bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation and comparison of non‐hyperemic pressure reserve to fractional flow reserve for assessment of coronary artery stenosis: A real world study
Authors: Aoun Joe , Lahsaei Saba , Zahm Caroline , Bhat Tariq , Carrozza Joseph P.
Published: September 2018

Background

The visual interpretation of an angiographic stenosis may not always reflect the physiological significance of a lesion. Fractional Flow Reserve (FFR) is a reliable index to assess the significance of a lesion during hyperemia. However, there are pitfalls that can lead to significant misinterpretation and adverse events.

Objective

This study sought to evaluate the accuracy and predictability of the non‐hyperaemic pressure ratio (NHPR) without hyperemic stimuli, compared to hyperemic FFR.

Methods

We conducted a retrospective, multicenter study of 700 patients who underwent a pressure recording during coronary angiography using NHPR and FFR measurements. Receiver operator characteristic (ROC) curve was constructed. NHPR sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy test were calculated. The most accurate NHPR cutoff was determined.

Results

Of the 700 procedures, 449 cases were included. By ROC analysis, the optimal cut‐point for NHPR was 0.93 to predict an FFR of ≤0.80 with an overall diagnostic accuracy of 78.84%. The sensitivity of this NHPR cutoff was 85.06%, specificity of 75.59%, PPV of 64.53% and a NPV of 90.65%. There was an overall accuracy of about 80% for predicting non‐hyperemic index (FFR < 0.80) using a cutoff of NHPR ≤ 0.93.

Conclusions

The use of NHPR can be considered in certain clinical scenarios where adenosine is contraindicated or there are other challenges; with the knowledge that hyperemia might be necessary if there is any high clinical suspicion as it still remains the reference standard for diagnostic certainty.
Safety and efficacy of transcatheter aortic valve replacement for native aortic valve regurgitation: A systematic review and meta‐analysis
Authors: Rawasia Wasiq Faraz , Khan Muhammad Shahzeb , Usman Muhammad Shariq , Siddiqi Tariq Jamal , Mujeeb Firzah Abdul , Chundrigar Mohsin , Kalra Ankur , Alkhouli Mohamad , Kavinsky Clifford J , Bhatt Deepak L.
Published: September 2018

Objective

The objective of this study was to analyze the available literature on using transcatheter aortic valve replacement (TAVR) for native aortic regurgitation (AR).

Background

Surgical aortic valve replacement is the gold standard therapy for native AR. TAVR has emerged as an alternative approach in high‐risk patients.

Methods

MEDLINE, Scopus, and Cochrane CENTRAL were searched for reports of at least 5 patients undergoing TAVR for native AR. Outcomes included 30‐day mortality, myocardial infarction, stroke, major bleeding, postprocedural moderate to severe AR, and device success. Pooled estimates were calculated using a random‐effects model. Subgroup analysis and a meta‐regression were performed to study the effects of study level covariates on outcomes.

Results

Nineteen studies (n =998 patients) were included. The rate of procedural success per Valve Academic Research Consortium – 2 (VARC‐2) criteria was 86.2% (78.8%–92.2%]. Thirty‐day mortality was 11.9% (9.4%–14.7%). Subgroup analysis showed the use of new generation valves was associated with lower 30‐day mortality (P = 0.02) and higher device success (P = 0.009) compared with early generation valves. There was no significant difference (P = 0.13) in the rate of 30‐day mortality between patients receiving purpose‐specific [8.2% (4.3%−13.1%); I2 = 0%] and nonpurpose specific valves [13.0% (8.2%–18.6%); I2 = 25%]. However, device success was higher (P = 0.02) in patients who received purpose‐specific valves [96.3% (92.2%−98.9%); I2 = 0%] compared with nonpurpose specific valves [84.4% (75%−91.9%); I2 =46%].

Conclusion

TAVR for native AR is associated with acceptable procedural success but increased early mortality. However, the safety and the efficacy of the procedure increased with newer valves.
Post/preprocedural ratio of hemodynamically assessed aortic regurgitation index as a marker for the need for corrective measures during transcatheter valve replacement: A first confirmatory study in patients receiving a new generation transcatheter self‐expandable prosthesis
Authors: Mas‐Peiro Silvia , Weiler Helge , Papadopoulos Nestoras , Zeiher Andreas M. , Fichtlscherer Stephan , Vasa‐Nicotera Mariuca
Published: September 2018

Objectives

We aimed to investigate the value of post/preprocedural aortic regurgitation index (ARI) ratio as a marker for more‐than‐mild aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) and as an indication of the need for corrective measures, provided that the implantation depth was acceptable.

Background

Post/preprocedural ARI increases accuracy of residual AR assessment by considering hemodynamic status prior to TAVR.

Methods

ARI ratio was calculated in 70 patients undergoing TAVR. ARI ratios were defined as post/preprocedural ARI (ARI ratio 1), and as postcorrective measure/preprocedural ARI (ARI ratio 2). Intraprocedurally, corrective measures use was decided based on angiographically assessed AR severity. The relationship of such decisions to ARI ratios based on a recently proposed threshold (ARI ratio < 0.6) was evaluated. ARI ratios in corrected versus noncorrected patients and precorrection versus postcorrection values were assessed.

Results

Overall, mean (±SD) ARI ratio 1 (n = 70) was 0.81 (±0.36). Corrective measures were used in 22 patients (31.4%). Mean ARI ratio 1 in such patients was 0.55 (±0.25) versus 0.93 (±0.34) in the 48 noncorrected patients (P < 0.0001). Mean ARI ratio 1 in 21 patients requiring postdilation was 0.56 (±0.25), which was below the previously suggested 0.6 threshold. After postdilation, ARI ratio 2 increased to 0.85 (±0.16) (P < 0.0001), with all patients showing an ARI ratio 2 ≥ 0.6.

Conclusions

ARI ratio is closely related to intraprocedural decisions to perform corrective measures based on angiography. Routine use of intraprocedural ARI ratio could be useful as a complementary quantitative marker for residual AR and for the need for corrective measures.
Trends in volume and risk profiles of patients undergoing isolated surgical and transcatheter aortic valve replacement
Authors: Mori Makoto , Bin Mahmood Syed Usman , Geirsson Arnar , Yun James J. , Cleman Michael W. , Forrest John K. , Mangi Abeel A.
Published: September 2018

Background

Recent reports describe increases in the case volume of surgical aortic valve replacement (SAVR) after centers establish a transcatheter aortic valve replacement (TAVR) program. We investigate contemporary temporal trends in SAVR and TAVR case volumes and risk profiles at a high volume academic medical center.

Methods

We conducted a retrospective, descriptive evaluation of consecutive patients who underwent TAVR (n = 538) or SAVR (n = 657) in 2011–2016. The STS predicted risk of mortality (PROM) for isolated SAVR was used to calculate PROM for both SAVR and TAVR patients. Patients were stratified based on STS PROM as follows: low risk (<4%), intermediate risk (4–8%), and high risk (≥8%). Temporal changes in patient risk‐profile were characterized descriptively.

Results

Median STS PROM for the study period was 6.3% and 2.0% for TAVR and SAVR cohorts, respectively (P < 0.001). Since 2011, TAVR volume consistently increased, while SAVR volume increased initially, peaking in 2013 and steadily declined. The STS PROM for SAVR remained stable during the entire study period, while that for TAVR showed a steady decline. The proportions of intermediate and low STS PROM patients undergoing TAVR increased. Proportions of each risk category in SAVR cohort remained stable over time.

Conclusions

SAVR volume increased initially but declined eventually following the implementation of TAVR program. The distribution of the STS PROM in TAVR cohort changed dramatically with increasing proportion of patients in lower risk categories. These findings suggest the converging patient populations in TAVR and SAVR, which may be associated with the decline in the overall SAVR volume.
Novel predictor of target vessel revascularization after coronary stent implantation: Intraluminal intensity of blood speckle on intravascular ultrasound
Authors: Saito Yuichi , Kitahara Hideki , Okuya Yoshiyuki , Nakayama Takashi , Fujimoto Yoshihide , Kobayashi Yoshio
Published: September 2018

Background

The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter‐intravascular ultrasound (IB‐IVUS) across the coronary artery stenosis (i.e., ΔIBS) has been reported to negatively correlate with fractional flow reserve. Fractional flow reserve after coronary stenting is known as a predictor of target vessel revascularization (TVR). However, the relation between ΔIBS and TVR is unclear.

Methods

Seven hundred and three vessels which underwent percutaneous coronary intervention with stents were screened. Vessels without IVUS‐guidance and follow‐up information were excluded. Intraluminal IBS values were measured using IB‐IVUS in cross‐sections at the ostium of the target vessel and at the distal reference of implanted stent. ΔIBS was calculated as (distal IBS) − (ostium IBS).

Results

A total of 393 vessels were included. Mean ΔIBS at postprocedure was 6.22 ± 5.65. During the follow‐up period (11.2 ± 3.1 months), 24 cases (6.1%) had TVR. ΔIBS was significantly greater in the vessels with TVR than in those without (11.10 ± 5.93 vs. 5.90 ± 5.49, P <0.001). In receiver operating characteristic curve analysis, ΔIBS significantly predicted TVR (AUC 0.74, best cut‐off value 8.24, P < 0.001). Multiple logistic regression analysis showed use of drug eluting stent and ΔIBS ≥ 8.24 as independent predictors of TVR.

Conclusions

ΔIBS at postprocedure was significantly associated with TVR. IVUS may be able to predict TVR by physiological assessment with measurement of ΔIBS.
Time‐dependent benefits of pre‐treatment with new oral P2Y12‐inhibitors in patients addressed to primary PCI for acute ST‐elevation myocardial infarction
Authors: Pepe Martino , Cafaro Alessandro , Paradies Valeria , Signore Nicola , Addabbo Francesco , Bortone Alessandro Santo , Navarese Eliano Pio , Contegiacomo Gaetano , Forleo Cinzia , Bartolomucci Francesco , Di Cillo Ottavio , Bianchi Francesco Paolo , Zanna Domenico , Favale Stefano
Published: September 2018

Objectives

The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12‐inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the loading dose (LD) administration.

Background

The goal of ST‐elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12‐Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration.

Methods

The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of “P2Y12‐I LD administration‐to‐balloon time”: Group 2 included patients that received P2Y12‐I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre‐ and post‐pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment.

Results

Pre‐pPCI TFG improved with increasing P2Y12‐I LD administration‐to‐balloon time; pre‐PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P < 0.002). Post‐pPCI TFG 3 results also differed significantly between the three groups: 85.2% in Group 0, 88.1% in Group 1, 97.6% in Group 2 (P < 0.013). ST resolution rates were also positively associated with longer pretreatment intervals.

Conclusions

This observational study suggests that the angiographic benefit of P2Y12‐I administration is time‐dependent: longer pretreatment improves coronary reperfusion in terms of pre‐ and post‐pPCI TFG and STR.
Intracardiac echography for left atrial appendage closure: A step‐by‐step tutorial
Authors: Paiva Luis V. , Costa Marco P. , Barra Sérgio C. , Gonçalves Lino
Published: September 2018

Objectives

We sought to provide a practical educational tool for the utilization of intracardiac echography (ICE) in the left atrium for the percutaneous closure of the left atrial appendage (LAA).

Background

Although transesophageal echocardiography (TEE) is the gold‐standard imaging technique for LAA closure, ICE is stepping in to support noncoronary cardiology interventions by improving workflow and case turnover and may be more adequate for frail patients with significant and multiple comorbidities.

Methods

This article discusses the utility of ICE for LAA closure, its advantages compared to TEE, contraindications to TEE use and offers an extensive illustration of the main steps of the procedure.

Conclusions

The use of ICE in the left atrium allows a feasible guidance of all steps of the percutaneous closure of LAA.
Standardized bench test evaluation of coronary stents: Biomechanical characteristics
Authors: Bonin Mickael , Guerin Patrice , Olive Jean Marc , Jordana Fabienne , Huchet François
Published: September 2018

Objectives

The purpose of the study was to develop a standardized and global bench test protocol to evaluate the biomechanical characteristics of the most currently used drug‐eluting coronary stents.

Background

The use of coronary stents has contributed to the reduction of cardiovascular mortality but can be associated with specific complications. Improving the biomechanical matching between the stents and the coronary anatomy may reduce these complications.

Methods

We assessed five commercially available drug‐eluting stents: the Absorb, Orsiro, Resolute Onyx, Synergy, and Xience Alpine stents. Following stent deployment at nominal pressure in ambient air, radial elastic recoil and foreshortening were measured. Flexibility (crimped and deployed stents) and longitudinal and radial resistances were evaluated using a mechanical tester.

Results

Biomechanical characteristics were significantly different for all tested devices (ANOVA, P < 0.01). The Synergy, Orsiro, and Xience Alpine stents presented the lowest elastic recoil. The Synergy and Resolute Onyx stents were the most flexible devices. The Xience Alpine and Absorb stents had the highest longitudinal and radial resistances.

Conclusions

Drug‐eluting coronary stents used in current clinical practice have very different biomechanical characteristics, which should be taken into consideration to select the most appropriate device for each clinical situation.
Right‐sided infective endocarditis in patients with uncorrected ventricular septal defect and patent ductus arteriosus: Two case reports
Authors: Sattwika Prenali Dwisthi , Hartopo Anggoro Budi , Anggrahini Dyah Wulan , Mumpuni Hasanah , Dinarti Lucia Kris
Published: September 2018

Key Clinical Message

Uncorrected left‐to‐right shunt congenital heart defect is a predisposing factor for infective endocarditis (IE), especially right‐sided IE which has different clinical manifestations and complications from left‐sided IE. Prompt diagnosis by means of transthoracic echocardiography and timely antibiotics management for IE are encouraged to prevent multiorgan failure and fatal pulmonary embolism.
Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis
Authors: Hino Keiko , Simó Sergi , Cooper Jonathan A.
Published: September 2018

Background: The E3 Cullin 5‐RING ubiquitin ligase (CRL5) is a multiprotein complex that has recently been highlighted as a major regulator of central nervous system development. Cullin 5 (Cul5) and the RING finger protein Rbx2 are two CRL5 core components required for CRL5 function in the brain, but their full expression patterns and developmental functions have not been described in detail. Results: Using a gene‐trap mouse model for Cul5 and a knock‐in–knockout mouse model for Rbx2, we show that lack of Cul5, but not Rbx2, disrupts blastocyst formation. However, Rbx2 is required for embryo survival at later embryonic stages. We also show that cul5 is expressed in the embryo proper as early as E7.5 and its expression is mostly restricted to the central nervous system and limbs at later time points. Finally, we show that rbx2 and cul5 are co‐expressed in most areas of the brain during development and in the adult. Conclusions: Our results show that Cul5, but not Rbx2, is required during early embryogenesis and suggests that Cul5 has Rbx2‐independent functions in early development. In the brain, Cul5 and Rbx2 are expressed in a similar fashion, allowing the nucleation of an active CRL5 complex. Developmental Dynamics 247:1227–1236, 2018. © 2018 Wiley Periodicals, Inc.
Interactions between two parasites of brown trout (Salmo trutta): Consequences of preinfection
Authors: Gopko Mikhail , Chowdhury M. Motiur R. , Taskinen Jouni
Published: September 2018

Preinfection by one parasitic species may facilitate or by contrast hamper the subsequent penetration and/or establishment of other parasites in a host. The biology of interacting species, timing of preinfection, and dosage of subsequent parasite exposure are likely important variables in this multiparasite dynamic infection process. The increased vulnerability to subsequent infection can be an important and often overlooked factor influencing parasite virulence. We investigated how the preinfection by freshwater pearl mussel Margaritifera margaritifera glochidia could influence the success of subsequent infection by the common trematode Diplostomum pseudospathaceum in brown trout Salmo trutta and vice versa whether preinfection by the trematode made fish more susceptible to glochidia infection. The first experiment was repeated twice with different (low and high) exposure doses to initiate the subsequent trematode infection, while in the second experiment we varied the timing of the preinfection with trematodes. The preinfection with glochidia made fish more vulnerable to subsequent infection with trematodes. Since the trematodes penetrate through the gills, we suggest that increased host vulnerability was most likely the result of increased respiration caused by the freshwater pearl mussel glochidia encysted on gills. In turn, brown trout preinfected with trematodes were more vulnerable to the subsequent glochidial infection, but only if they were preinfected shortly before the subsequent infection (20 hr). Fish preinfected with trematodes earlier (2 weeks before the subsequent infection) did not differ in their vulnerability to glochidia. These effects were observed at moderate intensities of infections similar to those that occur in nature. Our study demonstrates how the timing and sequence of exposure to parasitic species can influence infection success in a host–multiparasite system. It indicates that the negative influence of glochidia on host fitness is likely to be underestimated and that this should be taken into consideration when organizing freshwater pearl mussel restoration procedures.
Identification and functional analysis of spermatogenesis‐associated gene modules in azoospermia by weighted gene coexpression network analysis
Authors: Zheng Wenzhong , Zou Zihao , Lin Shouren , Chen Xiang , Wang Feixiang , Li Xianxin , Dai Jican
Published: September 2018

Nonobstructive azoospermia (NOA) or testicular failure is the most severe form of male infertility. A variety of conditions, both acquired and congenital, can cause azoospermia. However, in a large number of azoospermia patients who are classified as idiopathic cases, the etiology remains poorly understand mainly due to the lack of knowledge of all the genetic causes and molecular mechanisms responsible for spermatogenesis failure. Identification of the key gene modules and pathways‐related spermatogenesis failure might help to reveal the mechanisms of idiopathic azoospermia. Therefore, the expression patterns of spermatogenesis‐associated genes in NOA were analyzed by weighted gene coexpression network analysis (WGCNA) based on two public microarray data sets (GSE45885 and GSE45887), which included 51 samples and 32,321 genes. We identified a module (turquoise) that was significantly related to the Johnsen score of the testicular samples. In addition, the results of function and pathway enrichment analyses based on the online bioinformatics database Metascape revealed that genes in the turquoise module were mainly related to the process of spermatogenesis and spermatid development. To further identify spermatogenesis‐associated genes, a microarray data set (GSE926) of murine testis at different developmental time points was analyzed by WGCNA. The blue module in GSE926 was significantly related to the time of murine testis development. The overlap study and k‐core analysis based on protein–protein interaction network revealed that spermatogenesis‐ and spermatid development–associated genes, including glyceraldehyde‐3‐phosphate dehydrogenase, ADAM metallopeptidase domain 2, transition protein 1, testis‐specific serine kinase 2, transition protein 2, and germ cell‐associated 1 (GSG1), were further identified in the selected modules. The expression profile of GSG1 in human testis was chosen for further study using immunochemistry staining. Taken together, these screened gene modules and pathways provided a more detailed genetic and molecular mechanism underlying spermatogenesis failure occurrence and holds promise as potential diagnosis biomarkers and therapeutic targets.
Inclusion complexes of cysteinyl β‐cyclodextrin with baicalein restore collagen synthesis in fibroblast cells following ultraviolet exposure
Authors: Lee Joomin , Ahn Eunsook , Kim Seon‐Y. , Shin Yujeong , Ahn Seunghyun , Sung Jiha , Kim Hwanhee , Cho Eunae , Jung Seunho , Park Seyeon
Published: September 2018

Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl β‐cyclodextrin (β‐CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl β‐CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV‐exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized β‐CDs were found to promote baicalein‐induced collagen synthesis. Inclusion complexes of cysteinyl β‐CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl β‐CDs with baicalein also downregulated matrix metalloproteinase ‐1 and ‐3, and α‐smooth muscle actin expression. In addition, inclusion complexes of cysteinyl β‐CDs with baicalein attenuated the expression of caveolin‐1, but this treatment enhanced the UV‐induced phosphorylation of Smad in the transforming growth factor‐β pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.
Effects of cigarette smoke condensate on proliferation and pluripotency gene expression in mouse embryonic stem cells
Authors: Assadollahi Vahideh , Mohammadi Ebrahim , Fathi Fardin , hassanzadeh Kambiz , Erfan Mohamad Bager Khadem , Soleimani Farzad , Banafshi Omid , Yousefi Fayegh , Allahvaisi Ozra
Published: September 2018

Background

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocysts. They can be used as valuable experimental models to test the effects of drugs, chemicals, and environmental contaminants such as cigarette smoke condensate (CSC) on preimplantation embryo development. The aim of this study was to evaluate the effect of CSC on ESCs derived from mice with different genetic backgrounds and maternal ages.

Methods

The study groups consisted of mouse ESCs (mESCs) obtained from three sources: blastocysts developed from fertilized oocytes of two‐month‐old (2‐C57) and six‐month‐old (6‐C57) C57BL/6 inbred mice and those developed from fertilized oocytes of two‐month‐old (2‐NMRI) NMRI outbred mice. The groups of mESCs were exposed to 0.04, 4, and 40 μg/mL CSC. After exposure, we measured cell viability by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay and real‐time polymerase chain reaction for changes in expressions of
Oct4, Sox2, Nanog, Ahr, Bax, Bcl2, TFAM, and
POLG. The cell doubling time (DT) of these populations was also determined.

Results

We observed that CSC changed proliferation and DT in the 2‐C57 and 6‐C57 cells. There was no change in 2‐NMRI cells. Exposure to CSC caused changes in the gene expressions and induced apoptosis in all three cell lines.

Conclusion

Based on the results of the study, it can be concluded that CSC has an effect on the viability, DT and gene expression patterns in mouse ESCs and its effects vary based on the genetic background and maternal age of isolated mouse ESCs.
Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high‐throughput sequencing
Authors: Qiu Xiaoxia , Ke Xu , Ma Huaci , Han Liang , Chen Qingwen , Zhang Shu , Da Peng , Wu Hao
Published: September 2018

Circular RNAs (circRNA) are special noncoding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs (miRNA). They can regulate target gene messenger RNA expression and play important roles in many biological processes. However, expression profile and function of circRNAs in human tongue squamous cell carcinoma (TSCC) have not been reported. High‐throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues. A separate set (n = 20) of human TSCCs and corresponding adjacent tissues were subjected to reverse‐transcription polymerase chain reaction (RT‐PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA‐miRNA network analysis were also performed to predict the function of circRNA in TSCC. A total of 12 156 circRNAs were identified and annotated, most of the circRNAs were novel (
n = 6231) and exonic (62.09%). Statistical analysis revealed 322 differentially expressed (DE) circRNAs. RT‐PCR results showed that circRNA expression in TSCC was higher than that in adjacent tissues. GO functional analysis, KEGG pathway analysis, and circRNA‐miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain extent. The current study is the first to systematically characterize and annotate circRNA expression in TSCC, the majority were novel circRNAs. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor‐relevant miRNAs, indicating that circRNAs might be promoted development and progression of TSCC.
Role of high‐mobility group B1 in myocardial injury induced by coronary microembolization in rats
Authors: Chen Quan‐Fang , Wang Wei , Huang Zhou , Huang Dong‐Ling , Wang Fan , Li Jun , Liu Xue‐Feng , Sun Zhong‐Yi , Zeng Xiang‐Tao
Published: September 2018

Objective

This study aimed to explore the effects of high‐mobility group B1 (HMGB1) on coronary microembolization (CME)‐induced myocardial inflammation, myocardial apoptosis, and cardiac function injury in rats.

Methods

Forty Sprague‐Dawley rats were divided into sham operation group (sham group), microembolization group (CME group), CME + HMGB1 siRNA (HMGB1 siRNA) group, and CME + scrambled siRNA (control siRNA) group (10 rats in each group). The CME model group was constructed by injecting microembolism spheres into the apex of the left ventricle after clamping the ascending aorta. The sham group was constructed by injecting the same amount of saline. The HMGB1 siRNA group was injected with HMGB1 siRNA transfection complex via the tail vein 72 hours before CME modeling. The control siRNA group was injected with the same amount of scrambled siRNA mixture through the tail vein 72 hours before CME modeling. The cardiac function, serum cardiac troponin I level, and apoptotic index were examined 12 hours after the surgery. The levels of HMGB1, nuclear factor‐κB (NF‐κB) p65, glucose‐regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase‐12, cleaved caspase‐3, tumor necrosis factor‐α (TNF‐α), and interleukin 1β (IL‐1β) were detected.

Results

Myocardial dysfunction, enhanced serum cardiac troponin I level, and apoptotic index were induced following CME. Moreover, CME increased the expression of HMGB1, NF‐κB p65, GRP78, CHOP, cleaved caspase‐12, cleaved caspase‐3, TNF‐α, and IL‐1β. HMGB1 siRNA reversed these effects, whereas scrambled siRNA had no effect.

Conclusions

Inhibition of HMGB1 expression reduced CME‐induced myocardial injury and improved cardiac function. Hence, it may serve as a new target for preventing and treating the CME‐induced myocardial injury.
Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis
Authors: Zhang Xiaohui , Sun Renhua , Liu Liping
Published: September 2018

Objective

This study aimed to identify more potentially critical genes associated with atherosclerotic coronary artery disease (CAD).

Materials and Methods

Gene expression profile of GSE12288 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened in atherosclerotic CAD samples compared with controls, followed by weighed gene coexpression network analysis (WGCNA) by which the most significant module was identified. Gene coexpression network was constructed based on genes in the most significant module, and functional annotation was also performed. In addition, microRNAs (miRNAs) that were directly associated with CAD were screened from the literature, and the miRNA‐target regulatory network was constructed based on genes in the most significant module, followed by Gene Ontology (GO) and pathway enrichment analysis. Furthermore, we used another data set of GSE42148 from the GEO database to perform data validation.

Results

WGCNA analysis showed that the turquoise module may have the most important role in atherosclerotic CAD. Genes in this module were involved in translational elongation and intracellular signal transduction. Besides, we identified five confirmed CAD‐related miRNAs. TNPO1, RAP1B, and ZDHHC17 could be targeted by four of these miRNAs. Genes such as PPM1B could be regulated by three miRNAs. Moreover, TNPO1 and ZDHHC17 were involved in the GO terms associated with protein localization and transport and the immune system; RAP1B and PPM1B were linked with intracellular signal transduction‐related pathways. In addition, PPM1B and ZDHHC17 had accordantly significant expression changes in another data set GSE42148.

Conclusion

TNPO1, RAP1B, ZDHHC17, and PPM1B may play essential roles in the progression of coronary atherosclerosis.
Intestinal barrier tightening by a cell‐penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis
Authors: Thomas Sunil , Hoxha Kevther , Alexander Walker , Gilligan John , Dilbarova Rima , Whittaker Kelly , Kossenkov Andrew , Prendergast George C. , Mullin James M.
Published: September 2018

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell‐penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14C‐mannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.
In utero exposure to PM2.5 during gestation caused adult cardiac hypertrophy through histone acetylation modification
Authors: Wu Xiaoqi , Pan Bo , Liu Lingjuan , Zhao Weian , Zhu Jing , Huang Xupei , Tian Jie
Published: September 2018

Ambient particles with a diameter of <2.5 μm (PM2.5) is a global health concern, and exposure to PM2.5 contributes to the progression of cardiovascular morbidity and mortality. In this study, pregnant c57 mice were exposed to PM2.5 during the whole gestation (approximately 300 µg/m
3 PM2.5 for 2 hours/d). A significantly low birth weight was found after in utero PM2.5 exposure, and low body weight continued for 12 weeks after birth. In the offspring, remarkable destructions of cardiac ultrastructures were determined both in newborn and adult hearts. In adulthood, hearts of mice in the PM2.5 exposed group showed cardiac hypertrophy. Protein levels of p300, CBP (histone acetyltransferase), and acetylated histone3 lysine 9 (H3K9ac) increased in the trial group; messenger RNA (mRNA) levels of GATA binding protein 4 (GATA4) and myocyte enhancer factor 2C (Mef2c) (prohypertrophic transcription factors), and mRNA levels of the classic hypertrophic genes, such as α‐MHC and β‐MHC, increased significantly in the hearts of the PM2.5 exposed group. H3K9ac levels near the promoter region of GATA4 and Mef2c went up in the PM2.5 group. The binding affinities of p300/CBP with promoters of GATA4 and Mef2c increased notably. Taken together, out data indicated that maternal exposure to PM2.5 during gestation may cause a series of cardiovascular events in the offspring; histone acetylation modification may play an important role in the programming of cardiac hypertrophy.
Novel leptin receptor signaling mutants identify location and sex‐dependent modulation of bone density, adiposity, and growth
Authors: McCabe Ian C. , Fedorko Alyssa , Myers Martin G. , Leinninger Gina , Scheller Erica , McCabe Laura R.
Published: September 2018

Leptin, a hormone primarily produced by adipocytes, contributes to the regulation of bone health by modulating bone density, growth and adiposity. Upon leptin binding, multiple sites of the long form of the leptin receptor (LepRb) are phosphorylated to trigger activation of downstream signaling pathways. To address the role of LepRb‐signaling pathways in bone health, we compared the effects of three LepRb mutations on bone density, adiposity, and growth in male and female mice. The ∆65 mutation, which lacks the known tyrosine phosphorylation sites, caused obesity and the most dramatic bone phenotype marked by excessive bone adiposity, osteoporosis, and decreased growth, consistent with the phenotype of db/db and ob/ob mice that fully lack leptin receptor signaling. Mutation of LepRb Tyr
1138, which results in an inability to recruit and phosphorylate signal transducer and activator of transcription 3, also caused obesity, but bone loss and adiposity were more dominant in male mice and no growth defect was observed. In contrast, mutation of LepRb Tyr
985, which blocks SHP2/SOCS3 recruitment to LepRb and contributes to leptin hypersensitivity, promoted increased femur bone density only in male mice, while marrow adiposity and bone growth were not affected. Additional analyses of vertebral trabecular bone volume indicate that only the Tyr
1138 mutant mice exhibit bone loss in vertebrae. Together, our findings suggest that the phosphorylation status of specific sites of the LepRb contribute to the sex‐ and location‐dependent bone responses to leptin. Unraveling the mechanisms by which leptin responses are sex‐ and location‐dependent can contribute to the development of uniquely targeted osteoporosis therapies.
Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis
Authors: Hu Xin , Liang Yuanyuan , Zhao Bo , Wang Yongyi
Published: September 2018

Oxidative stress in retinal pigment epithelium (RPE) cells may contribute to the progression of age‐related macular degeneration. Thymoquinone (TQ), an active component derived from Nigella sativa, possesses antioxidative effect. However, the role of TQ in RPE cells under oxidative stress condition remains unclear. The present study aimed to examine the protective effect of TQ against hydrogen peroxide (H2O2)‐induced oxidative stress in human RPE cells. Our results showed that TQ improved the cell viability and apoptosis in H2O2‐induced ARPE cells. We also found that the levels of reactive oxygen species and malondialdehyde induced by H2O2 were reduced after the pretreatment of TQ. In addition, the inhibitory effect of H2O2 on the glutathione (GSH) level and superoxide dismutase activity was markedly attenuated by TQ pretreatment. Moreover, TQ enhanced the activation of Nrf2/heme oxygenase 1 (HO‐1) signaling pathway in H2O2‐induced ARPE cells. Knockdown of Nrf2 abolished the protective effect of TQ on H2O2‐induced oxidative damage. These results suggested that TQ protected ARPE cells from H2O2‐induced oxidative stress and apoptosis via the Nrf2/HO‐1 signaling pathway.
The molecular mechanisms of curcumin’s inhibitory effects on cancer stem cells
Authors: Zendehdel Elham , Abdollahi Elham , Momtazi‐Borojeni Amir Abbas , Korani Mitra , Alavizadeh Seyedeh Hoda , Sahebkar Amirhossein
Published: September 2018

Curcumin is a dietary polyphenol and a bioactive phytochemical that possesses anti‐inflammatory, antioxidant, anticancer, and chemopreventive properties, which make it capable of affecting multiple sites along the stem cell pathways to induce apoptosis in these cells. Curcumin’s function is through suppression of cytokine release, especially the secretion of interleukins. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types, leading to the development of tumors. Cancer stem cells (CSC) are capable of sustaining tumor formation and differentiation, and are normally characterized by self‐renewal mechanisms. Furthermore, these cells might be responsible for tumor relapse and resistance to therapy. Several studies have focused on the mechanisms of curcumin action in manipulating transcription factors, signaling pathways, CSC markers, microRNAs related to CSCs functions and apoptosis induction in various human cancer cells. In the present review, we aimed to summarize the reported molecular mechanisms of curcumin’s effects on CSCs.
Identification of potential mechanism and hub genes for neuropathic pain by expression‐based genome‐wide association study
Authors: Gu Yu , Qiu Zhuolin , Cheng Nan , Chen Chaojin , Hei Ziqing , Li Xiang
Published: September 2018

Neuropathic pain (NP) is a common pathological pain state with limited effective treatments. This study was designed to identify potential mechanisms and candidate genes using gene expression–based genome‐wide association study (eGWAS). All NP‐related microarray experiments were obtained from Gene Expression Omnibus and ArrayExpress. Significantly dysregulated genes were identified between experimental and untreated groups, and the number of microarray experiments in which each gene was dysregulated was calculated. Significantly dysregulated genes were ranked according to P values of the chi‐square test. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database, we performed functional and pathway enrichment analysis. Protein‐protein interaction (PPI) network and module analysis was performed using Cytoscape software. A total of 115 candidate genes were identified from 19 independent microarray experiments by eGWAS based on the Bonferroni threshold (
P < 2.97 × 10
−6). Immune and inflammatory responses, and complement and coagulation cascades, were respectively the most enriched biological process and pathways for candidate genes. The hub genes with highest connectivity in PPI network and two modules Ccl2 and Jun, and Ctss application of the eGWAS methodology can identify mechanisms and candidate genes associated with NP. Our results support the validity and prevalence of inflammatory and immune mechanisms across different NP models, and Ccl2, Jun, and Ctss may be the hub genes for NP.
Role of thrombin in the pathogenesis of atherosclerosis
Authors: Jaberi Najmeh , Soleimani Atena , Pashirzad Mehran , Abdeahad Hosein , Mohammadi Fariba , Khoshakhlagh Mahdieh , Khazaei Majid , Ferns Gordon A , Avan Amir , Hassanian Seyed Mahdi
Published: September 2018

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.
Novel finding of caveolin‐2 in apical membranes of proximal tubule and first detection of caveolin‐2 in urine: A promising biomarker of renal disease
Authors: Bulacio Romina Paula , Nosetto Evangelina Cecilia , Brandoni Anabel , Torres Adriana Mónica
Published: September 2018

Caveolin‐2 (Cav‐2) is expressed in a variety of cell tissue, and it has also been found in renal tissue. The expression of Cav‐2 in proximal tubules is still unclear. The aim of this study was to carry out a complete evaluation of the expression pattern of Cav‐2 in rat renal cortex to clarify and deepen the knowledge about the localization of Cav‐2 in the proximal tubules and also to evaluate its presence in urine. Male Wistar rats were used to assess Cav‐2 expression by Western blot analysis in homogenates, apical, and basolateral membranes from kidney cortex, in lysates and total plasma membranes from renal cortical cell suspensions, in urine, and in urinary exosomes. Cav‐2 was clearly expressed in renal cortex homogenates and in both apical and basolateral membranes isolated from kidney cortex, with a greater expression on the former membranes. It was also observed in lysates and in plasma membranes from cortical cell suspensions. Moreover, Cav‐2 was found in urine and in its exosomal fraction. These results confirmed the presence of Cav‐2 in proximal tubule cells in the kidney of healthy rats, and showed for the first time its expression at the apical membrane of these cells and in urine. Besides, urinary exosomal pathway could be involved in Cav‐2 urinary excretion under normal conditions. We observed an increase in the urinary abundance of Cav‐2 in two models of acute kidney injury, and thus we proposed the urinary excretion of Cav‐2 as a potential biomarker of kidney injury.
Roles for Kisspeptin in proliferation and differentiation of spermatogonial cells isolated from mice offspring when the cells are cocultured with somatic cells
Authors: Toolee Heidar , Rastegar Tayebeh , Solhjoo Somayeh , Mortezaee Keywan , Mohammadipour Mahshid , Kashani Iraj Regerdi , Akbari Mohammad
Published: September 2018

Kisspeptin (Kp) expression in testis has caused most of the recent research surveying its functional role in this organ. This peptide influences spermatogenesis and sperm capacitation, so it is considered as a regulator of reproduction. Kp roles exert through hypothalamic/pituitary/gonadal axis. We aimed to evaluate direct roles for Kp on proliferation and differentiation of spermatogonial cells (SCs) when the cells are cocultured with somatic cells. Somatic cells and SCs were isolated from adult azoospermic and newborn mice and then enriched using a differential attachment technique. After the evaluation of identity and colonization for SCs, the cells were cocultured with somatic cells, and three doses of Kp (10−8‐10−6 M) was assessed on proliferation (through evaluation of MVH and ID4 markers) and differentiation (via evaluation of c‐Kit and SCP3, TP1, TP2, and, Prm1 markers) of the coculture system. Investigations were continued for four succeeding weeks. At the end of each level of testosterone in the culture media was also evaluated. We found positive influence from Kp on proliferative and differentiative markers in SCs cocultured with somatic cells. These effects were dose‐dependent. There was no effect for Kp on testosterone level. From our findings, we simply conclude that Kp as a neuropeptide for influencing central part of reproductive axis could also positively affect peripheral processes related to spermatogenesis without having an effect on steroidogenesis.