MiR-22 inhibits myocardial fibrosis in rats with myocardial infarction by targeting PTEN/Akt/mTOR signaling pathway.

This study aimed to evaluate the effects of miR-22 on myocardial fibrosis in rats with myocardial infarction (MI) and to further explore the possible underlying mechanism. A total of 80 rats were randomly divided into Sham group, miR-22 overexpression group, MI group or MI + miR-22 overexpression group. Reverse transcription-polymerase chain reaction (RT-PCR) results showed that compared with Sham group, miR-22 expression level in myocardial tissues of rats decreased significantly in MI group. Overexpression of miR-22 could remarkably relieve cardiac insufficiency in MI rats, increase EF% and FS%, and reduce collagen deposition and the mRNA expression level of fibrosis-promoting genes in myocardial tissues of MI rats. The cross-sectional area of myocardial cells in MI + miR-22 mimic group was smaller than that in MI group. According to the results of immunohistochemical staining, overexpression of miR-22 notably reduced the level of oxidative stress marker 4-HNE in myocardial tissues of MI rats. Meanwhile, myocardial cells in MI + miR-22 mimic group exhibited a prominently lower apoptosis rate than those in MI group. Furthermore, Western blotting results demonstrated that overexpression of miR-22 inhibited the activation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt/mTOR signaling pathway in myocardial tissues of MI rats. The inhibitory effects of miR-22 on myocardial fibrosis and hypertrophy after MI in rats may be related to its inhibition on the PTEN/Akt/mTOR signaling pathway. All our findings suggested that miR-22 is expected to become a targeted drug for the clinical treatment of MI.

Quantifying Waddington's epigenetic landscape: a comparison of single-cell potency measures.

MOTIVATION: Estimating differentiation potency of single cells is a task of great biological and clinical significance, as it may allow identification of normal and cancer stem cell phenotypes. However, very few single-cell potency models have been proposed, and their robustness and reliability across independent studies have not yet been fully assessed. RESULTS: Using nine independent single-cell RNA-Seq experiments, we here compare four different single-cell potency models to each other, in their ability to discriminate cells that ought to differ in terms of differentiation potency. Two of the potency models approximate potency via network entropy measures that integrate the single-cell RNA-Seq profile of a cell with a protein interaction network. The comparison between the four models reveals that integration of RNA-Seq data with a protein interaction network dramatically improves the robustness and reliability of single-cell potency estimates. We demonstrate that underlying this robustness is a correlation relationship, according to which high differentiation potency is positively associated with overexpression of network hubs. We further show that overexpressed network hubs are strongly enriched for ribosomal mitochondrial proteins, suggesting that their mRNA levels may provide a universal marker of a cell's potency. Thus, this study provides novel systems-biological insight into cellular potency and may provide a foundation for improved models of differentiation potency with far-reaching implications for the discovery of novel stem cell or progenitor cell phenotypes.

Optimization of Ultrasonic-Assisted Extraction of Active Components and Antioxidant Activity from Polygala tenuifolia: A Comparative Study of the Response Surface Methodology and Least Squares Support Vector Machine.

Dried roots of Polygala tenuifolia (YuanZhi in Chinese) are widely used in Chinese herbal medicine. These components in YuanZhi have significant anti-oxidation properties owing to high levels of 3,6'-disinapoylsucrose (DISS) and Polygalaxanthone III (PolyIII). In order to efficiently extract natural medicines, response surface methodology (RSM) and least squares support vector machine (LSSVM) were used for the modeling and optimization of ultrasound-assisted extraction of DISS and PolyIII together to determine the antioxidant activity of the extracts obtained from YuanZhi. For the optimal combination of the comprehensive yield of DISS and PolyIII (Y), the Box-Behnken design (BBD) was used to improve extraction time (X1), extraction temperature (X2), liquid-solid ratio (X3), and ethanol concentration (X4). The optimal process parameters were determined to be as follows: extraction time, 93 min; liquid-solid ratio, 40 mL/g; extraction temperature, 48 °C; and ethanol concentration, 67%. With these conditions, the predictive optimal combination comprehensive evaluation value is 13.0217. It was clear that the LS-SVM model had higher accuracy in predictive and optimization capabilities, with higher antioxidant activity and lower relative deviations values, than did RSM. Hence, the LS-SVM model proved to be more effective for the analysis and improvement of the extraction process.

UCHL1 regulates inflammation via MAPK and NF-κB pathways in LPS-activated macrophages.

Inflammation is a common pathophysiological process as well as a clinical threat that occurs in various diseases worldwide. It is well-documented that nuclear factor-κB (NF-κB) and mitogen-activated protein kinase pathways are involved in inflammatory reactions to microbial infections in lipopolysaccharide (LPS)-activated macrophages. The deubiquitinase ubiquitin carboxyl-terminal hydrolase-L1 (UCHL1) has been reported as an oncoprotein to promote the growth and progression of cancer cells. However, the regulatory mechanism of UCHL1 in inflammation is currently unclear. Here, we aimed to assess the effects of UCHL1 on LPS-associated inflammatory response in vitro and in vivo by enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction, and western blot analysis. This study identified that inhibition or knockdown of UCHL1 decreased the amounts of the key pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α in macrophages. Additionally, inhibition of UCHL1 suppressed LPS-induced extracellular signal-regulated protein kinase 1/2 phosphorylation and NF-κB translocation by regulating the inhibitor of NF-κB. Mechanically, UCHL1 interacts with IκBα protein in THP-1. Meanwhile, inhibition of UCHL1 blocked the LPS-induced degradation of IκBα through the ubiquitin-proteasome system. Moreover, in vivo assay showed that suppression of UCHL1 notably reduced the LPS-induced animal death and release of pro-inflammatory cytokines. Overall, the current findings uncover that UCHL1 functions as a crucial regulator for inflammatory response via reversing the degradation of IκBα, representing a potential target for the treatment of inflammatory diseases.

Status of hypoxia-inducible factor-1α expression in non-small cell lung cancer.

According to the latest statistics from WHO for all cancers, lung cancer tops the list with a 14.5% prevalence and a 22% death rate in men, similar to the prevalence in women, which is 13.8%. It is also the number one killer of cancer in China, with 40 in every 100,000 people suffering from lung cancer. HIF-1α is widely present in human cells in hypoxic environments. It regulates the body's response to hypoxia, cell oxygen balance, and hypoxia gene expression; participates in the proliferation and apoptosis of non-small cell lung cancer cells; participates in the invasion, metastasis, and neovascularization of tumor tissues; and affects the treatment and prognosis of non-small cell lung cancer. In view of the role of HIF-1α in the occurrence and development of non-small cell lung cancer, blocking HIF-1α by use of a single medication or combination chemotherapy has become a research hotspot. This review summarizes the role of HIF-1α in non-small cell lung cancer and provides new ideas for the treatment of this cancer type by synthesizing the research results of various authors.

The role of vascular endothelial growth factor in ischemic stroke.

Ischemic stroke is an injury caused by temporary or permanent cerebral vascular occlusion. It has a high incidence, mortality, and disability rate in clinical practice, and thus poses a considerable threat to public health as one of the top three major conditions endangering human health. Vascular endothelial growth factor is a specific mitogen of endothelial cells and a protein factor that is closely related to ischemic stroke. Vascular endothelial growth factor plays an important role in a multitude of physiological and pathological conditions. As a potential angiogenic protein for the treatment of ischemic stroke, vascular endothelial growth factor plays a role in promoting angiogenesis and neuroprotection and regeneration. At the same time, it plays a role in brain edema, collateral artery formation, and atherosclerosis. An increase in vascular endothelial growth factor levels contributes to the early pathological changes in patients with stroke and is closely related to the formation of cerebral edema in ischemic stroke complications. In theory, the neuroprotective and angiogenic effects of vascular endothelial growth factor make it an ideal candidate for the treatment of stroke. Here, we review the mechanism by which vascular endothelial growth factor participates in various stages of ischemic stroke and its prospects for use in the treatment of ischemic stroke.

Simultaneous Optimization for Ultrasound-Assisted Extraction and Antioxidant Activity of Flavonoids from Sophora flavescens Using Response Surface Methodology.

The ultrasonic-assisted extraction process and antioxidant activity of flavonoids from Sophora flavescens were investigated in this study. In order to optimize the extraction of flavonoids from Sophora flavescens, the influence of extraction time, methanol concentration, ultrasonic temperature, and solvent-to-material ratio was analyzed. Results showed that the extraction yields reached a maximum with the extraction time of 30 min, methanol concentration of 80%, temperature of 80 °C, and solvent-to-material ratio of 26 mL/g. The flavonoids were determined by HPLC, and the mean yields of trifolirhizin, formononetin, isoxanthohumol, maackiain, and kurarinone under the optimal conditions were 2.570, 0.213, 0.534, 0.797, and 3.091 mg/g, respectively. The evaluation of vitro antioxidant activity exhibited Sophora flavescens flavonoids had a strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging ability with IC50 of 0.984 and 1.084 mg/g, respectively. These results indicate that ultrasonic-assisted extraction is an efficient approach for the selective extraction of flavonoids, and response surface methodology further optimized the extraction.

Effect of GnRHR polymorphisms on in vitro fertilization and embryo transfer in patients with polycystic ovary syndrome.

We investigated the relationship between gonadotropin-releasing hormone receptor (GnRHR) gene polymorphisms and outcome of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). PCOS patients undergoing IVF-ET were selected, and infertile patients due to dysfunctional oviducts served as controls. GnRHR gene polymorphisms were detected using the polymerase chain reaction-restriction fragment length polymorphism assay. Gene-gene interaction and linkage disequilibrium tests were performed using the SHEsis software. Logistic regression analysis was performed to evaluate factors affecting outcome of patients undergoing IVF-ET. The PCOS group showed more patients with CC+CT genotypes rs12644822, rs3756159 and rs13138607 than the control group, and CC+CT genotypes and C alleles from three positions enhanced risk of PCOS. Patients with CC+CT genotypes from three positions exhibited increased serum luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), testosterone (T) and follicles than those with TT genotypes. The haplotype analysis indicated that CCC, CCT and TCC haplotypes increased the risk of PCOS, while TCT, TTC and TTT haplotypes lowered the risk. After IVF-ET treatment, patients with CC+CT genotypes of three positions in the GnRHR gene had a lower pregnancy rate than patients with TT genotypes. Logistic regression analysis indicated that CC+CT genotypes rs12644822, rs3756159 and rs13138607 were risk factor for patients undergoing IVF-ET. In conclusion, these findings demonstrate that CC+CT genotypes rs12644822C>T, rs3756159C>T and rs13138607C>T in the GnRHR gene may contribute to a decreased pregnancy rate for PCOS patients after IVF-ET.

Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese.

PURPOSE: The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese. METHODS: A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system. RESULTS: A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C9*3, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR*37 831-35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %. CONCLUSIONS: For the first time, the SNP POR*37 831-35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR*37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.

CXCL1/IGHG1 signaling enhances crosstalk between tumor cells and tumor-associated macrophages to promote MC-LR-induced colorectal cancer progression.

Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.

ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated (ECMO-RESCUE): study protocol for a prospective, multicentre, non-randomised cohort study.

INTRODUCTION: Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock. METHODS AND ANALYSIS: ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors' cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05184296.

MicroRNA-26 was decreased in rat cardiac hypertrophy model and may be a promising therapeutic target.

MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3ß (GSK3ß) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3ß expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3ß gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3ß signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.

Design, synthesis and biological evaluation of novel estrogen-derived steroid metal complexes.

A new series of estrogen-derived metal complexes were synthesized and characterized. The functionalized estrogen receptor ligands were prepared by a four-step synthetic strategy, and then three transition metal Pd, Ni, Zn were introduced readily to give the title metal complexes, in which the squaramide was introduced as ion acceptor for the first time in the development of estrogen-derived metal complexes for estrogen receptor. Upon binding to estrogen receptors, all of the estrogen conjugates exhibited acceptable binding affinity (up to 4.04% relative to estradiol), and in transcription assays, all the compounds are agonists on ERα. Molecular modeling studies suggest a structural basis for the agonist activity of these compounds.

Structural characterization, α-glucosidase inhibitory activity and antioxidant activity of neutral polysaccharide from apricot (Armeniaca Sibirica L. Lam) kernels.

Screening for α-glucosidase inhibitors and antioxidants from natural sources that could reduce postprandial glucose in diabetic patients and reduce oxidative stress had attracted considerable interest. In this study, a neutral polysaccharide (AP-1) with a triple helix structure was isolated and purified from the residue of apricot (Armeniaca sibirica L. Lam.) kernels by using DEAE-52 and Sephadex G-100 columns. The molecular weight of AP-1 was 23.408 kDa and consisted mainly of glucose with trace amounts of arabinose, galactose, and mannose, which had molar percentages of 98.48, 0.63, 0.62 and 0.27 %, respectively. The main chain of AP-1 was composed of →4)-α-D-Glcp-(1 â†’ interlinked, and α-D-Glcp-(1 â†’ was attached as a branched chain at the O-6 position of →4,6)-α-D-Glcp-(1→. In addition, AP-1 exhibited stronger α-glucosidase inhibition and free radical scavenging ability compared to crude polysaccharides. Therefore, AP-1 could be used as a potential natural hypoglycemic agent and antioxidant in the treatment of diabetes mellitus.

Characterization and biological function analysis of endogenous peptides derived from donkey colostrum proteins.

Donkey colostrum, due to its abundance of active ingredients, including lysozyme, proteins, and peptides, is essential for the growth and immune defence of newborns. However, research on endogenous peptides in donkey colostrum is inadequate. This study analysed the profiles of endogenous peptides, their potential bioactivity, and the enzymes that generated these peptides using two different strategies. A total of 6202 endogenous peptides were characterised through a database search, while an additional 2997 peptides were identified de novo. Among the 1142 proteins identified, trypsin and plasmin demonstrated the highest bioactivities. Furthermore, a bioinformatics-based screening identified antioxidant peptides, angiotensin I-converting enzyme inhibitory peptides, and dipeptidyl peptidase IV inhibitory peptides as the three most active peptides. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted. These findings enhance our knowledge of endogenous peptides in donkey colostrum and provide crucial information regarding these peptides as nutritional factors for the future development of functional foods derived from donkey sources.

[Study on the influence of buried thread nasal augmentation on dorsal soft tissue of nose and revision rhinoplasty].

Objective: To investigate the influence of buried thread nasal augmentation on dorsal soft tissue of nose and revision rhinoplasty. Methods: A clinical data of 29 patients requesting revision rhinoplasty after buried thread nasal augmentation, who were admitted between July 2017 and July 2019 and met the selection criteria, was retrospectively analyzed. All patients were female with an average age of 26.8 years (range, 18-43 years). The patiens were admitted to the hospital at 3-48 months after buried thread nasal augmentation (median, 15 months). Among them, there were 18 cases of insufficient nasal tip projection, 22 cases of insufficient nasal root projection, 7 cases of threads ectasia, 5 cases of threads exposure, 3 cases of infection, and 10 cases with two or more conditions. There were 9 cases of combined short nose deformity, 1 case of spherical hypertrophy of the nasal tip, 3 cases of deviation of the nasal columella, 3 cases of excessive width of the nasal base, and 1 case of nasal hump. Three infected patients only underwent threads removal and debridement. The rest patients underwent revision rhinoplasty, and the dorsum of the nose was made with polytetrafluoroethylene expansion; the tip of the nose was reshaped by taking autologous rib cartilage and alar cartilage in 16 cases, and by taking autologous septal cartilage and alar cartilage in another 10 cases. The threads and surrounding tissue specimens removed during operation were subjected to histologic observation. Nasal length and nasal tip projection were measured after revision rhinoplasty and the ratio was calculated to evaluate the nasal morphology; patient satisfaction was evaluated using the Likert 5-grade scale. Results: Patients were followed up 12-48 months (mean, 18 months). Inflammation was controlled in 3 patients with infections caused by buried thread nasal augmentation. The remaining 26 patients had satisfactory results immediately after revision rhinoplasty. Before revision rhinoplasty and at 7 days and 6 months after revision rhinoplasty, the nasal length was (4.11±0.34), (4.36±0.25), and (4.33±0.22) cm, respectively; the nasal tip projection was (2.34±0.25), (2.81±0.18), and (2.76±0.15) cm, respectively; and the nasal tip projection/nasal length ratio was 0.57±0.08, 0.65±0.05, and 0.64±0.04, respectively. There were significant differences in the nasal length and the nasal tip projection between time points ( P<0.05). There was a significant difference in the nasal tip projection/nasal length ratio between pre- and post-operation ( P<0.05), but there was no significant difference between 7 days and 6 months after operation ( P>0.05). The Likert score for satisfaction ranged from 1.5 to 5.0 (mean, 4.05). During follow-up period of 26 patients, no nasal prosthesis was exposed, and the shape of the nose was stable, and the nasal skin of 5 patients with exposed threads could be seen with different degrees of scarring; there was no infection, cartilage resorption, and no cartilage deformation, displacement, or exposure. Histological observation showed that absorbable threads were not only absorbed after implantation, but also with the prolongation of time, the inflammatory changes in the surrounding tissues caused by decomposition and absorption of the threads showed a gradual aggravation of the first, the heaviest inflammatory reaction in 6 to 12 months, and then gradually reduce the trend. Conclusion: After implantation of the absorbable thread into the subcutaneous tissue of the nasal dorsum, the nature of the thread is different from the body's own tissue, which will affect the soft tissue compliance of the nasal dorsum. The degradation and absorption of the thread will stimulate the infiltration of inflammatory cells and the proliferation of fibroblasts in the surrounding tissue and then form scar tissue, which will affect the design and effect of revision rhinoplasty.

Mono-(2-ethylhexyl) Phthalate (MEHP)-Induced Telomere Structure and Function Disorder Mediates Cell Cycle Dysregulation and Apoptosis via c-Myc and Its Upstream Transcription Factors in a Mouse Spermatogonia-Derived (GC-1) Cell Line.

As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related to reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result in an impaired telomere structure and function, which is associated with male infertility. However, the adverse effect of DEHP on telomeres in male reproductive cells has rarely been studied, and the related mechanisms remain unclear. In this study, we tested the effects of mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, on telomere dysfunction in mouse spermatogonia-derived cells (GC-1) and the potential role of TERT and c-Myc in MEHP-induced spermatogenic cell damage. Results showed that MEHP induced cell viability inhibition, G0/G1 phase cell cycle arrest, and apoptosis in GC-1 cells in a dose-dependent manner. Shortened telomeres, reduced telomerase activity, and decreased expression of TERT, c-Myc, and upstream transcription factors of c-Myc were also observed in the MEHP-treated cells. In conclusion, it can be concluded that TERT-mediated telomere dysfunction may contribute to MEHP-induced G0/G1 phase cell cycle arrest and apoptosis in GC-1 cells through the impairment of c-Myc and its upstream transcription factors.

[The effect and mechanism of Yiqi Tongluo Jiedu capsule against cerebral ischemia reperfusion injury].

To observe the effect and mechanism of Yiqi Tongluo Jiedu capsule aganist cerebral ischemia reperfusion injury, the SD rats were randomly divided into following groups: sham-operated group, model group, the group of low, medium and high dose of Yiqi Tongluo Jiedu capsule, and nimodipine group. Using focal middle cerebral artery embolization (MCAO) model, following items were observed: symptoms of neurological deficit score; infarct volume; activity of SOD, content of MDA and NO, activity of NOS of ischemic brain tissue; Bcl-2 and Bax protein expression; content of IL-1beta, IL-6 and TNFalpha in serum; IL-1beta mRNA expression of ischemic brain tissue. Results showed that Yiqi Tongluo Jiedu capsule could significantly reduce the symptoms of neurological deficits, promote the recovery symptoms of neurological deficits; narrow infarct volume of brain tissue obviously, reduce the percentage of infarct volume; raise activity of SOD, reduce content of MDA and NO, reduce activity of NOS; increase Bcl-2 protein, reduce Bax expression; reduce content of IL-1beta, IL-6 and TNFa in serum; reduce IL-1beta mRNA expression of ischemic brain tissue. Yiqi Tongluo Jiedu capsule has significant protective effects against ischemic brain injury, it has significant anti-apoptotic, antioxidant and anti-inflammatory effects.

RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice.

Background: Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-expression network in a cardiac hypertrophy mouse model after puerarin treatment. Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to analyze systematically mRNAs and lncRNAs expression. The target lncRNA were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression network were established to find the interaction of lncRNA and mRNAs. The biological process, cellular component, molecular function and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Results: Puerarin exhibited an obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC downregulated four lncRNAs, which could be revised by puerarin treatment (|log2 Fold change| > 2 and FDR < 0.05). Among them, expression alterations of lncRNA Airn (antisense of Igf2r non-protein coding RNA) was confirmed by qRT-PCR. Pearson's correlation coefficients of co-expression levels suggested that there was an interactive relationship between Airn and 2,387 mRNAs (r > 0.95 or r < -0.95). Those co-expressed mRNAs were enriched in some important biological processes such as translational initiation, cell proliferation, insulin-like growth factor binding and poly(A) RNA binding. KEGG analyses suggested that those Airn-interacted mRNAs were enriched in endocytosis, signaling pathways regulating pluripotency of stem cells and the Jak-STAT pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the lncRNAs/mRNAs co-expression network.

Helicobacter pylori infection induces stem cell-like properties in Correa cascade of gastric cancer.

Gastric cancer (GC) is the fourth leading cause of cancer-related death. Its poor prognosis is attributed to unclear pathogenesis. Currently, the most widely accepted model for elucidating the mechanism of GC is the Correa cascade, which covers several histological lesions of the gastric mucosa. GC stem cells (CSCs) are crucial for oncogenesis in the Correa cascade and GC progression. As Helicobacter pylori (H. pylori) is the etiological factor in the Correa cascade, growing evidence suggests that enhancement of gastric stem cell-like properties and increase in CSCs correlate with H. pylori infection. In this paper, we review recent studies that present pathogenic mechanisms by which H. pylori induces gastric stem cell-like properties and CSCs, which may supplement the existing Correa model of GC. First, the dysfunction of developmental signaling pathways associated with H. pylori infection leads to the enhancement of gastric stemness. Second, H. pylori infection promotes alteration of the gastric mucosal microenvironment. In addition, epithelial-mesenchymal transition (EMT) may contribute to H. pylori-induced gastric stemness. Taken together, understanding these pathogeneses will provide potential therapeutic targets for the treatment of CSCs and malignant GC in H. pylori induced-Correa cascade of GC.