARS-CoV-2 is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19) an acute respiratory distress syndrome which provokes serious problems for global health. Studies suggest that there are many differences between men and women in the immune response to CoV-19 infection and inflammatory diseases. Women, compared to men, are less susceptible to viral infections based on a different innate immunity, steroid hormones and factors related to sex chromosomes. The presence of two X chromosomes in women emphasize the immune system even if one is inactive. The immune regulatory genes encoded by X chromosome in female gender causes lower viral load levels, and less inflammation than in man, while CD4+ T cells are higher with better immune response. In addition, women generally produce higher levels of antibodies which remain in the circulation longer. The levels of activation of the immune cells are higher in women than in men, and it is correlated with the trigger of TLR7 and the production of IFN. TLR7 is higher in women than in men and its biallelic expression leads to higher immune responses and increases the resistance to viral infections. TLR7 is expressed in innate immune cells which recognizes single strand RNA virus by promoting the production of antibodies against the virus and the generation of pro-inflammatory cytokines including IL-6 and IL-1 family members. Moreover, in women the production of inflammatory IL-6 after viral infection is lower than in males and is often correlated with a better longevity. In addition, on the X chromosome there are loci that code for the genes involved in the regulation of immune cells such as FOXP3, and transcription factor for Treg involved in virus pathogenesis. The X chromosome influences the immune system by acting on many other proteins, including TLR8, CD40L and CXCR3 which can be over-expressed in women, and influence the response to viral infections and vaccinations. However, the biallelic expression of the X-linked genes can promote harmful autoimmune and inflammatory responses. Cardiovascular diseases are more frequent in males and subjects without cardiovascular dysfunctions infected by CoV-19 have a better prognosis, but these effects are still under study. It is hoped that certain drugs, such as CoV-19 receptor blockers, anti-inflammatories (against rheumatic diseases), monoclonal antibodies, anti-IL-1 and anti-IL-6, the remdesevir drug (analogue adenosine, effective against ebola), hydroxychloroquine (for the treatment of malaria) and vaccines, will open up new strategies and new therapeutic ways to combat this terrible virus.
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Osteoporosis is defined as an aging-related skeletal disorder involving deterioration of bone mass and bone structure, and consequently, increased risk of fractures. Emerging evidence indicates the dysregulation of microRNAs (miRNAs) in the progression of osteoporosis. However, whether such associated miRNAs control osteoblast differentiation or constitute therapeutic targets remains elusive. In the present study, we found elevated circulating miR-374b-5p level associated with postmenopausal osteoporosis. miR-374b-5p served as a critical suppressor of osteoblast differentiation. We further identified that miR-374b-5p directly targeted Wnt family member 3 (Wnt3) and Runt-related transcription factor 2 (Runx2) through its 3'-untranslated regions (3'UTRs). Moreover, the antagonist of miR-374b-5p could promote bone formation in ovariectomy (OVX)-induced mice. Together, our results revealed that miR-374b-5p directly targeted Wnt3 and Runx2, negatively regulating osteoblast differentiation and bone formation. Collectively, circulating miR-374b-5p in the serum might serve as a potential diagnostic and therapeutic strategy for osteoporosis.
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This study aims to explore the effect of p38 mitogen-activated protein kinase and its downstream target HMG-box transcription factor 1 (HBP1) in the chondrocyte (CH) senescence caused by hyperosmotic stress. Human cartilage tissue with or without osteoarthritis (OA) were collected to detect the differential expression of p38 and HBP1 by Western blot. CHs were isolated from cartilage without OA and used the hyperosmotic medium to accelerate CH senescence in vitro. A p38 inhibitor and siRNA were used to mediate the expression of p38 and HBP1. The viability of CHs was determined by cell counting kit 8 (CCK8) assay. CH-related mRNA expression was analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Immunofluorescence was also used to detect collagen II and beta-galactosidase expression. Senescent cells were increased in both OA cartilage and hyperosmotic stress treatment with a marked upregulation of p38 and HBP1. Suppression of p38 activation reversed the hyperosmotic stress-induced CH senescence and led to an inhibition of HBP1, p16, Runx-2, MMP-13, collagen X expression, and an upregulation of collagen II and SOX-9 expression. Moreover, the silencing of HBP1 also played a protective effect on CH senescence. The suppression of the p38/HBP1 pathway alleviates the hyperosmotic stress-induced senescent progression of CHs.
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To study changes in the sonic hedgehog (Shh) signaling pathway in acute myocardial infarction (AMI) and the protective effect of changes in Shh signaling pathway activity on AMI, specific pathogen-free (SPF) C57BL/6 mice were treated with left anterior descending (LAD) ligation to establish an AMI model. The samples were collected on the 1st, 3rd, 14th, and 21st days after AMI induction. After the operations, the mice were administered the Shh signaling pathway receptor agonist SAG1.3 (5 mg/kg/d) and antagonist SANT-1 (3.3 mg/kg/d) by intraperitoneal injection. The myocardial ischemia model was established by oxygen glucose deprivation (OGD) in vitro. The AMI mouse model and the in vitro OGD-induced myocardial ischemia model were established. The Smo agonist SAG1.3 was used to activate the Shh signaling pathway, thereby reducing the expression of Bcl-2 and Bax. The number of apoptotic cells was reduced. Administration of the antagonist SANT-1 inhibited Shh signaling pathway activity by increasing the expression of Bcl-2 and Bax, and the number of apoptotic cells increased. In conclusion, activation of the Shh signaling pathway improved cardiac functions and myocardial remodeling and reduced the apoptosis of myocardial cells.
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Chondrocyte apoptosis is linked to cartilage degeneration, and considered as a crucial event during the development of osteoarthritis (OA). X inactive specific transcript (XIST) is an oncogenic long non-coding RNA (lncRNA). However, its role in the pathophysiological process of OA remains largely unknown. In this work, quantitative real-time reverse transcriptase PCR (qRT-PCR) was employed to measure the expression of XIST, miR-653-5p and sirtuin1 (SIRT1) mRNA in OA and normal cartilage tissues. Chondrocyte cell lines, CHON-001 and ATDC5, were treated with different doses of interleukin- 1β (IL-1β) to mimic the inflammatory environment of OA in vitro. Overexpression plasmids, microRNA (miRNA) mimics, miRNA inhibitors and small interfering RNAs (siRNAs) were constructed and transfected into CHON-001 and ATDC5 cells. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay was adopted to determine the cell viability. Western blot was used to detect the expression of apoptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was employed to probe the expression levels of inflammatory factors. Flow cytometry was used to analyze the cell apoptosis. StarBase and TargetScan databases were used to predict the binding sites between XIST and miR-653-5p, miR-653-5p and 3'UTR of SIRT1, respectively, which were then verified by dual luciferase reporter assay. The data in the present study demonstrated that XIST and SIRT1 were down-regulated while miR-653-5p was up-regulated in OA tissues and cell models. The up-regulation of XIST increased the viability of CHON-001 and ATDC5 cells, while it impeded their apoptosis and inflammatory response induced by IL-1β. Conversely, miR-653-5p had opposite effects. It was proved that miR-653-5p could be sponged and suppressed by XIST. Additionally, SIRT1 was identified as a target of miR-653-5p, and SIRT1 could be suppressed by XIST indirectly. In conclusion, down-regulated XIST was involved in the injury of chondrocytes during the pathophysiological process of OA, and XIST up-regulation protected chondrocytes from inflammatory injury via regulating miR-653-5p/SIRT1 axis
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Recently, important regulatory mechanisms of microRNAs (miRNAs) have been widely reported in human cancers including cervical cancer. The purpose of this study is to preliminarily clarify the function of miR-1294 in cervical cancer. The expression of miR-1294 or FLOT1 was detected using RT-qPCR or Western blot analysis. MTT, Transwell and luciferase reporter assays were used to explore the functional mechanism of miR-1294. The results showed that miR-1294 expression was decreased in cervical cancer. Functionally, overexpression of miR-1294 restrained the viability and metastasis of cervical cancer cells. MiR-1294 can also block EMT and suppress β-catenin expression in cervical cancer cells. Additionally, FLOT1 was confirmed to be a direct target of miR-1294. The knockdown of FLOT1 impeded the progression of cervical cancer. More importantly, miR-1294 inhibited the occurrence of cervical cancer by interacting with FLOT1. In conclusion, miR-1294 inhibits cell viability, migration and invasion by suppressing FLOT1 expression.
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Many lncRNAs have been reported to affect cerebral ischemia/reperfusion (I/R) injury. The purpose of this study is to elucidate the role of lncRNA NEAT1 as well as the regulatory mechanism of lncRNA NEAT1/miR-874-3p in cerebral I/R injury. A cellular model of cerebral I/R injury was built. RT-qPCR was used to detect NEAT1 and miR-874-3p expression. Cell viability was detected by MTT assay. The expression of apoptosis-related proteins (Bcl-2 and Bax) was measured by Western blot analysis. The relationship between NEAT1 and miR-874-3p was confirmed by dual luciferase reporter assay. We found that LncRNA NEAT1 was upregulated in the PC12 cells treated by I/R and upregulation of lncRNA NEAT1 can aggravate I/R injury of PC12 cells. Additionally, lncRNA NEAT1 overexpression decreased cell viability and induced apoptosis in PC12 cells treated by I/R. Furthermore, miR-874-3p was confirmed to be a target of lncRNA NEAT1. mR-874-3p and NEAT1 expression are found to be reciprocally inhibited in PC12 cells. In summary, LncRNA NEAT1 aggravates cerebral I/R injury by suppressing miR-874-3p expression.
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Long noncoding RNA (lncRNA) LINC00473 has been reported to be involved in the regulation of several human cancers. However, the regulatory mechanism of LINC00473 is still unknown in lung adenocarcinoma. In this study, RT-qPCR was used to measure the expression of LINC00473, miR-1294 and ROBO1. The functional mechanism of the LINC00473/miR-1294/ROBO1 pathway was investigated by CCK-8, Transwell and dual luciferase reporter assays. The results showed that LINC00473 was up-regulated and miR-1294 was down-regulated in lung adenocarcinoma tissues and cells. LINC00473 can bind to miR-1294, and reciprocal inhibition between LINC00473 and miR-1294 expression was identified in lung adenocarcinoma. Functionally, LINC00473 promoted cell proliferation and motility in lung adenocarcinoma by downregulating miR-1294. In addition, miR-1294 directly targets ROBO1. ROBO1 served as an oncogene in lung adenocarcinoma. In particular, LINC00473 promoted the progression of lung adenocarcinoma by upregulating ROBO1. In conclusion, LINC00473 acts as a tumor promoter in lung adenocarcinoma by regulating the miR-1294/ROBO1 axis.
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Naringenin is a flavonoid compound with antioxidant effects. It is used to treat oxidative stress-related diseases, but its mechanism is unclear. In this experiment, we explored whether naringenin can increase the expression of superoxide dismutase 1(SOD1), reduce the oxidative stress of PC12 cells induced by homocysteine (Hcy), and decrease the apoptosis of PC12 cells induced by Hcy by inhibiting the expression of mir-224-3p. Different concentrations of Hcy (1, 3, 5, 8, and 10 mmol/L) was used to analyze effect of homocysteine on PC12 cells. A total of 5 mmol/L Hcy was used to induce the excitatory and neurotoxicity model of PC12 cells in vitro. The cells were divided into normal control, Hcy induction, Hcy + Naringenin (25 μM), Hcy + Naringenin (50 μM), Hcy + Naringenin (75 μM), Hcy + Naringenin (100 μM), and Hcy + Naringenin (150 μM) groups. The relative survival rate and activities of the PC12 cells were determined by the MTT method, and the apoptosis rate of the PC12 cells was determined by using flow cytometry. The Western blot method was used to determine the expressions of SOD1, Bax, Caspase-3, Caspase-8, and Bcl-2 in the PC12 cells induced by Hcy. The expressions of SOD1 mRNA and miR-224-3p in the Hcy-induced PC12 cells were determined by RT-PCR. Results found that Hcy increased the expression of miR-224-3p in a dose-dependent manner but decreased that of SOD1 mRNA and protein. Hcy also increased oxidative stress in the PC12 cells and the proapoptotic proteins Bax, Caspase-3, and Caspase-9. Furthermore, it decreased the expression of anti-apoptotic protein Bcl-2 and the activity and survival rate of the HT22 cells, but it increased the apoptosis of the PC12 cells. The treatment of Hcy-induced PC12 cells with different concentrations of naringenin for 24 h decreased the expression of miR-224-3p in a dose-dependent manner and increased the expressions of SOD1 mRNA and protein. The treatment also decreased the oxidative stress in the PC12 cells and the expressions of pro-apoptotic proteins Bax, Caspase-3, and Caspase-9; increased the expression of anti-apoptotic protein Bcl- 2; decreased the apoptosis of the PC12 cells; and increased the PC12 cells.The results suggest that Naringenin can decrease the apoptosis and oxidative stress of PC12 cells induced by Hcy and increase the activities and survival rates of PC12 cells. The mechanism may be related to naringenin decreasing the expression of miR-224-3p in PC12 cells induced by Hcy and increasing the expressions of SOD1 mRNA and protein.
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This study explored the effects of propofol on the cognitive function and expressions of superoxide dismutase (SOD) and malondialdehyde (MDA) through the silent information regulator 1 (SIRT1) signaling pathway during cerebral ischemia-reperfusion (I/R) injury. C57BL/6J mice were used and divided into Sham group, I/R group (I/R model established via ligation of artery) and Treated group (peritoneal injection of propofol) according to different treatments. The memory ability of mice was evaluated using Morris water maze test, and the motor coordination was assessed using Rota rod test and oblique beam walking test. The brain tissues were prepared into embedded sections, and then the pathological changes in brain neurons were detected via hematoxylin-eosin (HE) staining, and the changes in apoptosis of brain tissues were detected via flow cytometry. Moreover, after the mice were anesthetized and sacrificed, the brain tissues were isolated and whole blood was collected. Then the changes in SIRT1 protein were determined using Western blotting, and the changes in MDA and SOD activity were determined through biochemical assays. The results of Morris water maze test and elevated plus-maze test revealed that transfer latency time (TLT) was significantly prolonged, and escape latency time (ELT) was significantly shortened in the I/R group compared with those in Sham group (*P<0.05), indicating memory impairment after cerebral I/R injury. TLT was shortened, and ELT was significantly prolonged in the Treated group compared with those in I/R group (#P<0.05). In Rota rod test, the falling down time was obviously shorter in the I/R group than in the Sham group (*P<0.05), while it was obviously longer in the Treated group than that in the I/R group (#P<0.05). Compared with the Sham group, the I/R group had neurological impairment, manifested as the evident increase in motor performance score (*P<0.05), and the motor performance score in the Treated group was evidently lower than that in the I/R group (#P<0.05). The apoptosis was markedly enhanced in the I/R group (*P<0.05), while it was markedly weakened in the Treated group (#P<0.05) compared with that in the Sham group. In addition, the results of Western blotting showed that the expression of SIRT1 was evidently higher in I the /R group than that in the Sham group, while it evidently declined after treatment with propofol (P<0.05).
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The senescence and degeneration of the intervertebral disc are closely related to the reduction of nucleus pulposus (NP) cells caused by apoptosis. TIR-domain-containing adapter-inducing interferon-β (TRIF) is an adapter for Toll-like receptors 3/4 (TLR3/4), which involves in cell apoptosis. The aim of this study is to detect the role of TRIF in the apoptotic progress of NP cells. The expression of collagen II, aggrecan, TLR3/4, and TRIF were analyzed in different degrees of degenerated human NP samples from patients. NP cells were isolated from mild degenerated tissues and cultured with IL-1β to accelerate the degradation, and treated with TLR3/4 protein. siRNA was used to silence TRIF gene expression, and TRLF-plasmid was used to upregulate TRLF gene expression. We used flow cytometry assay to analyze cell apoptosis. The expression of collagen II, aggrecan, TLF3/4, TRIF, caspase-8/3, MMP-13, TNF-α was determined by immunofluorescence, Western blot, or RT-PCR. That the expression of collagen II and aggrecan markedly decreased, but TLF3/4, TRIF, caspase-8/3, MMP-3, TNF-α, and IL-1β were increased in severely degenerated disc tissues. IL-1β treatment induced NP cell degeneration and TLF3/4, TRIF, caspase-8/3, MMP-3, TNF-α overexpression. TLF3/4 protein treatment promoted NP cell degeneration and apoptosis by upregulation of TRIF, caspase-8/3, MMP-3, and TNF-α. Furthermore, TRIF silencing reversed the negative effect of TLF3/4 overexpression, and TRIF overexpression played the same role in NP cell apoptosis. Based on these results, we believe that TRIF is activated in a degenerated intervertebral disc. TLF3/4 promotes NP cell apoptosis and inflammation through the TRLF adaptor. TRLF expression is positively related to the apoptosis and inflammation in NP cells. These results suggest a therapeutic potential of the TRIF in the treatment of disc degeneration.
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The aim of this study was to explore the effects of Caveolin-1 on lung injury in rats with chronic obstructive pulmonary disease (COPD). The forced expiratory volume in 0.3 s/forced vital capacity (FEV0.3/ FVC) and peak expiratory flow (PEF) were determined. The total white blood cells (WBC), neutrophil ratio (NEUT%), mononuclear macrophage ratio (MNM%), lymphocyte ratio (LY%) and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Both FEV0.3/FVC and PEF significantly declined in the COPD group compared with those in the Control group, while they significantly rose in the IWR-1 group and Daidzin group compared with those in the COPD group. HE staining showed that there were alveolar dilatation and enlargement with obviously increased intercept in the COPD group, while there were basically no changes in the alveoli in the IWR-1 group and Daidzin group. Massive apoptosis of alveolar tissues was observed in COPD group, and there was only a little apoptosis in IWR-1 group and Daidzin group. In COPD group, WBC, NEUT% and protein concentration in BALF were obviously increased, MNM% was obviously decreased, and there was no obvious difference in LY% compared with those in the Control group. In the the IWR-1 group and Daidzin group, WBC, NEUT%, protein concentration, MNM% and LY% in BALF had no obvious differences compared with those in the Control group. In the IWR-1 group and Daidzin group, WBC, NEUT% and protein concentration evidently declined, MNM% evidently rose, and there was no obvious difference in LY% compared with those in the COPD group. Caveolin-1, Wnt-1 and β-catenin in lung tissues were remarkably higher in the COPD group than those in the Control group. Caveolin-1 was remarkably higher in the IWR-1 group than that in the Control group. And Wnt-1 and β-catenin were higher in the Daidzin group than those in the Control group. In addition, Wnt-1 and β-catenin in lung tissues markedly declined in the IWR-1 group compared with those in the COPD group. Caveolin-1, Wnt-1 and β-catenin in lung tissues also markedly declined in the Daidzin group compared with those in the COPD group. Caveolin-1 can improve lung injury in COPD rats through the Wnt/β-catenin signaling pathway.
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Ovarian cancer (OC) is one of the most common gynecological malignancies, with the highest mortality rate in women worldwide. LINC00662, a long non-coding RNA (lncRNA), was shown to play a vital role in many malignancies, while little is known about its role in OC. Firstly, our study determined the expression of LINC00662 in OC tissues and cells. Upregulation or downregulation of LINC00662 were performed in OC cells to explore its effects on cell proliferation and glycolysis of OC. The interaction between LINC00662 and miR-375 was verified using luciferase assays and RNA immunoprecipitation. Results showed that LINC00662 was highly expressed in OC tissues and cells, and patients with increased expression of LINC00662 were associated with shorter overall survival. Furthermore, functional assays proved that LINC00662 was essential for OC cell proliferation and glycolysis. Subsequently, our study further revealed that LINC00662 acted as a competitive RNA and it could modulate the expression of HIF-1α through directly binding with miR-375. Collectively, upregulation of LINC00662 in ovarian cancer tissues is closely correlated to poor survival. LINC00662 might regulate HIF-1α expression via miR-375. These findings suggested that LINC00662 has the potential to be explored as a diagnostic biomarker for OC.
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Nasopharyngeal carcinoma (NPC) is a main type of otolaryngological malignancy. In many cancers, miR-206 functions as a tumor suppressor, suppressing cell proliferation, migration and invasion. The purpose of this study was to explore how miR-206 worked on cell metastasis in NPC. The mRNA levels of miR-206 and G6PD were determined in NPC tissues and cell lines by RT-qPCR and Western blot. Transwell assay was applied to evaluate the migratory and invasive capacities. Dual luciferase reporter assay was employed to confirm that miR-206 mediated the expression of G6PD in C666-1 cells. In this study, miR- 206 was downregulated, whereas G6PD was upregulated in NPC tissues and cell lines. In addition, G6PD was identified as a direct target gene of miR-206 in C666-1 cells. The expression of G6PD was mediated by miR-206, which could partially reverse the inhibitory effects of miR-206 on the migration, invasion and EMT in C666-1 cells. In conclusion, miR-206 regulated the migratory, invasive and EMT abilities through directly targeting the 3'-UTR of G6PD mRNA in C666-1 cells. The newly identified miR-206/G6PD axis provides novel insight into the pathogenesis of nasopharyngeal carcinoma.
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MiR-20a shows a significant role in the development of various human tumors. However, its specific biological function in non-small-cell lung cancer (NSCLC) is still not clear. qRT-PCR was applied for detecting miR-20a expression. The analysis of cell growth and apoptosis were performed by MTT, xenograft models, Western blot assays. Dual luciferase reporter, Western blotting and qRT-PCR were carried out to verify the potential target of miR-20a. In NSCLC tissues and cells, miR-20a was highly expressed and RUNX3 was lowly expressed. Moreover, up-regulation of miR-20a expression promoted NSCLC cell proliferation, invasion and migration, while low-expression of miR-20a showed the converse case on cell proliferation, invasion and migration. RUNX3 was verified as the direct target of miR-20a and it could overturn its biological function in NSCLC cells. Moreover, miR-20a negatively regulated RUNX3 expression. Mechanistically, increasing miR-20a expression inhibited RUNX3 expression and then activated the TGF-β signaling pathway. Taken together, our results demonstrated that re-expression of miR-20a promoted lung tumorigenesis by down-regulation of RUNX3 and facilitating the activation of TGF-β signaling pathway.
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The aim of this study was to investigate whether LINC01305 can regulate TNXB-mediated phosphatidilinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and therefore affect epithelial mesenchymal transition in lung cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect LINC01305 level in 52 non-small cell lung cancer (NSCLC) tissues and paracancerous normal lung tissues, and the relationship between LINC01305 expression and clinical pathological parameters of these subjects was analyzed. After LINC01305 was knocked down in PC9 cell and overexpressed in A549 cells, qRT-PCR was used to verify the transfection efficiency, and nuclear fractionation technique, cell counting kit-8 (CCK-8), plate cloning assay and Transwell test were used to detect the effect of LINC01305 on cell viability. LINC01305 had an obviously higher expression in NSCLC tissues, and the expression in lung cancer patients with tumor size >3 cm was higher than those with tumor ≤3 cm. LINC01305 expression in tumor tissues in T3-T4 stage was obviously higher than those in T1-T2 stage, and the overall survival rate of lung cancer patients with high expression of LINC01305 was lower than those with low expression. Moreover, clinical analysis revealed that LINC01305 level was related to tumor size, TNM stage and lymph node metastasis of patients with lung cancer, but not related to age or gender. Silencing LINC01305 can inhibit the epithelial mesenchymal transition-induced transformation of lung cancer cells through regulating TNXB-mediated PI3K/Akt signaling pathway, which in turn affects the progression of lung cancer
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The aim of this study is to explore the regulatory effect of micro ribonucleic acid (miR)-19a on diabetic retinopathy (DR) through mediating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/protein kinase B (Akt) signaling pathway. Thirty male Sprague-Dawley rats were first divided into Healthy group, DR group and miR-19a inhibitor group. The DR model was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). The retinal tissues were dissected and RGCs were isolated. The expression level of miR-19a therein was determined using quantitative polymerase chain reaction (qPCR). The pathological changes were observed through hematoxylin-eosin staining (HE) staining. The apoptosis was detected by flow cytometry. PTEN was predicted as a target gene of miR-19a through TargetScan biological software. The protein expression of PTEN was detected via immunofluorescence assay. The changes in the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt pathway-associated proteins were detected using Western blotting. The expression of miR-19a declined substantially in DR rats injected with miR-19a inhibitor (P<0.05). RGCs were arranged regularly, showing apoptosis and milder necrosis in miR-19a inhibitor group. The proportion of apoptotic cells was substantially decreased in miR-19a inhibitor group (P<0.05). It was found that miR-19a inhibitor group exhibited an evidently lower protein expression of PTEN and a higher activation degree of the Akt pathway than DR group (P<0.05). MiR-19a binds to PTEN protein in a targeted manner to mediate the PI3K/Akt pathway, thereby affecting the progression of DR.
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Small nucleolar RNA host genes (SNHGs) as a subset of long noncoding RNAs (lncRNAs) have critical roles in the pathogenesis of multiple malignancies, however, the role and molecular mechanisms of lncRNA SNHG8 in osteosarcoma (OS) remain unclear. In the present study, the correlation of SNHG8 or miR-542-3p with clinicopathological elements and prognosis in OS patents was estimated by TCGA cohort. Cell viability and invasion were assessed by MTT and Transwell assays. The interplay between SNHG8 and miR-542-3p was affirmed by a luciferase report assay. The effects of SNHG8 on miR-542-3p expression were examined in MG-63 and SW-1353 cells by qRT-PCR analysis. The results showed that incremental expression of SNHG8 or reduced expression of miR-542-3p was related to poor survival and tumor recurrence in OS patients. Overexpressing SNHG8 accelerated the growth and invasion of MG-63 cells, but silencing SNHG8 harbored an opposite effect in SW-1353 cells. Additionally, SNHG8 could negatively regulate miR-542-3p expression and bind with miR-542-3p, which attenuated SNHG8 induced cell proliferation. Taken together, these findings indicate that lncRNA SNHG8 promotes the proliferation of OS cells by downregulating miR-542-3p.
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To explore effects of the sDR5-Fc fusion protein on ulcerative colitis of infant mice via the TRAIL-DR5 pathway, 50 female mice were randomly divided into 5 groups, i.e., control group (group A), dextran sulfate sodium group (group B), hIgG group (group C), 10 mg/kg sDR5-Fc group (group D), and 20 mg/ kg sDR5-Fc group (group E). The acute ulcerative colitis models were established. The weights and disease activity index (DAI) of each group were monitored daily. In addition, the pathological changes of colon tissues were observed by Hematoxylin-Eosin staining. The number of macrophages in colon tissues was detected by immunohistochemistry assay. Changes in the expression of inflammatory factors in colon tissues were detected by quantitative real-time polymerase chain reaction (PCR). Lipopolysaccharide (LPS) of different concentrations was utilized alone or in combination with TRAIL to stimulate the NCM460 cells. The activation of NLRP3 inflammasomes was detected by Western blot. The apoptosis of NCM460 cells was detected by flow cytometry. The results showed that in groups B and C, the body weights decreased, the DAI increased, the colon epithelial cells were injured, the inflammatory cells were infiltrated, and the macrophages in colon tissues increased significantly. In groups D and E, the body weights increased, the DAI decreased, the inflammation was significantly improved, the macrophages decreased significantly, and the gene expression levels of NLRP3, Caspase-1, and IL-1β decreased significantly. Thus, sDR5-Fc could inhibit the activation of NLRP3 inflammasomes induced by TRAIL, thereby decreasing the apoptosis of NCM460 cells. In conclusion, the sDR5-Fc fusion protein could block the TRAIL-DR5 pathway to reduce the expression of NLRP3 inflammasomes, thereby improving ulcerative colitis.
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Parkinson's disease (PD), which is not only a motor disease, is one of the most frequent neurodegenerative diseases and affects 1.5-2% of people worldwide. The role of its non motor-symptoms is of first importance on quality of life. Speech impairment is considered a part of motor impairment and is widespread in PD where most frequent speech impairment is Hypokinetic dysarthria, a disorder characterized by reduced articulation movements and phonetic monotony. Many PD patients show difficulty in accessing the lexicon related to cognitive impairment. Clinical evaluation of speech disorders in PD includes the clinical history, verbal and non-verbal assessment of the voice, evaluation of the calibre of the language. It is also important to self-assess speech disturbances because PD patients often do not realize their own deficits. Self-assessment tests comprise subjective assessment of communicative disorder in different social situations, description of adopted strategies, perception of the reactions of interlocutors. The comparison between perceptive and subjective examination of speech disorders in PD patients are described in order to evaluate the presence of these deficits and their impact on quality of life in order to initiate early treatment with specific speech therapy.
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