Identification of key differentially expressed immune related genes in patients with persistent atrial fibrillation: an integrated bioinformation analysis.

OBJECTIVE: We aimed to investigate key differentially expressed immune related genes in persistent atrial fibrillation. METHODS: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) using "GEO query" package. "limma" package and "sva" package were used to conduct normalization and eliminate batch effects, respectively. We screened out differentially expressed genes (DEGs) based on "limma" package with the standard of |log fold change (FC)| ≥ 1.5 and false discovery rate (FDR) < 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed by "clusterProfler" package. We further applied LASSO to select key DEGs, and intersected key DEGs with immune related genes from ImmPort database. The ROC curve of each DEIRG was constructed to evaluate its diagnostic efficiency for AF. RESULTS: A total of 103 DEGs we were screened out, of them, 48 genes were down-regulated and 55 genes were up-regulated. Result of functional enrichment analysis show that, most of DEGs were related to immune response, inflammation, and oxidative stress. Ultimately, CYBB, RORB, S100A12, and CHGB were determined as key DEIRGs, each of which displayed a favor efficiency for diagnosing persistent AF. CONCLUSION: CYBB, RORB, S100A12, and CHGB were identified as key DEIRGs in persistent AF, and future studies are needed to further explore the underlying roles of CYBB, RORB, S100A12, and CHGB in persistent AF.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

The activation of CaN/NFAT signaling pathway in macrophages aggravated Lactobacillus casei cell wall extract-induced Kawasaki disease vasculitis.

OBJECTIVES: By using GWAS(genome-wide association studies) and linkage disequilibrium analysis to investigate the susceptibility genes of KD(Kawasaki disease), previous studies have identified that the CaN(calcineurin)-NFAT(the nuclear factor of activated T cell) signal pathway were significantly associated with susceptibility to KD. However, little is known about the molecular basis of the CaN/NFAT pathway involved in KD. Therefore, in our study we investigate the role of Ca2+/CaN/NFAT signaling pathway in macrophages in vitro and in vivo on coronary artery lesions induced by LCWE (Lactobacillus casei cell wall extract). METHODS AND RESULTS: We observed that LCWE could increase the expression of NFAT1 and NFAT2 in macrophages in vitro, and also enhance the transcriptional activity of NFAT by promoting the nucleus translocation. Similarly, in LCWE-induced mice model, the expression of NFAT1 and NFAT2 and associated proinflammatory factors were increased significantly. In addition, by knocking down or overexpressing NFAT1 or NFAT2 in macrophages, the results indicated that NFAT signaling pathway mediated LCWE-induced immune responses in macrophages and regulated the synthesis of IL(interleukin)-6, IL-1ß and TNF(tumor necrosis factor)-α in LCWE-induced macrophage activation. As well, we found that this process could be suppressed by CaN inhibitor CsA(cyclosporinA). CONCLUSIONS: Therefore, the CaN/NFAT signaling pathway mediated LCWE-induced immune responses in macrophages, and also participated in the LCWE-induced CALs(coronary artery lesions). And also the inhibitory effect of CsA in LCWE-induced cell model towards a strategy to modulate the CaN/NFAT pathway during the acute course of KD might be helpful in alleviate KD-induced CALs.

TCR repertoire landscape reveals macrophage-mediated clone deletion in endotoxin tolerance.

BACKGROUND: Endotoxin tolerance (ET) is a protective mechanism in the process of sepsis, septic shock, and their sequelae including uncontrolled inflammation. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what and how T-cell development contributes to ET inductions remain unclear. METHODS: Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of PBS was used as a control. We performed high-throughput sequencing to analyze the characteristics and changes of CD4+SP TCRß CDR3 repertoires with respect to V direct to J rearrangement during the ET induction. Moreover, the proportion and proliferation, as well as surface molecules such as CD80 and CD86, of F4/80+ macrophages were analyzed using FCM. Furthermore, ACT assay was designed and administered by the tail vein into murine LPS-induced mouse model to evaluate the role of F4/80+ macrophages on the development of CD4+SP thymocytes in ET condition. RESULTS: We found that the frequency and characteristics of the TCRß chain CDR3 changed obviously under condition of ET, indicating the occurrence of TCR rearrangement and thymocyte diversification. Moreover, the absolute numbers of F4/80+ macrophages, but not other APCs, were increased in thymic medulla at 72-h group, accompanied by the elevated function-related molecules of F4/80+ macrophages. Furthermore, adoptively transferred OVA332-339 peptide-loaded macrophages into Rag-1-/- mice induced the clone deletion of OVA-specific CD4+SP, thereby ameliorating the pathology in lung tissue in LPS challenge. CONCLUSIONS: These data reveal that the frequency and characteristics of the TCRß chain CDR3 undergo dynamic programming under conditions of LPS tolerance. Furthermore, the peripheral macrophages may be a key factor which carry peripheral antigen to thymic medulla and affect the negative selection of T-cell population, thereby contributing to the formation of ET. These results suggest that the clone selection in thymus in ET may confer protection against microbial sepsis.

C/EBPα/miR-7 Controls CD4+ T-Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice.

BACKGROUND AND AIMS: Increasing evidence in recent years has suggested that microRNA-7 (miR-7) is an important gene implicated in the development of various diseases including HCC. However, the role of miR-7 in autoimmune hepatitis (AIH) is unknown. APPROACH AND RESULTS: Herein, we showed that miR-7 deficiency led to exacerbated pathology in Concanavalin-A-induced murine acute autoimmune liver injury (ALI) model, accompanied by hyperactivation state of CD4+ T cells. Depletion of CD4+ T cells reduced the effect of miR-7 deficiency on the pathology of ALI. Interestingly, miR-7 deficiency elevated CD4+ T-cell activation, proliferation, and cytokine production in vitro. Adoptive cell transfer experiments showed that miR-7def CD4+ T cells could exacerbate the pathology of ALI. Further analysis showed that miR-7 expression was up-regulated in activated CD4+ T cells. Importantly, the transcription of pre-miR-7b, a major resource of mature miR-7 in CD4+ T cells, was dominantly dependent on transcription factor CCAAT enhancer binding protein alpha (C/EBPα), which binds to the core promoter region of the miR-7b gene. Global gene analysis showed that mitogen-activated protein kinase 4 (MAPK4) is a target of miR-7 in CD4+ T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4+ T cells with or without miR-7 deficiency. Our studies document the important role of miR-7 in the setting of AIH induced by Concanavalin-A. Specifically, we provide evidence that the C/EBPα/miR-7 axis negatively controls CD4+ T-cell activation and function through MAPK4, thereby orchestrating experimental AIH in mice. CONCLUSIONS: This study expands on the important role of miR-7 in liver-related diseases and reveals the value of the C/EBPα/miR-7 axis in CD4+ T-cell biological function for the pathogenesis of immune-mediated liver diseases.

Efficacy and safety of parenteral nutrition with iron sucrose for anemia prevention in preterm infants: A randomized, double-blind controlled study.

BACKGROUND AND OBJECTIVES: Our objective is to study the efficacy and safety of parenteral nutrition (PN) with iron sucrose to prevent anemia in preterm infants. METHODS AND STUDY DESIGN: We performed a randomized, double-blind controlled trial in which preterm infants were divided into five groups randomly: a control group (PN without iron sucrose, namely group Iron-0), and intervention groups (PN with iron sucrose 100 µg/kg/d, 200 µg/kg/d, 300 µg/kg/d and 400 µg/kg/d, namely group Iron-1, 2, 3, and 4, respectively). The indicators were red blood cell (RBC) parameters, iron storage and oxidant stress. RESULTS: One hundred infants completed this study. Excepting the RBC count in Iron-2, the value of erythrocyte parameters in intervention groups decreased less than that in the control group. And the decrease of RBC count in Iron-1 (-0.6×1012/L vs -0.9×1012/L, p=0.033), hemoglobin in Iron-4 (-26.0 g/L vs -41.0 g/L, p=0.03) and hematocrit in Iron-1(-9.5% vs -14.0%, p=0.014) was significantly less than in the control group. The change of ferritin in Iron-4 was significantly higher than in the control group (280 ng/ml vs 118 ng/ml, p=0.04). There was no difference in serum iron in intervention groups when compared to the control group (p>0.05). Except for the change of malondialdehyde (MDA) in Iron-1, the increase in other intervention groups was higher than in the control group (p>0.05). CONCLUSIONS: PN with iron sucrose for prevention of anemia in preterm infants is safe and efficacious to some extent.

Strain parameters for predicting the prognosis of non-ischemic dilated cardiomyopathy using cardiovascular magnetic resonance tissue feature tracking.

BACKGROUND: A considerable number of non-ischemic dilated cardiomyopathy (NDCM) patients had been found to have normalized left ventricular (LV) size and systolic function with tailored medical treatments. Accordingly, we aimed to evaluate if strain parameters assessed by cardiovascular magnetic resonance (CMR) feature tracking (FT) analysis could predict the NDCM recovery. METHODS: 79 newly diagnosed NDCM patients who underwent baseline and follow-up CMR scans were enrolled. Recovery was defined as a current normalized LV size and systolic function evaluated by CMR. RESULTS: Among 79 patients, 21 (27%) were confirmed recovered at a median follow-up of 36 months. Recovered patients presented with faster heart rates (HR) and larger body surface area (BSA) at baseline (P < 0.05). Compared to unrecovered patients, recovered pateints had a higher LV apical radial strain divided by basal radial strain (RSapi/bas) and a lower standard deviation of time to peak radial strain in 16 segments of the LV (SD16-TTPRS). According to a multivariate logistic regression model, RSapi/bas (P = 0.035) and SD16-TTPRS (P = 0.012) resulted as significant predictors for differentiation of recovered from unrecovered patients. The sensitivity and specificity of RSapi/bas and SD16-TTPRS for predicting recovered conditions were 76%, 67%, and 91%, 59%, with the area under the curve of 0.75 and 0.76, respectively. Further, Kaplan Meier survival analysis showed that patients with RSapi/bas ≥ 0.95% and SD16-FTPRS ≤ 111 ms had the highest recovery rate (65%, P = 0.027). CONCLUSIONS: RSapi/bas and CMR SD16-TTPRS may be used as non-invasive parameters for predicting LV recovery in NDCM. This finding may be beneficial for subsequent treatments and prognosis of NDCM patients. Registration number: ChiCTR-POC-17012586.

Long-term outcomes of various pediatric short bowel syndrome in China.

PURPOSE: The goal of this study was to analyze long-term outcome of various pediatric short bowel syndrome (SBS) at an intestinal rehabilitation center in China. METHODS: One hundred and fifty-seven children with SBS were enrolled in this study from October 1988 to July 2019. Their long-term follow-up outcome was analyzed according to the age of disease onset, parenteral nutrition (PN) duration, and anatomic types of short bowel, respectively. The clinical characteristics, which included demographics, the length of residual small bowel, PN duration, PN dependence, SBS-related complications such as IF-related liver disease (IFALD), catheter-related bloodstream infection (CRBI), and mortality were compared among the groups. RESULTS: The main etiology for SBS were intestinal atresia, NEC, and volvulus. Five of 157 patients did not wean off PN. The incidence of IFALD and CRBI was 24.2 and 22.3%, respectively. Sixteen cases died because of infection and liver failure and eight patients lost to follow-up. The survival rate of the 157 patients was 84.7%. PN duration was longer in the infants and children group (284 ± 457 d vs. 110 ± 64 d, P = 0.021; R = 0.264, P = 0.001) and more patients did not wean off PN than in the neonates group (11.6% vs. 0, P = 0.001; R = 0.295, P < 0.001). Patients with PN with a duration of longer than 90 days had more CRBIs (30.6%, P = 0.025; R = 0.236, P = 0.003). Additionally, the rate of CRBI was higher in patients with stoma (30.0%, P = 0.032). There was no difference in mortality among the groups. In five PN dependence patients, none was SBS onset in neonates. CONCLUSION: Pediatric patients with SBS could achieve favorable long-term survival and enteral autonomy. Different standards of SBS classification such as the age of disease onset, PN duration, and anatomic types of short bowel did not impact the overall mortality of pediatric SBS. Prolonged PN duration positively correlated with the age of disease onset and the incidence of CRBI. Patients with the complete continuity of intestinal tract suffered less from CRBI.

Risk factors of parenteral nutrition-associated cholestasis in very-low-birthweight infants.

AIM: We aimed to explore risk factors associated with parenteral nutrition-associated cholestasis (PNAC) in very-low-birthweight (VLBW) infants. METHODS: VLBW infants receiving parenteral nutrition (PN) for at least 14 days were enrolled in a retrospective dual-centre study and divided into two groups chronologically: group A (2000-2007) and group B (2008-2015). The incidence of PNAC and related factors were investigated. We compared the differences between PNAC and non-PNAC groups. A multivariate binary logistic regression analysis was carried out to identify the potential risk factors of PNAC. RESULTS: A total of 387 VLBW infants (53 in group A and 334 in group B) were enrolled in the study. The total incidence of PNAC was 6.7%, 9.4% in group A and 6.3% in group B. The dosage of amino acid (P = 0.009), glucose (P = 0.006), PN calories (P = 0.021) and the ratio of glucose/fat (P = 0.014) were significantly higher in group B than in group A. Non-protein energy to nitrogen ratio (P = 0.017) was lower in group B. Birthweight was significantly lower in the PNAC group than in the non-PNAC group (P = 0.021). Subgroup analysis showed that gestational age and duration of PN were significantly different between the PNAC and non-PNAC groups (P < 0.05). Logistic regression showed that prolonged duration of PN (≥43 days) (odds ratio 3.155, 95% confidence interval 1.009-9.861, P = 0.048) was an independent risk factor of PNAC. CONCLUSIONS: For VLBW infants, prolonged duration of PN is a risk factor for the development of PNAC. PNAC may be prevented by weaning off PN as early as possible in VLBW infants.

Evaluation of elevated left ventricular end diastolic pressure in patients with preserved ejection fraction using cardiac magnetic resonance.

OBJECTIVES: This study aims to validate the reliability of cardiac magnetic resonance (CMR) parameters for estimating left ventricular end diastolic pressure (LVEDP) in heart failure patients with preserved ejection fraction (HFpEF) and compare their accuracy to conventional echocardiographic ones, with reference to left heart catheterisation. METHODS: Sixty patients with exertional dyspnoea (New York Heart Association function class II to III) were consecutively enrolled. CMR-derived time-volume curve and deformation parameters, conventional echocardiographic diastolic indices as well as LVEDP evaluated by left heart catheterisation were collected and analysed. RESULTS: Fifty-one patients, who accomplished all three examinations, were divided into HFpEF group and non-HFpEF group based on LVEDP measurements. Compared to the non-HFpEF group, CMR-derived time-volume curve showed lower peak filling rate adjusted for end diastolic volume (PFR/EDV, p = 0.027), longer time to peak filling rate (T-PFR, p < 0.001), and increased T-PFR in one cardiac cycle (%T-PFR, p < 0.001) in HFpEF group. In multivariable linear regression analysis, %T-PFR (ß = 0.372, p = 0.024), left ventricular global peak longitudinal diastolic strain rate (LDSR, ß = -0.471, p = 0.006), and E/e' (ß = 0.547, p = 0.001) were independently associated with invasively measured LVEDP. The sensitivity and specificity of E/e' and LDSR for predicting the elevated LVEDP were 76%, 92% and 76%, 89%, respectively. CONCLUSIONS: These findings suggest that CMR-derived time-volume curve and strain indices could predict HFpEF patients. Not only E/e' assessed by echocardiography but also the CMR-derived %T-PFR and LDSR correlated well with LVEDP. These non-invasive parameters were validated to evaluate the left ventricular diastolic function. KEY POINTS: • The abnormal time-volume curve revealed insufficient early diastole in HFpEF patients. • Non-invasive parameters including E/e', %T-PFR, and LDSR correlated well with LVEDP.

Tolerogenic dendritic cells induced the enrichment of CD4+Foxp3+ regulatory T cells via TGF-ß in mesenteric lymph nodes of murine LPS-induced tolerance model.

Endotoxin tolerance is an important state for the prevention of lethal infection and inflammatory response, which is closely associated with the participation of innate immune cells. Moreover, mesenteric lymph nodes (MLNs)-resident immune cells, such as CD4+Foxp3+ regulatory T (Treg) cells and dendritic cells, play important roles in the maintenance of peripheral immune tolerance. However, the potential roles of these cells in MLNs in the development of endotoxin tolerance remain largely unknown. Recent research work showed that CD4+Foxp3+ Treg cells contributed to the development of endotoxin tolerance. Here, we further analyzed the possible change on CD4+Foxp3+Tregs population in MLNs in murine LPS-induced endotoxin tolerance model. Our data showed that the proportion and absolute number of CD4+Foxp3+Tregs, expressing altered levels of CTLA4 and GITR, significantly increased in MLNs of murine LPS-induced tolerance model. Moreover, the expression level of TGF-ß in MLNs also increased obviously. Furthermore, TGF-ß blockade could obviously reduce the proportion and absolute number of CD4+Foxp3+Tregs in MLNs and subsequently impair the protection effect against LPS rechallenge. Of note, we found that tolerogenic dendritic cell (Tol-DC), expressing lower levels of MHC-II and CD86 molecules, dominantly secreted TGF-ß in MLNs in murine LPS-induced tolerance model. In all, our data provided an unknown phenomenon that the total cell number of CD4+Foxp3+Tregs significantly increased in MLNs in endotoxin tolerance, which was related to MLN-resident TGF-ß secreting CD11c+DCs, providing a new fundamental basis for the understanding on the potential roles of MLN-resident immune cells in the development of endotoxin tolerance.

Strain Values of Left Ventricular Segments Reduce Non-homogeneously in Dilated Cardiomyopathy with Moderately and Severely Deteriorated Heart Function Assessed by MRI Tissue Tracking Imaging.

Changes of global and segmental ventricular strain at different deterioration levels of cardiac function in patients with dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR) have not yet been explored. In total, 101 patients diagnosed with DCM consecutively underwent CMR. They were categorized according to the reduction in left ventricular ejection fraction (LVEF) into the following groups: moderately reduced (n = 43) and severely reduced group (n = 58). LV global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), and segmental strain values were assessed using tissue tracking technique. LV segmental circumferential strain (CS) and radial strain (RS) in healthy volunteers increased from base to apex stepwisely. The LV base-to-apex increasing pattern disappeared in the moderate DCM group (RS: 26.61% ± 20.63% versus 21.97% ± 4.85% versus 29.05% ± 9.90%, P > 0.05; CS: -13.16% ± 6.40% versus -12.96%± 2.45% versus -15.32% ± 3.89%, P > 0.05). While in the severe group, CS and RS of base segment had the highest values, there was no significant difference between mid and apex segments. GLSLV, GRSLV, and GCSLV were significantly reduced in moderate and severe groups in steps, similar to the three parameters of RV. During a 17-month median follow-up, 25 patients had an index composite outcome event. GLSLV > -11.62%, GCSLV > -9.35%, and GRSLV≤ 12.42% were significantly associated with the occurrence of cardiac events in DCM patients. LV segmental values reduce non-homogeneously in DCM patients with moderately and severely deteriorated heart function.

Changes in macular sensitivity after half-dose photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the macular sensitivity changes after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR). METHODS: Eighteen patients (26 eyes) with chronic CSCR were recruited in the same hospital between April 2011 and December 2012. All patients were treated with one session of half-dose PDT after complete ophthalmic examination. Macular sensitivity examination was performed at baseline and 1, 3 and 6 months post-treatment. Mean sensitivity (MS) of the central 10 degrees (10°) and 4 degrees (4°), mean deviation (MD) and pattern standard deviation (PSD) on automated static perimetry (Humphrey Field Analyzer II-750) were used for analysis. RESULTS: There was significant improvement of the 10°MS from baseline (29.76 ± 1.51 dB) to 1 month (31.74 ± 1.56 dB), 3 months (31.51 ± 1.38 dB) and 6 months (31.19 ± 1.61 dB) after treatment (P < 0.001). The 4°MS was also significantly improved with half-dose PDT from baseline (28.96 ± 1.78 dB) to 1 month (32.41 ± 1.66 dB), 3 months (32.46 ± 1.50 dB) and 6 months (31.90 ± 1.84 dB) post-treatment (P < 0.001). MD was improved from baseline (-3.39 ± 0.89 dB) to 1 month (-1.96 ± 0.29 dB), 3 months (-1.94 ± 0.29 dB) and 6 months (-2.45 ± 0.13) post-treatment (P = 0.004). PSD also improved from 1.97 ± 0.24 dB at baseline to 1.47 ± 0.27 dB, 1.34 ± 0.24 dB, and 1.53 ± 0.24 dB (P = 0.001) at 1, 3 and 6 months after treatment, respectively. CONCLUSION: Macular sensitivity in CSCR can be improved by half-dose PDT, along with improvement of visual acuity and retinal thickness. The treatment outcome at 1 month may be a predictor of the final treatment response.

Use of the Conventional Side-viewing Duodenoscope for Successful Endoscopic Retrograde Cholangiopancreatography in Postgastrectomy Patients.

OBJECTIVES: The aim of this study was to evaluate the usefulness of the conventional side-viewing duodenoscope for successful endoscopic retrograde cholangiopancreatography (ERCP) in postgastrectomy patients. METHODS: A total of 220 consecutive patients with bile duct stones or a distal common bile duct stricture who had previously undergone gastrectomy and were referred for ERCP were analyzed for the outcome of their ERCP. All ERCP procedures were performed using a conventional side-viewing duodenoscope. In patients who had undergone a Billroth II gastroenterostomy and total gastrectomy with Roux-en-Y reconstruction, we also used the procedure of retrieval balloon-assisted enterography. RESULTS: The study group included 220 patients who had previously undergone gastrectomy (77 women and 143 men; mean age, 72.2 y; range, 11 to 93 y). The overall enterography success rate was 90.5% (199/220), and the diagnostic and ERCP success rates were both 88.6% (195/220). Endoscopy was unsuccessful in 21 patients who received Billroth II gastroenterostomy and Roux-en-Y reconstruction. After successful endoscopy, diagnostic and ERCP success was not achieved in 4 patients with Billroth II gastroenterostomy, with or without Braun anastomosis, due to cannulation failure. The procedure-related complication rate was 5.5% (12/220), including immediate bleeding (0.9%, 2/220), pancreatitis (4.1%, 9/220), and perforation (0.5%, 1/220). There were no procedure-related deaths. CONCLUSIONS: The side-viewing duodenoscope is a useful instrument for performing successful ERCP in patients postgastrectomy. In addition, retrieval balloon-assisted enterography may improve the enterography success rate in postgastrectomy patients with Billroth II and Roux-en-Y reconstruction.

Mutation in Actin γ-2 Responsible for Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in 4 Chinese Patients.

The aim of this study was to identify the underlying molecular mechanism for the development of megacystis microcolon intestinal hypoperistalsis syndrome in 4 Chinese patients. We found a c.770G>A (p.R257H) mutation in 3 patients, and a c.769C>T (p.R257C) mutation in the fourth patient by using whole-exome sequencing and targeted Sanger sequencing. The immunohistochemical investigation and transmission electron microscopy revealed an apparent defect of the intestinal smooth muscle, and hypoganglionosis. Our report suggested that R257 variant in the ACTG2 appear to be more frequent in populations of Asian ancestry; mutation of this locus could cause alterations of the intestinal and bladder smooth muscle filaments.

MicroRNA-7: a promising new target in cancer therapy.

The incidence of tumors with life-threatening effects has increased gradually over time; however, the mechanisms involved in tumor development have not been fully elucidated. Recent studies have shown that microRNA-7 (miR-7), which is endogenous non-coding RNA molecules of approximately 23 nucleotides, plays an important role in the occurrence and development of tumors as a key tumor suppressor. Mechanistic evidence showed that miR-7 is closely related to the growth, metastasis, and prognosis of various malignant tumors through regulating different target molecules, which suggest that miR-7 may be a new target for the clinical diagnosis and treatment of various tumors. In this review, we summarize current knowledge of the relationship between miR-7 and tumor development, diagnosis, and treatment.

Antisense oligonucleotides against microRNA-21 reduced the proliferation and migration of human colon carcinoma cells.

BACKGROUND: Colon carcinoma is one of the commonly tumors that threaten human beings as its highly morbidity and mortality. Recent evidences suggested that microRNA-21 (miR-21) played an important role in the development of colon carcinoma and might be a potential biological marker for the diagnosis and prognosis of colon carcinoma. However, the potential effect of miR-21 based therapeutic studies in colon carcinoma remains to be fully elucidated. METHODS: In present study, we constructed an eukaryotic expression vector encoding antisense oligonucleotides against miR-21 (termed as p-miR-21-ASO) and the expression of miRNA-21 in human colon cancer was detected by Real-time PCR. To assess its possible effect on the proliferation and migration capacity of human colon carcinoma cells in vitro, CCK-8 assay, colony formation assay and cell invasion, as well as migration assay, were performed respectively. Moreover, PTEN, one of target molecules of miRNA-21, was analyzed by Western blot and Fluorescence activated cell sorter assay. Finally, the transduction of AKT and ERK pathways in human colon carcinoma cells was determined by Western blot. RESULTS: We found that transiently transfection of p-miR-21-ASO could efficiently decrease the relative expression of miR-21 in human colon carcinoma HCT116 cells, accompanied by impaired proliferation and clone formation. Furthermore, we found that down-regulation of miR-21 also could significantly abrogate the invasion and migration capacity in vitro, as well as the expression of vascular endothelial growth factor which is critical for the metastatic capacity of colon carcinoma cells. Mechanistic evidence showed that down-regulation of miR-21 increased the expression of its target molecule PTEN in HCT116 cells. Finally, we revealed that the expression level of both phosphor-ERK1/2 and phosphor-AKT also were altered. CONCLUSIONS: Therefore, our data suggested miR-21 ASO against miR-21 might be a useful strategy to alter the expression of miR-21 in colon carcinoma cells, which was helpful for the development of miR-21-based therapeutic strategies against clinical colon carcinoma.

Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007-2018.

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study. Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status. Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty. Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.

The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.

The EphrinB2/EphB4 signaling pathway involves the regulation of vascular morphogenesis and angiogenesis. However, little is known about EphrinB2/EphB4 in the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysm formation. Hence, this study aimed to explore the role of EphrinB2/EphB4 and the potential therapeutic effect of EphrinB2-Fc in the coronary arterial endothelial injury of KD. The levels of EphB4 were compared between KD patients and healthy children. Human coronary artery endothelial cells (HCAECs) were stimulated with sera from acute KD patients to establish the KD cell model. The overexpression of EphB4 or treatment with EphrinB2-Fc was found to intervene in the cell model. The cell migration, angiogenesis, and proliferation ability were assessed, and the expression of inflammation-related factors was measured. Our study showed that EphB4 showed low expression in both KD patients and the cell model of KD. The EphB4 protein levels in the CECs of CAA+ KD patients were much lower than those in healthy children. EphrinB2-Fc treatment of KD sera-activated HCAECs suppressed cell proliferation, reduced the expression of inflammation-related factors (such as IL-6 and P-selectin), and elevated cell angiogenesis ability. The results reveal that EphrinB2-Fc has a protective function in endothelial cells and has promising clinical applications for protecting vascular endothelium in patients with KD.

Regulatory mechanism of fibrosis-related genes in patients with heart failure.

Background: Heart failure (HF) is a complex clinical syndrome characterized by the inability to match cardiac output with metabolic needs. Research on regulatory mechanism of fibrosis-related genes in patients with HF is very limited. In order to understand the mechanism of fibrosis in the development and progression of HF, fibrosis -related hub genes in HF are screened and verified. Methods: RNA sequencing data was obtained from the Gene Expression Omnibus (GEO) cohorts to identify differentially expressed genes (DEGs). Thereafter, fibrosis-related genes were obtained from the GSEA database and that associated with HF were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis was carried out to analyze the biological function of fibrosis-related DEGs. The protein-protein interaction (PPI) network of hub genes was constructed via the STRING database. Moreover, the diagnostic value of hub genes for HF was confirmed using ROC curves and expression analysis. Finally, quantitative real time PCR was used to detect the expression levels of mRNAs. Results: A total of 3, 469 DEGs were identified closely related to HF, and 1, 187 fibrosis-related DEGs were obtained and analyzed for GO and KEGG enrichment. The enrichment results of fibrosis-related DEGs were consistent with that of DEGs. A total of 10 hub genes (PPARG, KRAS, JUN, IL10, TLR4, STAT3, CXCL8, CCL2, IL6, IL1ß) were selected via the PPI network. Receiver operating characteristic curve analysis was estimated in the test cohort, and 6 genes (PPARG, KRAS, JUN, IL10, TLR4, STAT3) with AUC more than 0.7 were identified as diagnosis genes. Moreover, miRNA-mRNA and TF-mRNA regulatory networks were constructed. Finally, quantitative real time PCR revealed these 6 genes may be used as the potential diagnostic biomarkers of HF. Conclusion: In this study, 10 fibrosis-related hub genes in the HF were identified and 6 of them were demonstrated as potential diagnostic biomarkers for HF.