bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of professional continuous glucose monitoring by clinical pharmacists in an ambulatory care setting
Authors: Van Dril Elizabeth , Schumacher Christie
Published: February 2019

Introduction

Use of continuous glucose monitoring (CGM) in the management of diabetes continues to grow. Despite professional‐use CGM serving as an opportunity for clinical pharmacists to improve care and generate revenue for managing patients with diabetes, there is limited literature describing their involvement with this technology.

Objectives

The primary objective was to determine if professional CGM improves measures of glycemic control including percentage of time in target glycemic range, change in estimated average interstitial glucose, and change in hemoglobin A1c (HbA1c) from baseline to postintervention. Secondary objectives were to evaluate revenue generation measured by reimbursement rates for Current Procedural Terminology (CPT) codes 95250 and 95251 and utilization of clinical pharmacist services related to professional CGM.

Methods

This was a quasi‐experimental, retrospective, pre‐post intervention analysis. Patients that had a professional CGM placed and more than 24 hours of data interpreted by a clinical pharmacist were included for analysis. All clinical data were extracted from patients' electronic medical records, while reimbursement data were provided by the organization's billing department.

Results

Twenty‐nine patients that received professional CGM were included for analysis. Patients' mean baseline and post‐intervention HbA1c were 9.0% and 8.3%, respectively (P = 0.156). There was no difference in the mean percentage of time in target glycemic range (P = 0.966) or mean estimated average interstitial glucose (P = 0.779) from baseline to post‐intervention. Patients met with clinical pharmacists for a total of 68 follow‐up visits during their individual 14‐day wear periods, 14 of which were unanticipated visits. The mean payment amount for CPT code 95250 was $126.87, while $39.17 was received for 95251.

Conclusions

Clinical pharmacist‐led professional CGM did not demonstrate a statistically significant difference in measures of glycemic control; however, the 14‐day device wear period provided opportunities for optimization of antihyperglycemic therapy that resulted in a clinically significant reduction in HbA1c and reimbursement for clinical pharmacy services.
Value of a clinical pharmacy on‐call program on postgraduate year one pharmacy residents
Authors: Coglianese Nicole M. , Jarrett Jennie B.
Published: February 2019

Introduction

On‐call programs are innovative learning opportunities within pharmacy residencies to assist residents in fostering critical thinking skills, communication skills, and clinical autonomy. The objective of this study is to determine the perceived educational and professional value of the University of Illinois at Chicago (UIC) on‐call program on postgraduate year one (PGY1) pharmacy residency alumni.

Methods

A prospective, cross‐sectional survey was conducted from 1 March 2018 to 1 April 2018 among pharmacy residency alumni who participated in the UIC pharmacy residency on‐call program between 2000 and 2017. The primary outcome of this study was to evaluate the perceptions of the value of the on‐call program from pharmacy residents relating to pharmacotherapeutic areas strengthened and professional skill development. The secondary outcomes of this study were to evaluate how pharmacy residents perceived the on‐call program to affect their interprofessional outcomes and utilization in their current professional role. Quantitative results were analyzed using descriptive statistics.

Results

Ninety‐five PGY1 pharmacy residency alumni responded to the electronic survey about the on‐call program; response rate of 58.6%. Overall, alumni reported a high satisfaction (93/94; 98.9%) and positive perception (93/94; 98.9%) of the on‐call program as a highly valuable component of the PGY1 residency program. PGY1 pharmacy residents reported participating in a variety of clinical practice activities across many specialties (infectious diseases, critical care, emergency medicine, and general medicine) while on call. Lastly, the on‐call program is a highly interprofessional experience allowing interactions with a variety of health care providers (physicians, nurses, pharmacists, and advanced practice providers).

Discussion

The UIC on‐call program provided an overall positive experience for PGY1 pharmacy residents that felt that the experience exposed them to a variety of pharmacotherapeutic knowledge areas and strengthened their clinical skills. Furthermore, the UIC on‐call program is perceived to be a highly interprofessional experience.
Schizandrin protects H9c2 cells against lipopolysaccharide‐induced injury by downregulating Smad3
Authors: Zhang Xuehua , Zhao Yanyan , Bai Dong , Yuan Xiutai , Cong Shan
Published: February 2019

Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti‐inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated with schizandrin alone or in combination with lipopolysaccharide (LPS), after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damage as cell viability was repressed and the apoptosis was induced. In the meantime, LPS promoted the release of proinflammatory cytokines including interleukin 1β (IL‐1β), IL‐8, IL‐6, and tumor necrosis factor (TNF‐α) while repressing the release of the anti‐inflammatory cytokine IL‐10. Schizandrin could promote H9c2 cell migration and long‐term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS‐induced cell loss and inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencing of Smad3 deactivated c‐Jun N‐terminal kinase (JNK) and nuclear factor κB (NF‐κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS‐induced injury in the H9c2 cells and promoted the recovery of myocardial tissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF‐κB pathways.
Changing expression profiles of mRNA, lncRNA, circRNA, and miRNA in lung tissue reveal the pathophysiological of bronchopulmonary dysplasia (BPD) in mouse model
Authors: Wang Juan , Yin Jing , Wang Xingyun , Liu Heng , Hu Yin , Yan Xiangyun , Zhuang Bin , Yu Zhangbin , Han Shuping
Published: February 2019

New perinatal care technologies have improved the survival rate of preterm neonates, but the prevalence of bronchopulmonary dysplasia (BPD), one of the most intractable problems in neonatal intensive care unit (NICU), remains unchanged. In present study, high‐throughput sequencing (HTS) was performed to detect the expression profiles of long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in hyperoxia‐induced BPD mouse model. Significant differentially expressed RNAs were selected and clustered between the BPD group and the control group. The results revealed that expressions of 1778 lncRNAs, 1240 mRNAs, 97 circRNAs, and 201 miRNAs were significantly altered in the BPD group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to predict the potential functions of differentially expressed RNAs. lncRNA‐mRNA and circRNA‐miRNA coexpression networks were constructed to detect their association with the pathogenesis of BPD. Our study provides a systematic perspective on the potential function of RNAs during BPD.
Inhibition of TREM‐1 attenuates inflammation and lipid accumulation in diet‐induced nonalcoholic fatty liver disease
Authors: Rao Shenzong , Huang Jingsong , Shen Zhijun , Xiang Changgang , Zhang Min , Lu Xueliang
Published: February 2019

In the liver tissues of obese diabetic or nondiabetic patients, triggering receptor expressed on myeloid cells‐1 (TREM‐1) is usually found to be upregulated, thus leading to upregulation of various inflammatory cytokines and lipid accumulation. On the other hand, nonalcoholic fatty liver disease (NAFLD), characterized by excess lipid accumulation, and inflammatory injury in liver, is becoming an epidemic disease, globally. In the present study, we aimed to investigate the biological role and the underlying mechanisms of TREM‐1 in NAFLD. upregulation of TREM‐1 occurred in high‐fat diet (HFD)‐induced mice NAFLD model and oleic acid‐treated HepG2 and primary mouse hepatocytes cell model at messenger RNA and protein levels. Functional studies established that overexpression of TREM‐1 displayed hyperlipidemia, and increased in inflammatory indicators and lipid accumulation‐related genes, which was ameliorated by knockdown of TREM‐1. Our results also showed that obvious lipid accumulation and inflammatory injury occurred in the liver tissue of HFD‐fed mice, while treatment with lentiviral vector short hairpin TREM showed marked improvement in tissue morphology and architecture and less lipid accumulation, thus deciphering the mechanism through which knockdown of TREM‐1 ameliorated the inflammatory response and lipid accumulation of NAFLD mice through inactivation of the nuclear factor‐κB (NF‐κB) and PI3K/AKT signal pathways, respectively. In conclusion, TREM‐1/NF‐κB and TREM‐1/PI3K/AKT axis could be an important mechanism in ameliorating the inflammatory response and lipid accumulation, respectively, thus shedding light on the development of novel therapeutics to the treatment of NAFLD.
Genetic association study of promoter variation rs3761549 in the FOXP3 gene of Iranian patients diagnosed with brain tumour
Authors: Moradi Mehdi , Naeimi Sirous , Asadzade Shekofeh , Rahi Azar
Published: February 2019

Forkhead box P3 (FOXP3) gene (Gene ID: 50943, Xp11.23) is an X‐linked gene that encodes FOXP3 protein, an essential transcription factor in CD4+ CD25+ FOXP3 regulatory T (Treg) cells. FOXP3 mutation has been linked with the pathogenesis of several tumours; however, little is known about the role of single‐nucleotide polymorphism (SNP) in its promoter region and its correlation with brain tumour. In the present study, we have investigated the association between SNPs in the promoter region of FOXP3 gene, a promoter SNP, −2383 C/T (rs3761549) with susceptibility to brain cancer in a population of Iran. The distribution of case, control, age and sex was balanced and with rs3761549 C/T allele frequencies distribution also falling in Hardy‐Weinberg equilibrium (P = 0.053 and 0.062). The allele C of rs3761549 is lower in the brain tumour cases when compared with the controls (364 vs 392, P = 0.005). The frequency of combined T variant genotype (TT + CT) was significantly higher in the brain cancer cases compared with the controls (28 vs 8, P = 0.001), which was consistent with the T allele distribution. When we used the CC genotype as a reference, we found that both CT and TT genotypes were associated with a higher risk of developing brain tumour (odds ratio [OR], 0.3583; 95% confidence interval [CI], 0.164‐0.8197 and OR, 0; 95% CI, 0‐0.4118, respectively).
Integration of metabolomic and transcriptomic profiles to identify biomarkers in serum of lung cancer
Authors: Sun Quan , Zhao Wei , Wang Lei , Guo Fei , Song Dongjian , Zhang Qian , Zhang Da , Fan Yingzhong , Wang Jiaxiang
Published: February 2019

We used blood serum samples collected from 31 lung cancer (LC) patients and 29 healthy volunteers in this study. Levels of serum metabolites were qualitative quantified with gas chromatography‐mass spectrometry (GC‐MS), and the data were analyzed by partial least‐squares discrimination analysis (PLS‐DA). Based on the Kyoto Encyclopedia of Genes and Genomes database, we performed pathway‐based analysis utilizing metabolites presented at differential abundance between the LC serum samples and the normal healthy serum samples for systematical investigation on the metabolic alterations associated with LC pathogenesis. Finally, we analyzed the significantly enriched pathways as well as their relevant differentially expressed messenger RNAs, and drawn a correlation network plot to identify the serum metabolic biomarkers and the significantly altered metabolic pathways for LC. GC‐MS analysis showed that 23 of the 169 metabolites identified were significantly different. PLS‐DA model revealed that 13 of these metabolites were with variable importance > 1, and particularly five were with area under curve > 0.9. Pathway‐based analysis demonstrated that five of eight enriched metabolic pathways were statistically significant with false discovery rate < 0.05. Lastly, the correlation networks between these pathways and their related genes suggested that 29 genes had correlation degree > 10, which were mainly engaged in the purine metabolism. In conclusion, we identified indole‐3‐lactate, erythritol, adenosine‐5‐phosphate, paracetamol and threitol as serum metabolic biomarkers for LC through metabolomics analysis. Besides, we identified the purine metabolism as the significantly altered metabolic pathway in LC with the help of transcriptomics analysis.
Association of PTPN1 polymorphisms with breast cancer risk: A case‐control study in Chinese females
Authors: Huang Shuya , Liu Liyuan , Xiang Yujuan , Wang Fei , Yu Lixiang , Zhou Fei , Cui Shude , Tian Fuguo , Fan Zhimin , Geng Cuizhi , Cao Xuchen , Yang Zhenlin , Wang Xiang , Liang Hong , Wang Shu , Jiang Hongchuan , Duan Xuening , Wang Haibo , Li Guolou , Wang Qitang , Zhang Jianguo , Jin Feng , Tang Jinhai , Li Liang , Zhu Shiguang , Zuo Wenshu , Ye Chunmiao , Zhou Wenzhong , Yin Gengshen , Ma Zhongbing , Yu Zhigang
Published: February 2019

Background

Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non‐receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk.

Methods

We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case‐control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist‐hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database.

Results

There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m
2, while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM.

Conclusion

Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.
Long noncoding RNA DLX6‐AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR‐424‐5p
Authors: Li Dan , Tang Xianbin , Li Man , Zheng Yi
Published: February 2019

Long noncoding RNAs (lncRNAs) played an important role in tumorigenesis and development of hepatocellular carcinoma (HCC). In this study, we first demonstrated that lncRNA DLX6 antisense RNA 1 (DLX6‐AS1) was upregulated in cancer tissues and cells lines compared with normal adjacent and cell line. Knock‐down DLX6‐AS1 by transfection with small interfering RNA (siRNA) suppressed cell proliferation, migration, and invasion of HCC cells. Cell cycle analysis showed that cells transfected with siRNA were arrested in G0/G1 phase. Then, we performed dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay to show that DLX6‐AS1 could bind with miR‐424‐5p. And cotransfection inhibitor of miR‐424‐5p with siRNA of DLX6‐AS1 could abolish the inhibitory effect of siRNA of DLX6‐AS1 on cell proliferation, migration, and invasion. Moreover, we further demonstrated that the oncogene WEE1 G2 checkpoint kinase (WEE1) was the target of miR‐424‐5p and expression levels of WEE1 were positive correlation with that of DLX6‐AS1. Taken together, these results suggested that upregulated DLX6‐AS1 promoted cell proliferation, migration, and invasion of HCC through increasing expression of WEE1 via targeting miR‐424‐5p.
The function of BED finger domain of Zbed3 in regulating lung cancer cell proliferation
Authors: Liu Haifeng , Shi Xiuying , Fan Xiaoxi , Zhang Di , Jiang Biying , Zhao Yang , Fan Chuifeng
Published: February 2019

Zbed3, a BED finger domain‐containing protein was found to promote cancer proliferation by regulating β‐catenin expression through interacting with Axin. But whether and how BED finger domain function in regulating cancer proliferation is unknown. We constructed five mutants of Zbed3, which lacks the Axin‐Zbed3 binding site, and the 43 to 52, 69 to 77, 87 to 92, and 97 to 104 sequences in BED finger domain, respectively and named them as Z‐A, Z1, Z2, Z3, and Z4. Transfection of both wild‐type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05), but not Z2 (P > 0.05) significantly upregulated β‐catenin expression in NCI‐H1299 cells. Overexpression of both wild‐type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05) but not Z2 (P > 0.05) significantly promoted cancer cell proliferation and invasion. The ability of proliferation (P < 0.05) but not invasion (P < 0.05) of cancer cells transfected with Z1 and Z4 was significantly lower than that with wild‐type Zbed3 and Z3. Overexpression of wild‐type Zbed3 (P < 0.05) but not the mutant Z‐A, which lacks the binding site with Axin and Z2 (P > 0.05) significantly upregulated the interaction of Axin and Zbed3, β‐catenin expression and the activity of Wnt signaling. Both overexpression of wild‐type Zbed3 and the mutant Z1 and Z4 significantly upregulated the activity of Wnt signaling and promoted cancer cell proliferation (P < 0.05) but only overexpression of wild‐type Zbed3 (P < 0.05), but not the mutant Z1, and Z4 (P > 0.05), significantly upregulated the expression of proliferating cell nuclear antigen (PCNA) in NCI‐H1299 cells. These results indicate that Zbed3 may promote lung cancer cell proliferation through regulating PCNA expression besides regulating β‐catenin expression and BED finger domain can impact on this function.
Theoretical study on photophysical properties of a series of functional pyrimidine‐based organic light‐emitting diodes emitters presenting thermally activated delayed fluorescence
Authors: Zhu Qiuling , Guo Xugeng , Zhang Jinglai
Published: February 2019

Issue concerning accurate prediction of the reverse intersystem crossing rate (kRISC) is critical for developing novel efficient thermally activated delayed fluorescence (TADF) materials. In this contribution, the kRISC rates from the lowest excited triplet T1 state to the lowest excited singlet S1 state were evaluated for five donor‐π‐acceptor‐type pyrimidine‐based TADF emitters using the semiclassical Marcus theory. Both the singlet‐triplet energy difference (ΔEST) and spin–orbit coupling (V) between the S1 and T1 states were investigated by performing the density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) calculations. In addition, their fluorescence emission wavelengths (λem) were also calculated at the TD‐DFT level. The predicted kRISC and λem values are found to reproduce well the available experimental findings. The present results reveal that the kRISC rates of molecules possessing the unsymmetrical diphenyl pyrimidine acceptor core are calculated to be slightly larger than those of their analogues with the symmetrical diphenyl pyrimidine. In addition, introducing two tert‐butyl groups into the 2,7‐positions of the donor moiety of the latter is also an effective method for increasing kRISC when designing TADF emitters. Such a difference is related to the nature of the T1 excited state. A more remarkable charge‐transfer (CT) contribution to the state can achieve a smaller ΔEST, leading to a more efficient RISC process, and consequently a shorter delayed fluorescence lifetime as observed experimentally. © 2019 Wiley Periodicals, Inc.
Influence of time of residence on the sense of community and satisfaction with life in immigrants in Spain: The moderating effects of sociodemographic characteristics
Authors: Millán‐Franco Mario , Gómez‐Jacinto Luis , Hombrados‐Mendieta Isabel , García‐Martín Miguel Angel , García‐Cid Alba
Published: February 2019

Migration is an example of adaptation with enduring effects over time and in different cultures. Few studies have analyzed the effect of the sense of community (SOC) on satisfaction with life (SWL) over time while taking into account the moderating effects of sociodemographic characteristics. We propose a model that explains the influence of time of residence on the SOC and SWL. It was hypothesized that the SOC has a positive influence on SWL and that SWL is moderated by sociodemographic characteristics and cultural differences. Participants were 2,211 immigrants residing in Malaga (Spain). Results show a positive association between years of residence and the SOC and the SWL. A positive association was found between the SOC and SWL. This study shows the relevance of analyzing the moderating effects of sociodemographic characteristics in different immigrant groups rather than according to the migration process as a whole to develop specific intervention strategies.
Wnt1‐inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway
Authors: Wang Liang , Sun Jin , Gao Pei , Su Ke , Wu Huanhuan , Li Junli , Lou Weihua
Published: February 2019

Wnt1‐inducible signaling protein 1 (WISP1) is a matricellular protein and downstream target of Wnt/β‐catenin signaling. This study sought to determine the role of WISP1 in glucose metabolism and chemoresistance in laryngeal squamous cell carcinoma. WISP1 expression was silenced or upregulated in Hep‐2 cells by the transfection of WISP1 siRNA or AdWISP1 vector. Ectopic WISP1 expression regulated glucose uptake and lactate production in Hep‐2 cells. Subsequently, the expression of glucose transporter 1 (GLUT1) was significantly modulated by WISP1. Furthermore, WISP1 increased cell survival rates, diminished cell death rates, and suppressed ataxia‐telangiectasia‐mutated (ATM)‐mediated DNA damage response pathway in cancer cells treated with cisplatin through GLUT1. WISP1 also promoted cancer cell tumorigenicity and growth in mice implanted with Hep‐2 cells. Additionally, WISP1 activated the YAP1/TEAD1 pathway that consequently contributed to the regulation of GLUT1 expression. In summary, WISP1 regulated glucose metabolism and cisplatin resistance in laryngeal cancer by regulating GLUT1 expression. WISP1 may be used as a potential therapeutic target for laryngeal cancer.
RETRACTED: Silencing lncRNA PVT1 inhibits activation of astrocytes and increases BDNF expression in hippocampus tissues of rats with epilepsy by downregulating the Wnt signaling pathway
Authors: Zhao Teng , Ding Ying , Li Min , Zhou Chunkui , Lin Weihong
Published: February 2019

The aim of this study is to investigate the effects of long‐chain noncoding RNA plasmacytoma variant translocation 1 (PVT1) on the activation of astrocytes and the expression of brain‐derived neurotrophic factor (BDNF) in hippocampus tissues of epileptic rats. The epilepsy rat model was induced by intraperitoneal injection of lithium chloride–pilocarpine. Successfully modeled rats were grouped, and their spatial learning and memory, neuronal loss, number of TdT‐mediated dUTP nick labeling (TUNEL)‐positive cells, and the expression of cleaved‐caspase‐3, pro‐caspase‐3, Bax, Bcl‐2, GFAP, BDNF, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), IL‐6, axin, and cyclin D1 in hippocampus tissues were evaluated. Increased expression of PVT1 was found in hippocampus tissues of epileptic rats. Silencing of PVT1 improved spatial learning and memory, decreased neuronal loss, decreased the number of TUNEL‐positive cell, decreased the expression of cleaved‐caspase‐3 and Bax while increased pro‐caspase‐3 and Bcl‐2 expression, decreased the expression of GFAP, increased the expression of BDNF, decreased the expression of TNF‐α, IL‐1β, and IL‐6, and decreased the expression of axin and cyclin D1 in hippocampus tissues in epileptic rats. Our study provides evidence that the inhibition of PVT1 may decrease the loss of neurons, inhibit the activation of astrocytes, and increase the expression of BDNF in hippocampus by downregulating the Wnt signaling pathway.
MicroRNA‐449b‐5p targets HMGB1 to attenuate hepatocyte injury in liver ischemia and reperfusion
Authors: Zhang Yong , Lv Jianrui , Wu Gang , Li Wei , Zhang Zhenni , Li Weisong , Lei Xiaoming
Published: February 2019

MicroRNAs (miRNAs) participate in the pathological process of liver ischemia/reperfusion (I/R) injury. MiR‐449b‐5p is the target miRNA of high mobility group box 1 (HMGB1). Its role and molecular mechanism in liver I/R injury remain unidentified. In this study, we found a protective effect of miR‐449b‐5p against hepatic I/R injury. HMGB1 expression significantly increased, whereas miR‐449b‐5p dramatically decreased in patients after liver transplant and in L02 cells exposed to hypoxia/reoxygenation (H/R). A dual‐luciferase reporter assay confirmed the direct interaction between miR‐449b‐5p and the 3′ untranslated region of HMGB1 messenger RNA. We also found that overexpression of miR‐449b‐5p significantly promoted cell viability and inhibited cell apoptosis of L02 cells exposed to H/R. Moreover, miR‐449b‐5p repressed HMGB1 protein expression and nuclear factor‐κB (NF‐κB) pathway activation in these L02 cells. In an in vivo rat model of hepatic I/R injury, overexpression of miR‐449b‐5p significantly decreased alanine aminotransferase and aspartate aminotransferase and inhibited the HMGB1/NF‐κB pathway. Our study thus suggests that miR‐449b‐5p alleviated hepatic I/R injury by targeting HMGB1 and deactivating the NF‐κB pathway, which may provide a novel and promising therapeutic target for hepatic I/R injury.
KIF20B promotes the progression of clear cell renal cell carcinoma by stimulating cell proliferation
Authors: Li Gang , Xie Zun‐Ke , Zhu Dong‐Sheng , Guo Tao , Cai Qi‐Liang , Wang Yi
Published: February 2019

Renal cell carcinoma (RCC) is a common urinary system cancer with high morbidity and mortality rate. Clear cell renal cell carcinoma (ccRCC) is a highly aggressive and common type of RCC. More and effective therapeutic targets are badly needed for the treatment of ccRCC. Kinesin family protein (KIF)20B, also named M‐phase phosphoprotein 1, was reported as a microtubule‐associated, plus‐end‐directed kinesin. KIF20B was involved in multiple cellular processes such as cytokinesis. Multiple studies indicated the oncogenic role for KIF20B in several types of tumors, including breast cancer and bladder cancer. However, the possible role of KIF20B in the progression of renal carcinoma is still unknown. Herein, our study demonstrated that KIF20B was relatively highly expressed in ccRCC tissues. In addition, KIF20B was inversely related to the clinical features including tumor size and T stage. We further found that inhibition of the KIF20B expression by a specific short hairpin RNA obviously reduces proliferation of ccRCC cells both in vitro and in vivo. Our study reveals the involvement of KIF20B in ccRCC progression. Generally, KIF20B is a promising novel therapeutic for the treatment of clear cell RCC.
Human CD8+CD25+CD127low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression
Authors: Rouas Redouane , Merimi Makram , Najar Mehdi , El Zein Nabil , Fayyad‐Kazan Mohammad , Berehab Mimoune , Agha Douaa , Bron Dominique , Burny Arsene , Rachidi Walid , Badran Bassam , Lewalle Philippe , Fayyad‐Kazan Hussein
Published: February 2019

Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune‐related genes and their immunomodulatory properties have been associated with different immune‐based diseases. The miRNA signature of human peripheral blood (PB) CD8+CD25
+CD127
low Tregs has not been described yet. We thus identified, using TaqMan low‐density array (TLDA) technique followed by individual quantitative real‐time polymerase chain reaction (qRT‐PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8
+CD25
+CD127
low Tregs in comparison to CD8
+CD25
− T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′‐untranslated region (3′‐UTR) of key Treg cell‐immunomodulatory genes with a special focus on interleukin 10 (IL‐10) and transforming growth factor β (TGF‐β). Having identified potential miR target sites in the 3′‐UTR of IL‐10 (miR‐27b‐3p and miR‐340‐5p) and TGF‐β (miR‐330‐3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR‐27b‐3p and miR‐340‐5p, downregulated IL‐10 expression upon targeting its 3′‐UTR. Similarly, overexpression of miR‐330‐3p negatively regulated TGF‐β expression. These results highlighted an important impact of the CD8
+ Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer.
Wingless‐type inducible signaling pathway protein‐1 (WISP1) adipokine and glucose homeostasis
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein
Published: February 2019

Whilst the growing global prevalence of diabetes mellitus is a major healthcare problem, the exact pathophysiology of insulin resistance leading to diabetes mellitus remains unclear. Studies have confirmed that increased adiposity is linked to lower insulin sensitivity through the expression and release of adipocyte‐derived proteins such as adipokines. Wingless‐type (Wnt) inducible signaling pathway protein‐1 (WISP1) is a newly identified adipokine that has important roles in many molecular pathways and cellular events, with the suggestion that WISP1 adipokine is closely correlated to the progression of insulin resistance. Studies have shown that circulatory levels of WISP adipokine are higher in obese patients accompanied with increased insulin resistance. However, the exact role of WISP1 adipokine in the induction of insulin resistance is not completely understood. In this review, we detail the latest evidence showing that the WIPS1 adipokine impairs glucose homeostasis and induces diabetes mellitus.
Learning from small numbers: Studying ruling relations that gender and race the structure of U.S. engineering education
Authors: Pawley Alice L.
Published: February 2019

Background

Women and men of color and White women participate in American engineering education in lower proportions than they represent in the general U.S. population. Much existing engineering education research uses individual‐level (such as psychological) theories to explain this difference. The study reported here instead takes a structural perspective, asking how social relations are coordinated in engineering education.

Purpose

This study explores how the intersection of ruling relations, critical race, and feminist theories can investigate how gender and race are built into engineering education's institutional structure.

Design/Method

This study used interviews collected from 17 women and men of color and White women who were engineering undergraduate students at U.S. universities. The interviews were drawn from a project that takes as its premise that learning from such small numbers of students facilitates analyzing data intersectionally. The primary analysis used narrative methods through repeated readings.

Results

I offer empirically based illustrations of ruling relations in U.S. universities and schools of engineering that unduly impact minoritized populations. These illustrations include discussions of financial aid knowledge, meeting the needs of transfer and Native students, and how schools crafting “the ideal student” as a young, single White male problematically impact minoritized students. The results illustrate how ruling relations structure engineering education in White‐ and male‐dominated ways.

Conclusions

This paper offers questions to help readers consider how ruling relations race and gender their own institutions. In addition, it offers an interpretive, emergent method for interrogating institutional structure and ideas for future work using ruling relations in engineering education research.
Implication of palynological techniques for the authentication of adulterated drugs traded with the same name in different herbal markets of district Lahore, Pakistan
Authors: Ramzan Sehrish , Shaheen Shabnum , Hussain Khadim , Sharifi‐Rad Javad , Khan Muhammad Asaf , Harun Nidaa , Jaffer Mehwish , Khan Farah
Published: February 2019

Adulteration in traded medicinal plants is a significant issue nowadays and use of these adulterated medicinal plants can impose harmful impact to end user. However, this problem can be overcome by ensuring the identification of traded medicinal plants which are used in making different herbal medicines. In this regard, palynological markers are considered to be an important taxonomic tool in the identification of original medicinal plant from its adulterant. Hence this study attempted to provide particular reliable palynological markers for distinguishing selected medicinal plants from their adulterants, that is, Cinnamomum verum versus Canella winterana, Cinnamomum tamala versus Cinnamomum obtusifolium, Gymnema sylvestre versus Gymnema lactiferum, Artemisia maritima versus Artemisia absinthium, Achillea millefolium versus Adhatoda vasaka, Sphaeranthus indicus versus Sphaeranthus africanus, Averrhoa carambola versus Butea monosperma, and Morus nigra versus Morus alba. Results demonstrated great variations in multiple palynological characters between original medicinal plant and its adulterant such as in pollen size, shape, colpi length, exine, intine thickness, and fertility. In equatorial view, circular to spheroidal shape of pollen was found in A. millefolium while oblate shape was observed in A. vasaka. Similarly B. monosperma pollen was 34 μm, whereas pollen of its adulterant A. carambola was 21 μm. Moreover, colpi length of A. maritima was 11.8 μm, whereas 4.5 μm in A. absinthium. Hence it can be concluded that palynological characters are commendably helpful in identification of genuine medicinal plant from its adulterant.
Genetic counseling supervisor strategies: An elaboration of the Reciprocal‐Engagement Model of Supervision
Authors: Suguitan Mike Darren , McCarthy Veach Patricia , LeRoy Bonnie , Wherley Colleen , Redlinger‐Grosse Krista
Published: February 2019

Clinical supervision plays a key role in the training of genetic counselor practitioners. The Reciprocal‐Engagement Model of Supervision (REM‐S) is a recently published model of genetic counseling supervision centered on the supervisor–student relationship. The REM‐S comprises five tenets and 16 goals that reciprocally interact to achieve three broad supervision outcomes. Lacking, however, is a comprehensive set of supervisor strategies that correspond to the tenets and goals. This study aimed to elaborate the REM‐S by identifying strategies genetic counselor supervisors use to accomplish each REM‐S goal when they supervise students in clinical rotations. Nineteen prenatal, pediatric, and cancer genetic counselor supervisors from clinics in a major Midwestern city participated in one of three focus groups. Eleven semistructured questions were asked about strategies they use when attempting to accomplish each REM‐S goal. Directed content analysis yielded a total of 14 different strategy domains that vary in their frequency for accomplishing each REM‐S goal. Participants identified between nine and 13 strategy domains for each goal. Across all REM‐S goals, the most frequent strategy domains are: Assess student; Practice self‐reflection to increase supervisor self‐awareness; and Establish student goals and expectations. The present findings elaborate the REM‐S by identifying supervisor strategies corresponding to the REM‐S goals. These strategies can inform training in clinical supervision, and they can be the focus of observational studies designed to identify supervisor behaviors that characterize each strategy.
Immunoglobulin G4‐related disease mimicking gallbladder cancer with associated choledochal cyst: A case report of a malignant masquerade
Authors: Kulkarni Aditya A , Soni Praveen , Sharma Vipan K , Bal Amanjit , Rana Surinder S , Gupta Rajesh
Published: February 2019

Immunoglobulin G4 (IgG4)‐related disease is a recently described autoimmune disease that can involve diverse organ systems, causing pancreatitis, cholangitis, retroperitoneal fibrosis, and thyroiditis to name a few. Key histological features include storiform fibrosis, obliterative venulitis, and intense inflammatory infiltrate composed of lymphoplasmacytic cells. The disease has a tendency to present with mass‐forming lesions, often difficult to differentiate from malignant processes. We report the case of a 48‐year‐old male from an area endemic for gallbladder cancer (north India). He presented with a short history of abdominal pain and was found to have asymmetric thickening of the gallbladder wall with a soft‐tissue mass invading the adjacent liver. In addition, the bile duct was dilated throughout its extent. A clinical and radiological diagnosis of gallbladder cancer with choledochal cyst was made, and the patient underwent radical cholecystectomy with bile duct excision. Histopathology surprisingly demonstrated IgG4‐related disease with no evidence of malignancy. Notably, serum levels of immunoglobulins were found to be normal. Preoperative diagnosis was challenging due to the absence of other manifestations. IgG4‐related disease is a possible diagnostic pitfall and should be included as a possible differential diagnosis for gallbladder masses.
Coverability of graph by three odd subgraphs
Authors: Petruševski Mirko , Škrekovski Riste
Published: February 2019

An odd graph is a graph whose vertex degrees are all odd. As introduced by Pyber in 1991, an odd edge‐covering of graph is a family of odd subgraphs that cover its edges. The minimum size of such family is denoted by . Answering a question raised by Pyber, Mátrai proved in 2006 that for every simple graph . In this study, we characterize the same inequality for the class of loopless graphs by proving that, apart from four particular types of loopless graphs on three vertices, every other connected loopless graph admits an odd 3‐edge‐covering. Moreover, there exists such an edge‐covering with at most two edges belonging to more than one subgraph and no edge to all three subgraphs. The latter part of this result implies an interesting consequence for the related notion of odd 3‐edge‐colorability. Our characterization presents a parity counterpart to the characterization of Matthews from 1978 concerning coverability of graph by three even subgraphs.
The influence of age‐associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV
Authors: Ahn Mi Young , Jiamsakul Awachana , Khusuwan Suwimon , Khol Vohith , Pham Thuy T , Chaiwarith Romanee , Avihingsanon Anchalee , Kumarasamy Nagalingeswaran , Wong Wing Wei , Kiertiburanakul Sasisopin , Pujari Sanjay , Nguyen Kinh V , Lee Man Po , Kamarulzaman Adeeba , Zhang Fujie , Ditangco Rossana , Merati Tuti P , Yunihastuti Evy , Ng Oon Tek , Sim Benedict L H , Tanuma Junko , Ratanasuwan Winai , Ross Jeremy , Choi Jun Yong ,   IeDEA Asia‐Pacific
Published: February 2019

Introduction

Multiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries.

Methods

Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in‐line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure.

Results

The incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities.

Conclusions

In our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.
Chemokine-triggered microtubule polymerization promotes neutrophil chemotaxis and invasion but not transendothelial migration
Authors: Yadav Sandeep Kumar , Stojkov Darko , Feigelson Sara W , Roncato Francesco , Simon Hans-Uwe , Yousefi Shida , Alon Ronen
Published: February 2019

Microtubules (MTs) are critically involved in the transport of material within cells, but their roles in chemotactic leukocyte motility and effector functions are still obscure. Resting neutrophils contain few MTs assembled in an MT organizing center (MTOC) behind their multilobular nuclei. Using a probe of real-time tubulin polymerization, SiR-tubulin, we found that neutrophils elongated their MTs within minutes in response to signals from the two prototypic chemotactic peptides, CXCL1 and fMLP. Taxol, a beta-tubulin binding and MT stabilizing drug, was found to abolish this CXCL1- and fMLP-stimulated MT polymerization. Nevertheless, taxol treatment as well as disruption of existing and de novo generated MTs did not impair neutrophil protrusion and squeezing through IL-1β-stimulated endothelial monolayers mediated by endothelial deposited CXCL1 and neutrophil CXCR2. Notably, CXCL1-dependent neutrophil TEM was not associated with neutrophil MT polymerization. Chemokinetic neutrophil motility on immobilized CXCL1 was also not associated with MT polymerization, and taxol treatment did not interfere with this motility. Nevertheless, and consistent with its ability to suppress MT polymerization induced by soluble CXCL1 and fMLP, taxol treatment inhibited neutrophil chemotaxis toward both chemotactic peptides. Taxol treatment also suppressed CXCL1- and fMLP-triggered elastase-dependent neutrophil invasion through collagen I barriers. Collectively, our results highlight de novo chemoattractant-triggered MT polymerization as key for neutrophil chemotaxis and elastase-dependent invasion but not for chemotactic neutrophil crossing of inflamed endothelial barriers.
Evolutionary implications of fetal and maternal microvillous surfaces in epitheliochorial placentae
Authors: Kazemian Ali , Hooshmandabbasi Reyhaneh , Schraner Elisabeth M. , Boos Alois , Klisch Karl
Published: February 2019

According to the “parent‐offspring conflict hypothesis” the rapid evolution and diversification of the mammalian placenta is driven by divergent optima of resource allocation between fetus and mother. The fetus has an interest to maximize its resource intake, while the mother has an interest to restrict the transfer of resources, and thus retain resources for subsequent pregnancies. In the epitheliochorial placenta, the contacting fetal and maternal surfaces at the feto‐maternal interface are covered with microvilli, which leads to an increase of membrane surfaces available for transport processes. Because membranes are the site of active transport, the conflict hypothesis predicts that the fetal surfaces at the feto‐maternal interfaces are larger than the maternal ones. We use transmission electron microscopy and a stereological method to estimate the factors by which the apical fetal and maternal membranes are enlarged by the microvilli. Ten species with an epitheliochorial placenta were studied. Focused ion beam—scanning electron microscopy (FIB‐SEM) was used to create three‐dimensional models of the interdigitating microvilli of the bovine and porcine placenta. In all species, the fetal surface was larger than the maternal. This was due to a higher number of fetal microvilli and to the presence of membrane folds at the base of the fetal, but not of maternal microvilli. Our results suggest that the ultrastructural morphology of the feto‐maternal interface in the epitheliochorial placenta is shaped by conflicting interests between fetus and mother and thus represent a so far neglected arena of the parent‐offspring conflict.