Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

[Research advances in genetic polymorphisms in Kawasaki disease]. / å·å´Žç— åŸºå› å¤šæ€æ€§çš„ç ”ç©¶è¿›å±•.

Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.

Treatment of posterior interosseous nerve entrapment syndrome with ultrasound-guided hydrodissection: A case report.

BACKGROUND: Posterior interosseous nerve (PIN) entrapment syndrome is one of the causes of weakness and pain of the arm muscles, which is prone to missed diagnosis and misdiagnosis in clinic practice. This paper reports a case of PIN entrapment syndrome, with PIN injury indicated by electrophysiology. Musculoskeletal ultrasound was applied to identify that the entrapment point was located at the inlet of the Frohse arch and the outlet of the supinator muscle. Treatment with ultrasound-guided nerve hydrodissection was performed on the entrapment point, which significantly improved the symptoms. Ultrasound-guided nerve hydrodissection is an effective therapeutic method for PIN entrapment syndrome. CASE SUMMARY: A male patient, 35 years old, worked as an automobile mechanic. He felt slightly weak extension activity of his right fingers 2 years ago but sought no treatment. Later, the symptoms gradually became aggravated and led to finger drop, particularly severe in the right middle finger, accompanied by supination weakness of the right forearm. Neural electrophysiological examination showed that the patient had partial PIN injury of the right radius. Musculoskeletal ultrasound examination indicated PIN entrapment at the inlet of the Frohse arch and the outlet of the supinator muscle. Therefore, PIN entrapment syndrome was diagnosed. After treatment with ultrasound-guided nerve hydrodissection around the entrapment point, the dorsiflexion weakness of the right hand was significantly improved compared with before treatment. CONCLUSION: Ultrasound-guided hydrodissection is efficacious for PIN entrapment syndrome, with high clinical value and great application prospects.

Effect of Ammonia-Oxidizing Bacterial Strains That Coexist in Rhizosphere Soil on Italian Ryegrass Regrowth.

Potted Italian ryegrasses (Lolium multiflorum L.) were used to investigate the effect of ammonia-oxidizing bacterial (AOB) strain that coexisted in rhizosphere soil on Italian ryegrass regrowth. The results showed that the isolated and screened AOB strain (S2_8_1) had 100% similarity to Ensifer sesbaniae. The inoculation of S2_8_1 on day 44 before defoliation caused its copy number in rhizosphere soils to increase by 83-157% from day 34 before defoliation to day 14 after defoliation compared with that in Italian ryegrass without S2_8_1 inoculation, indicating that S2_8_1 coexisted permanently with Italian ryegrass. The coexistence promoted the delivery of root-derived cytokinin to leaves and to increase its cytokinin concentrations; thus, the Italian ryegrass regrowth accelerated. During the 14-day regrowth period, the S2_8_1 coexistence with Italian ryegrass caused its leaf and xylem sap cytokinin concentrations, rhizosphere soil nitrification rates, net photosynthetic rates, and total biomass to increase by 38%, 58%, 105%, 18%, and 39% on day 14 after defoliation, respectively. The inoculation of S2_8_1 on day 2 before defoliation also increased the regrowth of Italian ryegrass. Thus, the coexistence of AOB with Italian ryegrass increased its regrowth by regulating the delivery of cytokinins from roots to leaves.

Fusion and expansion of vitellogenin vesicles during Caenorhabditis elegans intestinal senescence.

Some of the most conspicuous aging phenotypes of C. elegans are related to post-reproductive production of vitellogenins (Vtg), which form yolk protein (YP) complexes after processing and lipid loading. Vtg/YP levels show huge increases with age, and inhibition of this extends lifespan, but how subcellular and organism-wide distribution of these proteins changes with age has not been systematically explored. Here, this has been done to understand how vitellogenesis promotes aging. The age-associated changes of intestinal vitellogenin vesicles (VVs), pseudocoelomic yolk patches (PYPs), and gonadal yolk organelles (YOs) have been characterized by immuno-electron microscopy. We find that from reproductive adult day 2 (AD 2) to post-reproductive AD 6 and AD 9, intestinal VVs expand from 0.2 to 3-4 µm in diameter or by >3000 times in volume, PYPs increase by >3 times in YP concentration and volume, while YOs in oocytes shrink slightly from 0.5 to 0.4 µm in diameter or by 49% in volume. In AD 6 and AD 9 worms, mislocalized YOs found in the hypodermis, uterine cells, and the somatic gonadal sheath can reach a size of 10 µm across in the former two tissues. This remarkable size increase of VVs and that of mislocalized YOs in post-reproductive worms are accompanied by extensive fusion between these Vtg/YP-containing vesicular structures in somatic cells. In contrast, no fusion is seen between YOs in oocytes. We propose that in addition to the continued production of Vtg, excessive fusion between VVs and mislocalized YOs in the soma worsen the aging pathologies seen in C. elegans.

MdTCP46 interacts with MdABI5 to negatively regulate ABA signalling and drought response in apple.

TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors play crucial roles in plant abiotic stresses. However, little is known about the role of TCP genes in the drought stress tolerance of apple. Here, we found that abscisic acid (ABA) and drought treatment reduced the expression of MdTCP46, and overexpression of MdTCP46 reduced ABA sensitivity and drought stress resistance. MdTCP46 was found to interact with MdABI5 both in vitro and in vivo, and this interaction was essential for drought resistance via the ABA-dependent pathway. Overexpression of MdABI5 enhanced ABA sensitivity and drought stress resistance by directly activating the expression of MdEM6 and MdRD29A. MdTCP46 significantly suppressed the transcriptional activity of MdABI5, thereby negatively regulating MdABI5-mediated ABA signalling and drought response. Overall, our results demonstrate that the MdTCP46-MdABI5-MdEM6/MdRD29A regulatory module plays a key role in the modulation of ABA signalling and the drought stress response. These findings provide new insight into the role of MdTCP46 in ABA signalling and abiotic stress responses.

Time-economical synthesis of selenofunctionalized heterocycles via I2O5-mediated selenylative heterocyclization.

A time-economical and robust synthesis of various selenofunctionalized heterocycles was accomplished via I2O5-mediated selenocyclizations of olefins with diselenides. Using this method, 116 selenomethyl-substituted heterocycles were synthesized with up to 97% isolated yield in minutes. Additional features of this new protocol include the use of an inorganic oxidant, mild conditions, and easy operation. Preliminary investigations suggest that the transformation operates through selenenyl iodide-induced electrophilic cyclization.

A 67-bp variable duplication in the promoter region of the ADIPOQ is associated with milk traits in Xinjiang brown cattle.

Adiponectin, also known as ADIPOQ, is a hormone protein secreted by adipocytes. The ADIPOQ gene is expressed primarily in adipose tissue, and the encoded protein circulates in the bloodstream and has the potential to regulate both animal fat metabolism and hormone production. Our previous work uncovered a 67-bp variable duplication in the promoter region of ADIPOQ, which reduced the basal transcriptional activity of ADIPOQ in the 3T3_L1 cell and also inhibits the ADIPOQ mRNA expression in adipose tissue. Accordingly, the present study aimed to identify the relationship between the 67-bp structural variations in ADIPOQ promoter region and the milk traits of Xinjiang brown cattle (XJBC). The results revealed two genotypes, DD and ID, in the XJBC, and minor allelic frequency (MAF) for the 'I' allele was more than 1%. Moreover, the association analysis revealed that the 67-bp duplication in the promoter region of the ADIPOQ gene was significantly correlated with the 305 days of milk production volume, fat yield, and milk fat percentage in the XJBC (p < 0.05). These results obtained in this study suggested that the identified variable duplication could be considered as the potential genetic marker for improving milk traits of XJBC.

Aberrant H19 Expression Disrupts Ovarian Cyp17 and Testosterone Production and Is Associated with Polycystic Ovary Syndrome in Women.

As one of the most common endocrine disorders affecting women, polycystic ovary syndrome (PCOS) is associated with serious conditions including anovulation, endometrial cancer, infertility, hyperandrogenemia, and an increased risk for obesity and metabolic derangements. One contributing etiology to the pathophysiology of hyperandrogenemia associated with PCOS is an intrinsic alteration in ovarian steroidogenesis, leading to enhanced synthesis of androgens including testosterone. Studies have suggested that the increased testosterone synthesis seen in PCOS is driven in part by increased activity of CYP17A1, the rate-limiting enzyme for the formation of androgens in the gonads and adrenal cortex, which represents a critical factor driving enhanced testosterone secretion in PCOS. In this work, we evaluated the hypothesis that dysregulation of the noncoding RNA H19 results in aberrant CYP17 and testosterone production. To achieve this, we measured Cyp17 in ovarian tissues of H19 knockout mice, and quantified serum testosterone levels, in comparison with wild-type controls. We also evaluated circulating and ovarian H19 expression and correlated results with the presence or absence of PCOS in a group of women undergoing evaluation and treatment for infertility. We found that the loss of H19 in a mouse model results in decreased ovarian Cyp17, along with decreased serum testosterone in female mice. Moreover, utilizing serum samples and cumulus cells from women with PCOS, we showed that circulating and ovarian levels of H19 are increased in women with PCOS compared to controls. Findings from our multimodal experimental strategy, involving both a mouse model of dysregulated H19 expression and clinical serum and ovarian cellular samples from women with PCOS, suggest that the loss of H19 may disrupt androgen production via a Cyp17-mediated mechanism. Conversely, excess H19 may play a role in the pathogenesis of PCOS-associated hyperandrogenemia.

Atractylenolide­1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/c­kit signaling pathway.

Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in Sprague­Dawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide­1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow. Compared with the DGP group, atractylenolide­1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZ­induced group compared with the vehicle control group. Moreover, the STZ­induced group displayed downregulated expression levels of the DGP indicator KIT proto­oncogene, receptor tyrosine kinase (c­kit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stress­related markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide­1 significantly counteracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZ­induced DGP model rats. Further research indicated that atractylenolide­1 regulated oxidative stress reactions and improved gastric function by activating the SCF/c­kit signaling pathway. Collectively, the results of the present study suggested that atractylenolide­1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/c­kit signaling pathway, providing novel insights for the treatment of DGP.

The evaluation of genomic homozygosity for Xinjiang inbred population by SNP panels.

Xinjiang inbred cattle is a population which has been highly inbred for 45 years. However, the breed origin of this population cannot be traced back due to the lack of original records. To demonstrate the genetic background of Xinjiang inbred cattle, we analysed the worldwide genomic information of 16 cattle breeds using principal components analysis, and Admixture method. Furthermore, the shared SNP markers of Xinjiang inbred cattle, local Kazakh cattle, Holstein cattle, and Xinjiang Brown cattle were extracted to calculate population genetic parameters and genomic inbreeding indicators in order to evaluate the magnitude of inbreeding in each population. We also evaluated the relationship between inbreeding indicators and body size in the Xinjiang inbred population. Finally, the high frequency runs of homozygosity (ROH) regions for Xinjiang inbred cattle and local Kazakh population were selected for genes and QTL annotations. These results demonstrate that the ancestry proportions of inbreeding breed are similar to those of Kazakh cattle. The genomic homozygosity of Xinjiang inbred cattle is significantly higher than other populations; the inbreeding depression is observed in body size to a certain extent because body size decreased when corresponding homozygosity increased. Totally, six basic bio-pathways and 32 QTL regions that related to bovine economical traits were annotated. Our results provide the insights into breeding strategies, future protection, and utilization plan design for this special genetic material-Xinjiang inbred cattle.

Production of a specific monoclonal antibody for 1-naphthol based on novel hapten strategy and development of an easy-to-use ELISA in urine samples.

1-naphthol (1-NAP) is the main metabolite of pesticide carbaryl and naphthalene, and is also a genotoxic and carcinogenic intermediate in the synthesis of organic compound, dyes, pigment and pharmaceutical industry. In this work, two novel haptens were designed and synthesized for developing a competitive indirect enzyme-linked immunosorbent assay (ciELISA) method for 1-NAP in urine samples. The assay showed a limit of detection of 2.21 ng/mL and working range from 4.02 ng/mL to 31.25 ng/mL for 1-NAP in optimized working buffer. The matrix effect of samples was eliminated via 15-fold dilution of optimized working buffer. Good average recoveries (102.4%-123.4%) with a coefficient of variation from 11.7% to 14.7% was obtained for spiked urine samples. Subsequent instrument verification test showed good correlation between the results of ciELISA and high-performance liquid chromatography. The developed ciELISA is a high-throughput tool to monitor 1-NAP in urine, which can provide technical support for the establishment of biological exposure level for the exposure to carbaryl, naphthalene and other related pollutants.

Construction, expression and functional analysis of anti-clenbuterol codon-optimized scFv recombinant antibody.

The construction, expression and functional analysis of codon-optimized single-chain variable fragment (coscFv) against clenbuterol (CBL) prepared from the Escherichia coli system is described. First, the ionic concentration for coscFv expression was optimized through single-factor experiments. Then, the extraction conditions of inclusion bodies were optimized, and coscFv was affinity-purified. Finally, the functional analysis of coscFv was elucidated by indirect competitive enzyme-linked immunosorbent assay (icELISA) and molecular docking. After optimizing the ionic concentration, the yield of coscFv increased from 21.69% to 23.26%. The molecular weight of coscFv was determined to be approximately 27 kDa according to the SDS-PAGE and Western blot assay. The percentage of coscFv was as high as 43.9% after the inclusion bodies were extracted, washed, and dissolved. Functional analysis indicated that the coscFv recognized CBL, and the 50% inhibition average concentration of CBL (IC50) was 4.22 ± 0.01 (n = 3) ng/mL. The binding site between coscFv and CBL consisted of Asp33H, Met34H, Ser50H, Arg52H, Tyr57H, Leu59H, Asp99H, and Tyr93L. Our study confirms that coscFv can bind with CBL through the key amino acid residues and can be used to sensitively detect CBL.

Image quality and diagnostic value of ultra low-voltage, ultra low-contrast coronary CT angiography.

OBJECTIVE: To explore the image quality (IQ) and diagnostic value of 70 kVp turbo high-pitch coronary CT angiography (THP-CCTA) using automated tube voltage selection (ATVS) and 30 mL of low-concentration contrast agent. METHODS: Patients who underwent 70 kVp THP-CCTA using ATVS with 30 mL of contrast agent (group A) were prospectively enrolled, and those who underwent conventional CCTA (100/120 kVp, prospective sequential mode with 65-75 mL of contrast agent) (group B) were retrospectively selected for study. IQ was assessed subjectively on a 5-point scale, and diagnostic value was assessed based on invasive coronary angiography as the gold standard. Heart rate (HR), HR fluctuation (HRF), body mass index (BMI), effective radiation dose (ED), and iodine uptake (IU) were recorded. RESULTS: A total of 796 patients (398/398 in groups A/B) were included. Between-group differences in age, gender, BMI, HR, HRF, and IQ values were not significant. The ED/IU values were 0.3 ± 0.1 mSv/9.0 ± 0.0 g and 5.8 ± 1.8 mSv/22.9 ± 1.0 g in groups A and B, respectively (p < 0.01). The sensitivity, specificity, positive and negative predictive values, and accuracy of THP-CCTA for the diagnosis of ≥ 50% stenosis were 94.8%, 97.5%, 92.0%, 98.4%, and 96.9% respectively. The mean HR and coronary calcium score were independent predictors of diagnostic image quality, and the best cutoff values were 71.5 bpm and 444.1 respectively. CONCLUSION: This third-generation dual-source CT imaging modality, a 70-kVp THP-CCTA system using ATVS with 30 mL of low-concentration contrast agent, produces high-quality images with high diagnostic accuracy for significant stenosis, with ultra low ED and IU. This technique was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1. KEY POINTS: • Turbo high-pitch CCTA using 70 kVp via automated tube voltage selection and 30 mL of low-concentration contrast agent is feasible. • This protocol provides high diagnostic accuracy for significant coronary stenosis and reduces radiation doses and iodine uptake significantly. • This protocol was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1.

MicroRNA-488 inhibits endometrial glandular epithelial cell proliferation, migration, and invasion in endometriosis mice via Wnt by inhibiting FZD7.

Endometriosis is a chronic inflammatory syndrome and nearly 6%-10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR-488 would effectively inhibit the development of endometriosis. The microarray-based data analysis was performed to screen endometriosis-related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR-488 in mice with endometriosis, we measured miR-488 expression and expression levels of Frizzled-7 (FZD7), cyclinD1, ß-catenin, and c-Myc in vivo and in vitro. Finally, we detected the effect of miR-488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, ß-catenin, c-Myc and cyclinD1, and lower miR-488 expression in mouse endometrial tissues. FZD7 was the target gene of miR-488. Furthermore, elevated miR-488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of ß-catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up-regulated miR-488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down-regulating FZD7.

Community structure, dispersal ability and functional profiling of microbiome existing in fat body and ovary of the brown planthopper, Nilaparvata lugens.

The endosymbionts play vital roles in growth, development and reproduction in insects. Yeast-like endosymbionts (YLSs) have been well studied in Nilaparvata lugens (N. lugens), but little is known about the tissue-specific bacterial microbiomes, especially on the microbial intersection among internal tissues. Here, the correlation of microbial composition, structure, dispersal ability and functional profiling were illuminated in two tissues, the fat body and ovary in N. lugens. A total of 11 phyla and 105 genera were captured from all samples; Firmicutes and Proteobacteria were the most predominant and accounted for more than 99% in all samples. However, the relative abundance of Firmicutes and Proteobacteria was significantly different in ovary and fat body through Fisher's Least Significant Difference test. Microbial diversity but not the richness index in the two tissues exhibited significant difference. Furthermore, the microbial community structure of the ovary and fat body were primarily determined by tissue quality. Firmicutes showed strong dispersal ability between ovary and fat body based on the quantitative null model assessing, indicating the frequent interaction of these microbiomes in the two tissues. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways of microbial participation were delineated. The ten most abundant pathways counted for over 46% of the annotation and were shared between the two tissues, mainly containing Energy Metabolism and Amino Acid Metabolism/Biosynthesis. The results will provide insights into the correlation of microbial community structure between ovary and fat body of N. lugens.

Chromatin-regulatory genes served as potential therapeutic targets for patients with urothelial bladder carcinoma.

Urothelial bladder carcinoma is the ninth most common cancer in the world, with an estimated 150,000 deaths per year. Two comprehensive analysis based on The Cancer Genome Atlas urothelial bladder carcinoma reported that chromatin modifier gene mutations were common in bladder cancer. We aimed to find how the mutations and transcriptional profiles of the genes involving in chromatin modification affected the prognosis of patients. The data were retrieved from the Genomic Data Commons data portal and the gene list in pathway Chromatin Modifying Enzymes were obtained from Reactome. The expression levels and mutational profiles of the genes involving in the chromatin were utilized altogether to construct a fusion patient similarity network by similarity network fusion. The genes that were differentially expressed in one clustered group or two were identified. Fifty chromatin-regulating genes had nonsilent mutations in at least 10 patients. KMT2D, KDM6A, CREBBP, ARID1A, and ARID2 had enriched inactivating mutations. Among 399 cases where both the single-nucleotide polymorphism information and the messenger RNA expression profiles were available, 326, 23, and 50 patients were clustered into Groups 1, 2, and 3, respectively. The survival analysis suggested that the patients in these three groups had a different prognosis. Thity-one genes were identified as differentially expressed in any group. The Gene Ontology term enrichment showed that the differentially expressed genes were enriched in the immune response especially in the complement activation. Altogether, chromatin-regulatory genes were key in bladder cancer and can serve, with the differentially expressed genes, as potential therapeutic targets.

Hypermethylation of delta-like homolog 1/maternally expressed gene 3 loci in human umbilical veins: insights into offspring vascular dysfunction born after preeclampsia.

BACKGROUND: Increasing epidemiological studies have confirmed the association between maternal preeclampsia and elevated blood pressure in their offspring. Though case-control or cohort studies have demonstrated long-term outcomes for the offspring of preeclampsia, it is still a question that how these changes were caused by genetic reasons or by preeclampsia itself. OBJECTIVE: In our study, we explored the potential epigenetic regulation of delta-like homolog 1-maternally expressed gene 3 (DLK1-MEG3) region in human umbilical vein endothelial cells (HUVECs), and its connection with endothelium-derived factors. STUDY DESIGN: We recruited 58 singletons born with spontaneous conception (control group) and 67 singletons whose mother with preeclampsia (preeclampsia group), and detected the infants' blood pressure and growth development index. To explore the potential mechanism, we did real-time PCR to test DLK1-MEG3 imprinted genes and endothelium-derived factors. ELISA confirmed the protein secretion changes between two groups. In addition to confirm epigenetic alteration in preeclampsia HUVEC, we performed pyro-sequencing to detect methylation status of two different methylation regions: intergenic differential methylation region (IG-DMR) and MEG3 DMR which control the expression of DLK1 and MEG3. Furthermore, Person correlation was used to make sure the association of methylation alteration of IG-DMR and endothelium-derived factors. RESULTS: In our study, we found that DBP was significantly lower in preeclampsia offspring who born over 34 weeks compared with normal offspring (53.59 ±â€Š1.38 vs. 59.9 ±â€Š1.40 mmHg, P < 0.01), which leads to higher pulse pressure difference. Quantitative real-time PCR showed that imprinted gene DLK1 level significantly increased and MEG3 level decreased in HUVEC of preeclampsia group compared with control group, accompanying with lower expression of endothelial nitric oxide synthase and vascular endothelial growth factor (VEGF), higher expression of endothelin-1 (ET1), which are close related with vascular endothelial function. Meanwhile, ELISA assay of ET1, nitrite, VEGF were consistent with real-time results. Furthermore, abnormal expression of DLK1-MEG3 expression was caused by hypermethylation status of IG-DMR, And methylation status of IG-DMR highly correlated with ET1 concentration and nitrate concentration, these might be one of the mechanisms for impaired endothelial function (coefficient = 0.5806, P = 0.0115; coefficient = -0.4883, P = 0.0398). CONCLUSION: Our results demonstrated that altered expression of imprinted genes DLK1 and MEG3 were caused by hypermethylation of IG-DMR in HUVEC of preeclampsia group, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1. It might be one potential mechanism for higher risk of cardiovascular disease in preeclampsia offspring later in life.

Long noncoding RNA LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1.

Prostate cancer is one of the most frequent malignancies affecting men. Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However, the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell cycle progression. RNA sequencing analysis revealed that it regulates the expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down-regulation inhibits the expression of CCND1 and cell cycle progression, whereas these effects are abolished upon miR-541-3p suppression. In summary, our study revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Modulation of their levels may be used to treat prostate cancer.

Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children.

BACKGROUND: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. METHODS: The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. RESULTS: We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. CONCLUSION: Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma.