Losartan alleviates renal fibrosis by inhibiting the biomechanical stress-induced epithelial-mesenchymal transition of renal epithelial cells.

Angiotensin receptor blockers (ARBs) have been reported to be beneficial of renal fibrosis, but the molecular and cellular mechanisms are still unclear. In this study, we investigated the effectiveness and relevant mechanism of ARBs in alleviating renal fibrosis, especially by focusing on biomechanical stress-induced epithelial to mesenchymal transition (EMT) of renal epithelial cells. Unilateral ureteral obstruction (UUO) renal fibrosis model was established in mice by ligating the left ureter, and then randomly received losartan at a low dose (1 mg/kg) or a regular dose (3 mg/kg) for 2 weeks. Compared to the control, histological analysis showed that losartan treatment at either a low dose or a regular dose effectively attenuated renal fibrosis in the UUO model. To further understand the mechanism, we ex vivo loaded primary human renal epithelial cells to 50 mmHg hydrostatic pressure. Western blot and immunostaining analyses indicated that the loading to 50 mmHg hydrostatic pressure for 24 h significantly upregulated vimentin, ß-catenin and α-SMA, but downregulated E-cadherin in renal epithelial cells, suggesting the EMT. The addition of 10 or 100 nM losartan in medium effectively attenuated the EMT of renal epithelial cells induced by 50 mmHg hydrostatic pressure loading. Our in vivo and ex vivo experimental data suggest that losartan treatment, even at a low dose can effectively alleviate renal fibrosis in mouse UUO model, at least partly by inhibiting the biomechanical stress-induced EMT of renal epithelial cells. A low dose of ARBs may repurpose for renal fibrosis treatment.

Inhibition of Autophagy in Renal Cells With Human, Urine-derived, Stem-cell Exosomes to Improve Diabetic Nephropathy.

Context: Clinicians can use stem cells to repair kidney injury. The kidneys' exosome secretions hold the secret to this therapeutic impact. Exosomes from urine-derived stem cells can prevent and treat glomerular damage that diabetes can cause, but the underlying process has remained a mystery. Objective: The study aimed to investigate the protective impact of exosomes from urine-derived stem cells (USCs) against diabetic nephropathy (DN) and to determine the mechanisms involved. Design: The research team performed an animal study. Setting: The study took place at the Affiliated Hospital of Jiujiang University in Jiujiang, Jiangxi, China. Animals: The animals were rats, SD male rats, weighing 200-220g, 40 animals, purchased from Weitong Lihua Experimental Animal Technology Co., Ltd. (certificate number: SCXK (Beijing) 2021-0006). Intervention: Except for a control group, the rats in the groups had induced DN. The five groups, with 10 rats each, were: (1) the negative control group, which received 0.2 ml of PBS solution; (2) the DN group, a second negative control group, which received 0.2 ml of PBS solution, (3) the inhibitor group, an intervention group that received 20 mg/kg of autophagy inhibitor; (4) the exosomes group, an intervention group that received 100 ug/kg of exosomes; and (5) the exosomes + inhibitor group, an intervention group that received 100 ug/kg of exosomes + 20 mg/kg of autophagy inhibitor. From week 8, for four weeks the team injected the inhibitor, exosomes, and exosomes + inhibitor groups with the appropriate treatments using the rats' tail veins. Outcome Measures: The research team: (1) examined the USCs in the exosomes of stem cells; (2) assessed the rats' weights and fasting blood glucose (FBG), using a blood glucose meter; (3) used Coomassie brilliant blue (CBB) staining to determine the amount of protein in the rats' urine and assessed their biochemical indexes; and (4) used Western blot (WB) and a quantitative polymerase chain reaction (Q-PCR) to detect autophagy and the signal transduction pathway. Results: Human exosomes from USCs alleviated injury in the rats that DN caused by reducing urinary-protein levels, serum creatinine (SCR), blood urea nitrogen (BUN), glomerular cell accumulation, and kidney weights. In rats with induced DN, the exosomes + inhibitor significantly reduced the activation of the mTOR signaling pathway, reduced the autophagy of their kidney cells, increased the protein expression of Bcl-2 in the kidney tissues, and lessened the damage to glomerular cells. Conclusions: Human urine-derived stem cell exosomes can significantly reduce the activation of the mTOR signaling pathway, reduce the autophagy of rats' kidney cells, increase the protein expression of LC3B in kidney tissues, and reduce the damage to glomerular cells. By blocking the mTOR signaling pathway, human urogenic exosomes can alleviate the signs and symptoms of DN.

Adsorption of chlortetracycline onto biochar derived from corn cob and sugarcane bagasse.

Biochar was prepared from two different types of biological waste materials, corn cob (CC) and sugarcane bagasse (SB). The adsorption capacity of each class of adsorbent was determined by chlortetracycline (CTC) adsorption tests. The adsorption kinetics and isotherms of chlortetracycline onto sugarcane bagasse biochar (SBB) and corn cob biochar (CCB) were studied. Experimental results indicated that pseudo-second-order adsorption kinetics of CTC onto SBB and CCB were more reasonable than pseudo-first-order kinetics, and the adsorption kinetic model of CTC onto SBB was slightly better than that onto CCB. The maximum adsorption capacity of CTC onto SBB was 16.96 mg/g at pH 4, while the highest adsorption efficiency of CTC onto CCB was achieved at pH 5 with a maximum adsorption of 12.39 mg/g. The Freundlich isotherm model was better than the Langmuir model at illustrating the adsorption process of CTC onto SBB and CCB. These results provide a way to understand the value of specific biochars, which can be used as efficient and effective adsorbents for CTC removal from waste-water. Compared with raw pinewood, SBB and CBB were considered as alternative materials to remove antibiotics from aqueous environments.

High-Performance Non-doped OLEDs with Nearly 100 % Exciton Use and Negligible Efficiency Roll-Off.

Non-doped organic light-emitting diodes (OLEDs) possess merits of higher stability and easier fabrication than doped devices. However, luminescent materials with high exciton use are generally unsuitable for non-doped OLEDs because of severe emission quenching and exciton annihilation in neat films. Herein, we wish to report a novel molecular design of integrating aggregation-induced delayed fluorescence (AIDF) moiety within host materials to explore efficient luminogens for non-doped OLEDs. By grafting 4-(phenoxazin-10-yl)benzoyl to common host materials, we develop a series of new luminescent materials with prominent AIDF property. Their neat films fluoresce strongly and can fully harvest both singlet and triplet excitons with suppressed exciton annihilation. Non-doped OLEDs of these AIDF luminogens exhibit excellent luminance (ca. 100000 cd m-2 ), outstanding external quantum efficiencies (21.4-22.6 %), negligible efficiency roll-off and improved operational stability. To the best of our knowledge, these are the most efficient non-doped OLEDs reported so far. This convenient and versatile molecular design is of high significance for the advance of non-doped OLEDs.

Spectroscopic and Theoretical Characterization of Through-Space Conjugation of Foldamers with a Tetraphenylethene Hinge.

Through-space conjugation is an important noncovalent interaction in artificial materials and biomacromolecules. Establishing relationships between geometry and property is of high significance to provide deeper insights into this phenomenon. In this work, we have focused on the through-space conjugation in a new class of foldamers with a folded tetraphenylethene core. We have studied its impact on the photophysical properties through experimental measurements and theoretical calculations. It is found that the through-space conjugation makes significant contributions to the short-wavelength absorption in these foldamers. Moreover, these foldamers exhibit aggregation-enhanced emission (AEE) and apparent blue shifts in their emission spectra on going from solution to aggregates. The structural changes are smaller in the aggregated state than those in the isolated state during the excited-state relaxation process, which results in lower re-organization energies. This accounts for the blueshifted and enhanced emissions in the aggregates.

Aggregation-enhanced emission active tetraphenylbenzene-cored efficient blue light emitter.

A tetraphenylbenzene (TPB) cored luminophore of TPB-AC with aggregation-enhanced emission characteristics was designed and synthesized. TPB-AC could be potentially applied for the fabrication of high performance organic light-emitting diodes (OLEDs) with blue light emission.

Highly Efficient Nondoped OLEDs with Negligible Efficiency Roll-Off Fabricated from Aggregation-Induced Delayed Fluorescence Luminogens.

Purely organic emitters that can efficiently utilize triplet excitons are highly desired to cut the cost of organic light-emitting diodes (OLEDs), but most of them require complicated doping techniques for their fabrication and suffer from severe efficiency roll-off. Herein, we developed novel luminogens with weak emission and negligible delayed fluorescence in solution but strong emission with prominent delayed components upon aggregate formation, giving rise to aggregation-induced delayed fluorescence (AIDF). The concentration-caused emission quenching and exciton annihilation are well-suppressed, which leads to high emission efficiencies and efficient exciton utilization in neat films. Their nondoped OLEDs provide excellent electroluminescence efficiencies of 59.1 cd A-1 , 65.7 lm W-1 , and 18.4 %, and a negligible current efficiency roll-off of 1.2 % at 1000 cd m-2 . Exploring AIDF luminogens for the construction of nondoped OLEDs could be a promising strategy to advance device efficiency and stability.

A Red to Near-IR Fluorogen: Aggregation-Induced Emission, Large Stokes Shift, High Solid Efficiency and Application in Cell-Imaging.

A tetraphenylethene (TPE) derivative modified with the strong electron acceptor 2-dicyano-methylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) was obtained in high yield by a simple two-step reaction. The resultant TPE-TCF showed evident aggregation-induced emission (AIE) features and pronounced solvatochromic behavior. Changing the solvent from apolar cyclohexane to highly polar acetonitrile, the emission peak shifted from 560 to 680 nm (120 nm redshift). In an acetonitrile solution and in the solid powder, the Stokes shifts are as large as 230 and 190 nm, respectively. The solid film emits red to near-IR (red-NIR) fluorescence with an emission peak at 670 nm and a quantum efficiency of 24.8 %. Taking the advantages of red-NIR emission and high efficiency, nanoparticles (NPs) of TPE-TCF were fabricated by using tat-modified 1,2-distearoylsn-glycero-3-phosphor-ethanol-amine-N-[methoxy-(polyethyl-eneglycol)-2000] as the encapsulation matrix. The obtained NPs showed perfect membrane penetrability and high fluorescent imaging quality of cell cytoplasm. Upon co-incubation with 4,6-diamidino-2-phenylindole (DAPI) in the presence of tritons, the capsulated TPE-TCF nanoparticles could enter into the nucleus and displayed similar staining properties to those of DAPI.

Modulation of aggregation-induced emission and electroluminescence of silole derivatives by a covalent bonding pattern.

The deciphering of structure-property relationships is of high importance to rational design of functional molecules and to explore their potential applications. In this work, a series of silole derivatives substituted with benzo[b]thiophene (BT) at the 2,5-positions of the silole ring are synthesized and characterized. The experimental investigation reveals that the covalent bonding through the 2-position of BT (2-BT) with silole ring allows a better conjugation of the backbone than that achieved though the 5-position of BT (5-BT), and results in totally different emission behaviors. The silole derivatives with 5-BT groups are weakly fluorescent in solutions, but are induced to emit intensely in aggregates, presenting excellent aggregation-induced emission (AIE) characteristics. Those with 2-BT groups can fluoresce more strongly in solutions, but no obvious emission enhancements are found in aggregates, suggesting they are not AIE-active. Theoretical calculations disclose that the good conjugation lowers the rotational motions of BT groups, which enables the molecules to emit more efficiently in solutions. But the well-conjugated planar backbone is prone to form strong intermoelcular interactions in aggregates, which decreases the emission efficiency. Non-doped organic light-emitting diodes (OLEDs) are fabricated by using these siloles as emitters. AIE-active silole derivatives show much better elecroluminescence properties than those without the AIE characterisic, demonstrating the advantage of AIE-active emitters in OLED applications.

Multichannel conductance of folded single-molecule wires aided by through-space conjugation.

Deciphering charge transport through multichannel pathways in single-molecule junctions is of high importance to construct nanoscale electronic devices and deepen insight into biological redox processes. Herein, we report two tailor-made folded single-molecule wires featuring intramolecular π-π stacking interactions. The scanning tunneling microscope (STM) based break-junction technique and theoretical calculations show that through-bond and through-space conjugations are integrated into one single-molecule wire, allowing for two simultaneous conducting channels in a single-molecule junction. These folded molecules with stable π-π stacking interaction offer conceptual advances in single-molecule multichannel conductance, and are perfect models for conductance studies in biological systems, organic thin films, and π-stacked columnar aggregates.

2,5-difluorenyl-substituted siloles for the fabrication of high-performance yellow organic light-emitting diodes.

2,3,4,5-Tetraarylsiloles are a class of important luminogenic materials with efficient solid-state emission and excellent electron-transport capacity. However, those exhibiting outstanding electroluminescence properties are still rare. In this work, bulky 9,9-dimethylfluorenyl, 9,9-diphenylfluorenyl, and 9,9'-spirobifluorenyl substituents were introduced into the 2,5-positions of silole rings. The resulting 2,5-difluorenyl-substituted siloles are thermally stable and have low-lying LUMO energy levels. Crystallographic analysis revealed that intramolecular π-π interactions are prone to form between 9,9'-spirobifluorene units and phenyl rings at the 3,4-positions of the silole ring. In the solution state, these new siloles show weak blue and green emission bands, arising from the fluorenyl groups and silole rings with a certain extension of π conjugation, respectively. With increasing substituent volume, intramolecular rotation is decreased, and thus the emissions of the present siloles gradually improved and they showed higher fluorescence quantum yields (Φ(F) =2.5-5.4%) than 2,3,4,5-tetraphenylsiloles. They are highly emissive in solid films, with dominant green to yellow emissions and good solid-state Φ(F) values (75-88%). Efficient organic light-emitting diodes were fabricated by adopting them as host emitters and gave high luminance, current efficiency, and power efficiency of up to 44,100 cd m(-2), 18.3 cd A(-1), and 15.7 lm W(-1), respectively. Notably, a maximum external quantum efficiency of 5.5% was achieved in an optimized device.

Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis.

Objective: This study is aimed at investigating diagnostic biomarkers associated with lipotoxicity and the molecular mechanisms underlying diabetic nephropathy (DN). Methods: The GSE96804 dataset from the Gene Expression Omnibus (GEO) database was utilized to identify differentially expressed genes (DEGs) in DN patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the DEGs. A protein-protein interaction (PPI) network was established to identify key genes linked to lipotoxicity in DN. Immune infiltration analysis was employed to identify immune cells with differential expression in DN and to assess the correlation between these immune cells and lipotoxicity-related hub genes. The findings were validated using the external dataset GSE104954. ROC analysis was performed to assess the diagnostic performance of the hub genes. The Gene set enrichment analysis (GSEA) enrichment method was utilized to analyze the key genes associated with lipotoxicity as mentioned above. Result: In this study, a total of 544 DEGs were identified. Among them, extracellular matrix (ECM), fatty acid metabolism, AGE-RAGE, and PI3K-Akt signaling pathways were significantly enriched. Combining the PPI network and lipotoxicity-related genes (LRGS), LUM and ALB were identified as lipotoxicity-related diagnostic biomarkers for DN. ROC analysis showed that the AUC values for LUM and ALB were 0.882 and 0.885, respectively. The AUC values for LUM and ALB validated in external datasets were 0.98 and 0.82, respectively. Immune infiltration analysis revealed significant changes in various immune cells during disease progression. Macrophages M2, mast cells activated, and neutrophils were significantly associated with all lipotoxicity-related hub genes. These key genes were enriched in fatty acid metabolism and extracellular matrix-related pathways. Conclusion: The identified lipotoxicity-related hub genes provide a deeper understanding of the development mechanisms of DN, potentially offering new theoretical foundations for the development of diagnostic biomarkers and therapeutic targets related to lipotoxicity in DN.

Effects of weight loss on QTc in people with obesity: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Overweight and obesity have been found to exhibit a statistically significant increase in corrected QT interval (QTc), a major contributing factor to sudden death. However, the influence of widely used weight loss strategies including diet, exercise, anti-obesity drugs, and bariatric surgery on QTc remains inconsistent. Therefore, the present systematic review and meta-analysis aim to quantitatively analyse and evaluate the effect of weight loss on QTc in obese patients after diet control with exercise intervention and anti-obesity drugs, as well as bariatric surgery. METHODS: Twenty randomised controlled trials (RCT) and observational studies were included in the meta-analysis on the effects of weight loss on QTc. The fixed-effects model was employed in the RCTs, and the random-effects model was employed due to the presence of statistical heterogeneity among observational studies. Subgroup analysis was conducted to understand the differences in distinct weight loss methods and follow-up time. RESULTS: Overall, the QTc of people with obesity after weight loss was shorter than that before (mean difference (MD) = 21.97 ms, 95% confidence interval (CI) = 12.42, 31.52, p < .0001). Subgroup analysis restricted to seven included studies whose intervention was diet control with exercise showed a decrease of QTc with statistical significance (MD = 9.35 ms, 95%CI = 2.56, 37.54, p = .007). In the remaining 11 studies, bariatric surgery was the weight loss method. The results also showed a shortening of QTc after surgery, and the difference was statistically significant (MD = 29.04 ms, 95%CI = -16.46, 41.62, p < .00001). A statistically significant difference in QTc shortening at 6 months compared to pre-operation values was further observed (MD = -31.01 ms, 95%CI = -2.89, -59.12, p = .03). The shortening of QTc at 12 months of follow-up was also significantly different from that before surgery (MD = 36.47 ms, 95%CI = 14.17, 58.78, p < .00001). Moreover, the differences became more pronounced as the follow-up time extended. CONCLUSIONS: We demonstrate that weight loss links to a shortened QTc, without considering the means of weight loss. Bariatric surgery has been found to result in a greater reduction in QTc.

Facile synthesis of the naturally cytotoxic triterpenoid saponin Patrinia-glycoside B-II and its conformer.

The first chemical synthesis of the natural triterpenoid saponin Patrinia-glycoside B-II, namely oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-gluco-pyranosyl-(1→3)]-α-L-arabinopyranoside, has been accomplished in a linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1C4 conformation of the arabinose residue was found to occur via conformational fluctuation during preparation of the intermediates. Molecular mechanism and quantum chemistry calculations showed that Patrinia-glycoside B-II and its conformer 1 cannot interconvert under normal conditions. Preliminary structure-activity relationships studies indicated that the 4C1 chair conformation of the arabinose residue in the unique α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl disaccharide moiety is one of the chief positive factors responsible for its cytotoxic activity against tumors.

Triptolide exposure induces oxidative stress and decreases oocyte quality in mouse.

Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 µg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.

Analysis of Immune and Inflammation Characteristics of Atherosclerosis from Different Sample Sources.

Background: Atherosclerosis is the predominant cause of cardiovascular diseases. Existing studies suggest that the development of atherosclerosis is closely related to inflammation and immunity, but whether there are differences and similarities between atherosclerosis occurring at different sites is still unknown. We elucidated the pathological characteristics of peripheral vascular diseases by using bioinformatic analyses on immune cells and inflammation-related gene expression in atherosclerotic arteries and plaques. Methods: Eight data sets regarding atherosclerosis were downloaded from the Gene Expression Omnibus database. Human immune genes were obtained from the IMMPORT website. The samples were scored and divided into high- and low-immune groups. Then the samples were analysed using weighted gene co-expression network analysis, while the modules were analysed using functional enrichment. The protein-protein interaction network was constructed using the STRING and Cytoscape databases. The hub immune genes were screened, and the correlation between hub immune genes and immune cells was analysed. Results: Immune cells and their functions were significantly different during atherosclerosis development. The infiltration proportion of immune cells was approximately similar in samples from different sources of patients with carotid atherosclerosis. However, the sensitivity of lower extremity atherosclerosis samples to immune cells is lower than that of carotid atherosclerosis samples.The samples from the plaque and artery were mainly infiltrated by macrophages, T cells and mast cells. After immune cells were assessed, resting NK cells, activated mast cells and M0 macrophages were found to be key immune cells in atherosclerosis and plaque formation. In addition, CCL4, TLR2, IL1B and PTPRC were considered to be immune marker genes in atherosclerosis development. Conclusion. Bioinformatic data analysis confirms the essential role of immune cells in cardiovascular diseases, and also indicates some differences of immune and inflammation characteristics of atherosclerosis between carotid and lower extremity arteries.

Identification of Aging-Related Genes Associated with Prognostic Value and Immune Microenvironment Characteristics in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a complex invasive tumour that occurs mainly among the elderly. Therefore, we analysed the relationship between ageing-related genes (AG) and DLBCL prognosis. Datasets related to DLBCL and human AGs were downloaded and screened from the Gene Expression Omnibus (GEO) database and HAGR website, respectively. LASSO and Cox regression were used to analyse AGs in the dataset and construct an AG predictive model related to DLBCL prognosis. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment were used to analyse the function of the AG predictive model. The immune microenvironment and immune cell infiltration in DLBCL and their relationship with the AG prediction model were also analysed. After the analysis, 118 AGs were identified as genes related to DLBCL prognosis. Using the LASSO and Cox regression analyses, 9 AGs (PLAU, IL7R, MYC, S100B, IGFBP3, NR3C1, PTK2, TBP, and CLOCK) were used to construct an AG prognostic model. In the training and verification sets, this model exhibited excellent predictive ability for the prognosis of patients with DLBCL who have different clinical characteristics. Further analysis revealed that the high- and low-risk groups of the AG prognostic model were significantly correlated with immune cell infiltration and tumour microenvironment in DLBCL. Functional enrichment analysis also showed that the genes in the AG model were associated with immune-related functions and pathways. In conclusion, we constructed an AG model with a strong predictive function in DLBCL, with the ability to predict the prognosis of patients with different clinical features. This model provides new ideas and potential therapeutic targets for the study of the pathogenesis of DLBCL.

Left abdominal wall proliferative myositis resection and patch repair: A case report.

BACKGROUND: Proliferative myositis is a rare benign tumor that is typically self-limiting and does not become malignant. It can be cured by simple resection without reported recurrence. Due to its rapid growth, hard structure and ill-defined borders, it can however be mistaken for malignant tumors such as sarcomas. CASE SUMMARY: We investigate the case of a 64-year-old male with proliferative myositis of the abdominal wall, who was preoperatively administered a needle aspiration biopsy and given a simple excision and patch repair. We then compared it with other similar cases to determine the effectiveness of this treatment method. CONCLUSION: Resection with follow-up observation has shown to be an effective treatment method for proliferative myositis. To avoid unnecessarily extended or destructive resection, a thorough and conclusive diagnosis is crucial, which requires adequate imaging and pathological knowledge.

Based on bioinformatics analysis lncrna SNHG5 modulates the function of vascular smooth muscle cells through mir-205-5p/SMAD4 in abdominal aortic aneurysm.

OBJECTIVE: The aim of this study was to explore expression profiles of long noncoding RNA (lncRNA)-messenger RNA (mRNA) in abdominal aortic aneurysm (AAA) patients. Further, we explored the mechanisms by which lncRNA SNHG5 modulates the function of vascular smooth muscle cells (VSMC) in AAA. METHODS: Human gene expression profile GSE57691 dataset, was retrieved from Gene Expression Omnibus database. The dataset included gene expression array data of 49 AAA patients and 10 control aortic specimens from organ donors. To explore the main roles of the biological network, differentially expressed lncRNA and mRNAs in the aortic aneurysm (AAA) and normal aortic specimens were determined. Differentially expressed lncRNA and mRNAs were then used to construct a competing endogenous RNA (ceRNA) network using Cytoscape software, and the five key lncRNA were identified. SNHG5 which was significantly downregulated in the AAA was chosen and analysis showed that it regulates mir-205-5p and SMAD4 by binding to mir-205-5p. Double luciferase reporter gene assays, RNA immunoprecipitation, and RNA knockdown studies were used to establish the relationship between SNHG5 and mir-205-5p. Apoptosis rate was determined using flow cytometry, whereas cell proliferation was evaluated using Edu, and 24 well Transwell assay. Western blot analysis was used to determine protein expression levels. RESULTS: The five differentially expressed lncRNAs were significantly correlated with 34 microRNAs and 112 mRNAs. mRNAs in the ceRNA network are implicated in protein binding, signal transduction, DNA and RNA transcription, development, and cell differentiation. SNHG5 was downregulated in the AAA and acts as a molecular sponge for mir-205. Downregulation of SNHG5 induces expression of mir-205-5p. Increased mir-205-5p expression level inhibits SMAD4 production, thus inhibiting proliferation and migration and promotes apoptosis of smooth muscle cells. CONCLUSION: Bioinformatics were used to explore molecular mechanism of AAA progression. The findings of this study show that lncRNA SNHG5 regulates proliferation and apoptosis of VSMC cells through modulation of the mir-205-5p/SMAD4 axis. Therefore, SNHG5 is a potential therapeutic target for AAA disease.

Five immune-gene-signatures participate in the development and pathogenesis of Kawasaki disease.

OBJECTIVE: To screen for immune genes that play a major role in Kawasaki disease and to investigate the pathogenesis of Kawasaki disease through bioinformatics analysis. METHODS: Kawasaki disease-related datasets GSE18606, GSE68004, and GSE73461 were downloaded from the Gene Expression Omnibus database. Three microarrays were integrated and standardized to include 173 Kawasaki disease samples and 101 normal samples. The samples were analyzed using CIBERSORT to obtain the infiltration of 22 immune cells and analyze the differential immune cells in the samples and correlations. The distribution of the samples was analyzed using principal component analysis (PCA). Immune-related genes were downloaded, extracted from the screened samples and analyzed for differential analysis (different expression genes [DEG]) and weighted gene co-expression network analysis (WGCNA). We constructed coexpression networks, and used the cytohobbe tool in Cytoscape to analyze the coexpression networks and select the immune genes that played a key role in them. RESULTS: Immune cell infiltration analysis showed that B cells naive, T cells CD8, natural killer (NK) cells activated, and so forth were highly expressed in normal samples. T cells CD4 memory activated, monocytes, neutrophils, and so forth were highly expressed in Kawasaki disease samples. PCA results showed a significant difference in the distribution of normal and Kawasaki disease samples. From the screened samples, 97 upregulated and 103 downregulated immune-related genes were extracted. WGCNA analysis of DEG yielded 10 gene modules, of which the three most relevant to Kawasaki disease were red, yellow, and gray modules. They were associated with cytokine regulation, T-cell activation, presentation of T-cell receptor signaling pathways, and NK cell-mediated cytotoxicity. CXCL8, CCL5, CCR7, CXCR3, and CCR1 were identified as key genes by constructing a coexpression network. CONCLUSION: Our study shows that we can distinguish normal samples from Kawasaki disease samples based on the infiltration of immune cells, and that CXCL8, CCL5, CCR7, CXCR3, and CCR1 may play important roles in the development of Kawasaki disease.