LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis.

BACKGROUND: Ferroptosis is involved in osteoarthritis development; however, the roles of long noncoding RNAs (lncRNAs), including lncRNA MEG3, in the regulation of ferroptosis in osteoarthritis are still unclear. METHODS: In this study, qRT‒PCR and Western blotting assays were used to detect the expression of lncRNA MEG3, miR-885-5p, SLC7A11 and GPX4; MDA and CCK-8 assays were applied to analyse cellular MDA levels and cell viability, respectively. RESULT: Erastin elevated cellular MDA levels and decreased the viability of chondrocytes and the erastin-induced decline in cell viability was reversed by a ferroptosis inhibitor (ferrostatin-1). Erastin downregulated lncRNA MEG3, SLC7A11 and GPX4 and upregulated miR-885-5p. Silencing of lncRNA MEG3 increased miR-885-5p and downregulated SLC7A11 and GPX4 and further sensitized chondrocytes to erastin-induced ferroptosis. In contrast, overexpression of lncRNA MEG3 had opposite effects. Dual luciferase assays confirmed binding between lncRNA MEG3 and miR-885-5p and between miR-885-5p and the 3'UTR of SLC7A11. In the synovial fluids from patients with osteoarthritis compared with synovial fluids from normal controls, the RNA levels of lncRNA MEG3 and SLC7A11 were decreased and the miR-885-5p expression level was increased. CONCLUSION: Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.

Association of SGLT2is with cardiovascular and reproductive diseases: a meta-analysis based on 14 large-scale randomized trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can improve long-term cardio-renal outcomes in patients with diabetes, heart failure (HF), or renal failure. We aimed to investigate the association of SGLT2is with the risks of various cardiovascular and reproductive diseases. METHODS: Large-scale randomized trials enrolling more than 1000 participants and assessing SGLT2is were included. Outcomes of interest were the various serious adverse events related to cardiovascular or reproductive diseases. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 14 large trials and evaluated 169 types of cardiovascular and reproductive diseases. SGLT2is were significantly associated with the lower risks of 13 types of cardiovascular diseases, e.g., cardiac failure chronic (RR 0.70, 95% CI 0.57-0.87), cardiac failure congestive (RR 0.74, 95% CI 0.66-0.83), acute cardiac failure (RR 0.72, 95% CI 0.60-0.86), coronary artery disease (RR 0.75, 95% CI 0.58-0.97), ischemic cardiomyopathy (RR 0.72, 95% CI 0.52-0.99), atrial fibrillation (RR 0.88, 95% CI 0.78-0.99), bradycardia (RR 0.72, 95% CI 0.53-0.99), and hypertension (RR 0.70, 95% CI 0.54-0.91). SGLT2is were not significantly associated with 18 types of reproductive diseases, e.g., adenomyosis, endometrial hyperplasia, and metrorrhagia. Although SGLT2is were observed to have a significant association with a higher risk of uterine prolapse, the 95% CI of RR for this outcome was relatively wide. CONCLUSION: This meta-analysis confirms the benefits of SGLT2is against chronic congestive HF again; reveals the possible benefits of SGLT2is against acute HF, myocardial infarction, arrhythmias, and hypertension; and identifies that SGLT2is are safe in general for the reproductive system.

Estrodiol-17ß and aromatase inhibitor treatment induced alternations of genome-wide DNA methylation pattern in Takifugu rubripes gonads.

Estradiol-17ß (E2) and aromatase inhibitor (AI) exposure can change the phenotypic sex of fish gonads. To investigated whether alterations in DNA methylation is involved in this process, the level of genome-wide DNA methylation in Takifugu rubripes gonads was quantitatively analyzed during the E2-induced feminization and AI-induced masculinization processes in this study. The methylation levels of the total cytosine (C) in control-XX(C-XX), control-XY (C-XY), E2-treated-XY (E-XY) and AI-treated-XX (AI-XX) were 9.11%, 9.19%, 8.63% and 9.23%, respectively. In the C-XX vs C-XY comparison, 4,196 differentially methylated regions (DMRs) overlapped with the gene body of 2,497 genes and 608 DMRs overlapped with the promoter of 575 genes. In the E-XY vs C-XY comparison, 6,539 DMRs overlapped with the gene body of 3,416 genes and 856 DMRs overlapped with the promoter of 776 genes. In the AI-XX vs C-XX comparison, 2,843 DMRs overlapped with the gene body of 1,831 genes and 461 DMRs overlapped with the promoter of 421 genes. Gonadal genomic methylation mainly occurred at CG sites and the genes that overlapped with DMRs on CG context were most enriched in the signaling pathways related to gonad differentiation, such as the Wnt, TGF-ß, MAPK, CAM and GnRH pathways. The DNA methylation levels of steroid synthesis genes and estrogen receptor genes promoter or gene body were negative correlated with their expression. After bisulfite sequencing verification, the DNA methylation level of the amhr2 promoter in XY was increased after E2 treatment, which consistent with the data from the genome-wide DNA methylation sequencing. In C-XY group, the expression of amhr2 was significantly higher than that in E-XY (p < 0.05). Additionally, dnmt1, which is responsible for methylation maintenance, expressed at similar level in four groups (p > 0.05). dnmt3, tet2, and setd1b, which were responsible for methylation modification, expressed at significantly higher levels in E-XY compared to the C-XY (p < 0.05). Dnmt3 and tet2 were expressed at significantly higher levels in AI-XX than that in C-XX (p < 0.05). These results indicated that E2 and AI treatment lead to the aberrant genome-wide DNA methylation level and expression level of dnmt3, tet2, and setd1b in T. rubripes gonad.

Alterations of brain gray matter volume in children with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA. Method: Eighty-three children aged 8-13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA). Results: The gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus. Conclusion: Our results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.

Retinal development and the expression profiles of opsin genes during larval development in Takifugu rubripes.

The light-sensitive capacity of fish larvae is determined by the structure of the retina and the opsins expressed in the retinal and nonretinal photoreceptors. In this study, the retinal structure and expression of opsin genes during the early developmental stage of Takifugu rubripes larvae were investigated. Histological examination showed that at 1 days after hatching (dah), seven layers were observed in the retina of T. rubripes larva, including the pigment epithelial layer [retinal pigment epithelium layer (RPE)], photoreceptor layer (PRos/is), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL) and ganglion cell layer (GCL). At 2 dah, optic fibre layer (OFL) can be observed, and all eight layers were visible in the retina. By measuring the thickness of each layer, opposing developmental trends were found in the thickness of ONL, OPL, INL, IPL, GCL and OFL. The nuclear density of ONL, INL and GCL and the ratios of ONL/INL, ONL/GCL and INL/GCL were also measured and the ratio of ONL/GCL ranged from 1.9 at 2 dah to 3.4 at 8 dah and no significant difference was observed between the different developmental stages (P > 0.05). No significant difference was observed for the INL/GCL ratio between the different developmental stages, which ranged from 1.2 at 2 dah to 2.0 at 18 dah (P > 0.05). The results of quantitative real-time polymerase chain reaction (PCR) showed that the expression of RH1, LWS, RH2-1, RH2-2, SWS2, rod opsin, opsin3 and opsin5 could be detected from 1 dah. These results suggest that the well-developed retina and early expression of the opsins of T. rubripes during the period of transition from endogenous to mixed feeding might be critical for vision-based survival skills during the early life stages after hatching.

HTCA: a database with an in-depth characterization of the single-cell human transcriptome.

Single-cell RNA-sequencing (scRNA-seq) is one of the most used single-cell omics in recent decades. The exponential growth of single-cell data has immense potential for large-scale integration and in-depth explorations that are more representative of the study population. Efforts have been made to consolidate published data, yet extensive characterization is still lacking. Many focused on raw-data database constructions while others concentrate mainly on gene expression queries. Hereby, we present HTCA (www.htcatlas.org), an interactive database constructed based on ∼2.3 million high-quality cells from ∼3000 scRNA-seq samples and comprised in-depth phenotype profiles of 19 healthy adult and matching fetal tissues. HTCA provides a one-stop interactive query to gene signatures, transcription factor (TF) activities, TF motifs, receptor-ligand interactions, enriched gene ontology (GO) terms, etc. across cell types in adult and fetal tissues. At the same time, HTCA encompasses single-cell splicing variant profiles of 16 adult and fetal tissues, spatial transcriptomics profiles of 11 adult and fetal tissues, and single-cell ATAC-sequencing (scATAC-seq) profiles of 27 adult and fetal tissues. Besides, HTCA provides online analysis tools to perform major steps in a typical scRNA-seq analysis. Altogether, HTCA allows real-time explorations of multi-omics adult and fetal phenotypic profiles and provides tools for a flexible scRNA-seq analysis.

LncXIST Facilitates Iron Overload and Iron Overload-Induced Islet Beta Cell Injury in Type 2 Diabetes through miR-130a-3p/ALK2 Axis.

Iron overload is directly associated with diabetes mellitus, loss of islet beta cell, and insulin resistance. Likewise, long noncoding RNA (lncRNA) is associated with type 2 diabetes (T2D). Moreover, lncRNAs could be induced by iron overload. Therefore, we are going to explore the molecular mechanism of lncRNA XIST in iron overload-related T2D. Real-time quantitative PCR and Western blot were used to detect gene and protein levels, respectively. TUNEL and MTT assay were performed to examine cell survival. The glucose test strip, colorimetric analysis kit, ferritin ELISA kit, and insulin ELISA kit were performed to examine the levels of glycolic, iron, and total iron-binding capacity, ferritin, and insulin in serum. Fluorospectrophotometry assay was used to examine labile iron pool level. XIST was higher expressed in T2D and iron overload-related T2D rat tissues and cells, and iron overload-induced promoted XIST expression in T2D. Higher XIST expression was associated with iron overload in patients with T2D. Knockdown of XIST alleviated iron overload and iron overload-induced INS-1 cells injury. Further, we found that XIST can sponge miR-130a-3p to trigger receptor-like kinase 2 (ALK2) expression. Moreover, knockdown of ALK2 alleviated iron overload and iron overload-induced INS-1 cells injury by inhibiting bone morphogenetic protein 6 (BMP6)/ALK2/SMAD1/5/8 axis but reversed with XIST upregulation, which was terminally boosted by overexpression of miR-130a-3p. XIST has the capacity to promote iron overload and iron overload-related T2D initiation and development through inhibition of ALK2 expression by sponging miR-130a-3p, and that targeting this axis may be an effective strategy for treating patients with T2D.

miR-433-3p Targets AJUBA to Inhibit Malignant Progression of Glioma.

INTRODUCTION: Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers. METHODS: In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis. RESULTS: In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression. CONCLUSION: These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.

Screening of CXC chemokines in the microenvironment of ovarian cancer and the biological function of CXCL10.

BACKGROUND: This study aims to screen and identify the biological functions and prognostic value of CXC chemokines in ovarian cancer (OC) through bioinformatics and molecular biology methods, and to provide data support for the selection of biomarkers and prognostic analysis of OC. METHODS: In this study, GEO, ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, STRING, TRRUST, and TIMER databases were used to study CXC chemokines. Angiogenesis and T cell killing assay were used to detect the effect of CXCL10 on tumor cell immunity and angiogenesis. Real-time quantitative PCR (qRT-PCR), immunoblotting, and ectopic tumor formation experiments were used to verify the effect of CXCL10 on ovarian cancer tumors. RESULTS: We found that CXCL1, CXCL10, CXCL11, CXCL13, and CXCL14 were significantly upregulated in OC samples compared with normal tissues. Our data showed that there was a relationship between the expression of CXC chemokines and the infiltration of six types of immune cells significant correlation. In vitro assay confirmed that overexpression of CXCL10 could enhance the killing effect of T cells and inhibit angiogenesis. Further in vivo assay had shown that CXCL10 could affect the progression of ovarian cancer by increasing the expression of cytotoxic T cells and inhibiting angiogenesis. CONCLUSION: In conclusion, we hope that our data will provide new insights into the development of immunotherapy and the selection of prognostic markers for patients with OC.

Profile of gene expression changes during estrodiol-17ß-induced feminization in the Takifugu rubripes brain.

BACKGROUND: As the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17ß (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish. RESULTS: In this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshß, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism. CONCLUSION: A number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.

Magnetic nanoparticles for cancer theranostics: Advances and prospects.

Cancer is one of the leading causes of mortality worldwide. Nanoparticles have been broadly studied and emerged as a novel approach in diagnosis and treatment of tumors. Over the last decade, researches have significantly improved magnetic nanoparticle (MNP)'s theranostic potential as nanomedicine for cancer. Newer MNPs have various advantages such as wider operating temperatures, smaller sizes, lower toxicity, simpler preparations and lower production costs. With a series of unique and superior physical and chemical properties, MNPs have great potential in medical applications. In particular, using MNPs as probes for medical imaging and carriers for targeted drug delivery systems. While MNPs are expected to be the future of cancer diagnosis and precision drug delivery, more research is still required to minimize their toxicity and improve their efficacy. An ideal MNP for clinical applications should be precisely engineered to be stable to act as tracers or deliver drugs to the targeted sites, release drug components only at the targeted sites and have minimal health risks. Our review aims to consolidate the recent improvements in MNPs for clinical applications as well as discuss the future research prospects and potential of MNPs in cancer theranostics.

Genetic variants in the regulation region of TLR4 reduce the gastric cancer susceptibility.

Gastric cancer (GC) is one of the most common cancers diagnosed in China. It has been suggested that the genetic polymorphisms of Toll-like receptors (TLRs) might be in close relation to tumorigenesis and development of gastric cancer. In this study, we performed a case-control study to investigate the genetic polymorphisms of TLR3, 4, 5, 7 with the genetic susceptibility of gastric cancer. TLRs gene polymorphisms in 471 gastric cancer (GC) patients and 471 healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis or TaqMan assays. Odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the association of TLR4 variants with the GC risk via unconditional logistic regression. Our results suggested that variant genotypes of TLR4 rs7869402 (OR = 0.61, 95%CI = 0.40-0.92, P = 0.02) and TLR4 rs7873784 (OR = 0.17, 95%CI = 0.09-0.33, P < 0.01) gene polymorphisms reduced the risk of GC. Stratified analysis showed that rs7869402 T-containing genotype significantly decreased the susceptibility of GC among females (OR = 0.38, 95%CI = 0.16-0.91, P = 0.03), older subjects (OR = 0.48, 95%CI = 0.26-0.87, P = 0.02), non-smokers (OR = 0.41, 95%CI = 0.23-0.71, P < 0.01) and non-drinkers (OR = 0.58, 95%CI = 0.30-0.78, P < 0.01). In case of rs7873784 polymorphism, C-containing genotype reduced the risk of GC among males (OR = 0.08, 95%CI = 0.03-0.21, P < 0.01), but not among females (OR = 0.53, 95%CI = 0.22-1.27, P = 0.15). As to the other four SNPs (TLR3 rs5743303, TLR4 rs1927914, TLR5 rs1640816 and TLR7 rs3853839), no significant correlations were found to be related to the risk of gastric carcinoma. Our research demonstrated the significance of TLRs polymorphisms in decreasing the risk of GC.

LncRNA LEF1-AS1 promotes metastasis of prostatic carcinoma via the Wnt/ß-catenin pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown. METHODS: Next-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1. RESULTS: The next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44. CONCLUSION: In summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/ß-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy.

Long non­coding RNA PLK1S1 was associated with renal cell carcinoma progression by interacting with microRNA­653 and altering C­X­C chemokine receptor 5 expression.

Renal cell carcinoma (RCC) is the most common type of renal cancer. Long non­coding RNA (lncRNA) has been reported to play a vital role in the development and progression of various types of cancer type. However, the underlying molecular mechanisms of PLK1S1 in regulating RCC progression remain unclear. In the present study, PLK1S1 was upregulated in RCC tissues and cells, and PLK1S1 expression was also significantly elevated in stage IV RCC tissues. Kaplan­Meier analysis showed that patients with high PLK1S1 expression had a shorter overall survival time compared with those with low PLK1S1 expression. Moreover, bioinformatics analysis and luciferase reporter assay demonstrated that PLK1S1 inhibited microRNA (miR)­653 expression by direct interaction. Functional analyses demonstrated that a miR­653 inhibitor promoted short hairpin PLK1S1­attenuated cell proliferation, invasion and sorafenib resistance of RCC cells. In addition, C­X­C motif chemokine receptors 5 (CXCR5) was identified as an effector of PLK1S1/miR­653­mediated tumorigenesis and drug resistance in RCC cells. Lastly, xenograft experiments demonstrated that PLK1S1 knockdown inhibited tumor growth in vivo. Reverse transcription­quantitative PCR and western blot analysis revealed that PLK1S1 knockdown upregulated the expression level of miR­653, whilst downregulating the expression level of CXCR5. In conclusion, the present study revealed that PLK1S1 promoted tumor progression and sorafenib resistance in RCC through regulation of the miR­653/CXCR5 axis, which may offer a novel treatment strategy for patients with RCC.

High levels of MESP1 expression in non-small cell lung cancer can facilitate cell proliferation, metastasis and suppresses cell apoptosis.

BACKGROUND: There are growing number of researches have shown that mesoderm posterior basic helix-loop helix (BHLH) transcription factor 1 (MESP1) plays a crucial role in the development of tumors. However, its expression pattern and function in non-small cell lung cancer (NSCLC) are still unknown. METHODS: MESP1 expression and biological process were investigated in NSCLC based on bioinformatics analysis. The mRNA or protein expression levels of MESP1 were measured by quantitative real-time PCR (qRT-PCR) and western blot (WB) assay in NSCLC cells and clinical tissue samples. Then, we used small interfering RNA (siRNA) interference to knocking down expression of gene in NSCLC cells. Cell proliferation was performed using cell counting kit-8 (CCK-8), colony forming assay and real-time cell analyzer (RTCA); transwell chambers and RTCA were used to analysis cell migration and invasion. Besides, analyses of the cell cycle progression and apoptosis were measured via BD JAZZ flow cytometric analysis. All the experiments were repeated ≥3 times. And analyses were performed using SPSS software version 21.0 and GraphPad Prism 6.0. P<0.05 was considered statistically significant. RESULTS: Detection of MESP1 showed that mRNA was up-regulated in NSCLC cells and patients compared with the normal controls (P<0.05). And high expression of MESP1 were correlated with increasingly cell proliferation, metastasis, cycle and apoptosis. Besides, through WB experiments, it was found that knocking down MESP1 mainly activated the caspase-3/PARP1 signal pathway. Furthermore, it was also verified from clinical samples that MESP1 was highly expressed on both mRNA and protein aspect. CONCLUSIONS: Our study suggested that MESP1 is indeed highly expressed in NSCLC, and MESP1 high expression obviously promote cell proliferation, migration, invasion. What's more, it has good sensitivity to the occurrence and development of NSCLC patients. This can be used as a novel potential therapeutic target for NSCLC.

DDAH2 alleviates myocardial fibrosis in diabetic cardiomyopathy through activation of the DDAH/ADMA/NOS/NO pathway in rats.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension­independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl­L­arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes­related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L­NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end­diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

A Maitake (Grifola frondosa) polysaccharide ameliorates Alzheimer's disease-like pathology and cognitive impairments by enhancing microglial amyloid-ß clearance.

Alzheimer's disease (AD) is characterized by the deposition of amyloid-ß (Aß) plaques, neuronal loss and neurofibrillary tangles. In addition, neuroinflammatory processes are thought to contribute to AD pathophysiology. Maitake (Grifola frondosa), an edible/medicinal mushroom, exhibits high nutritional value and contains a great amount of health-beneficial, bioactive compounds. It has been reported that proteo-ß-glucan, a polysaccharide derived from Maitake (PGM), possesses strong immunomodulatory activities. However, whether PGM is responsible for the immunomodulatory and neuroprotection effects on APPswe/PS1ΔE9 (APP/PS1) transgenic mice, a widely used animal model of AD, remains unclear. In the present study, the results demonstrated that PGM could improve learning and memory impairment, attenuate neuron loss and histopathological abnormalities in APP/PS1 mice. In addition, PGM treatment could activate microglia and astrocytes and promote microglial recruitment to the Aß plaques. Also, PGM could enhance Aß phagocytosis, and thereby alleviate Aß burden and the pathological changes in the cortex and hippocampus in APP/PS1 mice. Moreover, PGM showed no significant effect on mice body weight. In conclusion, these findings indicated that administration of PGM could improve memory impairment via immunomodulatory action, and dietary supplementation with PGM may provide potential benefits on brain aging related memory dysfunction.

Cost-effective 33-Gbps intensity modulation direct detection multi-band OFDM LR-PON system employing a 10-GHz-based transceiver.

We develop a dynamic multi-band OFDM subcarrier allocation scheme to fully utilize the available bandwidth under the restriction of dispersion- and chirp-related power fading. The experimental results successfully demonstrate an intensity-modulation-direct-detection 34.78-Gbps OFDM signal transmissions over 100-km long-reach (LR) passive-optical networks (PONs) based on a cost-effective 10-GHz EAM and a 10-GHz PIN. Considering 0-100-km transmission bandwidth of a 10-GHz EAM, the narrowest bandwidth is theoretically evaluated to occur at ~40 km, instead of 100 km. Consequently, the performances of 20-100-km PONs are experimentally investigated, and at least 33-Gbps capacity is achieved to support LR-PONs of all possible 20-100-km radii.

21 Gb/s after 100 km OFDM long-reach PON transmission using a cost-effective electro-absorption modulator.

We experimentally demonstrate a superior performance of 2.1-Tb/s·km OFDM signal transmission over 100-km long-reach PONs. While the bandwidth of a 100-km SMF transmission system is limited to 4.3 GHz due to positive chirp, we successfully achieve spectrally-efficient 21-Gb/s signaling by using a cost-effective and low-chirp EAM, and adopting the 128-QAM format and adaptive subcarrier pre-emphasis.