bluuebunny/crossref_metadata_2025 huggingface dataset:
MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum of rats
Authors: Zhang Haishan , Zhang Shujuan , Jia Linpei , Li Hai
Published: November 2018

Introduction

Erectile dysfunction (ED) is a common sexual problem for men and the exploration of its treatment is still in mire demand. We aim to investigate the role of the Toll‐like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the pathogenesis of angiotensin II (Ang‐II) induced ED.

Methods

Male Sprague‐Dawlay rats were treated with Ang‐II and intracavernous pressure (ICP) was measured to confirm the occurrence of ED. The corpus cavernosum penises of rats were transfected with plasmids to overexpressed MyD88. Inflammatory and vascular parameters including myeloperoxidase (MPO), cyclooxygenase2 (COX2), endothelial nitric oxide synthase (eNOS), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and cytokines in treated and untreated ED rats were measured. Flow cytometry was used to determine the apoptosis of endothelial cells of corpus cavernosum penises of rats.

Results

Ang‐II‐induced ED rats were found to contain upregulated TLR4, MyD88, MPO, and COX2, and downregulated eNOS. MyD88 overexpression deteriorates cavernous structural damage, reduces ICP and ICP/MAP values and reverses the therapeutic effect of anti‐TLR4 antibodies in rats with Ang‐II‐induced ED. Moreover, overexpression of MyD88 further upregulated MPO and COX2, downregulated eNOS, promoted oxidative stress, inflammation, and cell apoptosis rate via positively regulating the TLR4/MyD88 signaling pathway, while anti‐TLR4 antibodies downregulated MPO and COX2, upregulated eNOS, suppressed oxidative stress, inflammation, and cell apoptosis rate via inactivating the TLR4/MyD88 signaling pathway in the rat corpus cavernosum penises. Furthermore, MyD88 overexpression promotes oxidative stress and inflammation and reverses the effect of anti‐TLR4 antibodies in the penis of ED rats.

Conclusion

MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum rats.
LncRNA OIP5‐AS1 predicts poor prognosis and regulates cell proliferation and apoptosis in bladder cancer
Authors: Wang Yang , Shi Fu , Xia Yong , Zhao Huacai
Published: November 2018

Opa‐interacting protein 5 antisense RNA 1 (OIP5‐AS1) is a long intergenic noncoding RNA, which has been suggested to be dysregulated in human cancers and served as tumor suppressor or promoter depending on tumor types. However, the role of OIP5‐AS1 in bladder cancer was still unknown. In our study, OIP5‐AS1 was overexpressed in bladder cancer, and associated with clinical progression and short overall survival. The loss‐of‐function studies suggested downregulation of OIP5‐AS1 expression decreased cell viability, induced cell‐cycle arrest and promoted cell apoptosis in bladder cancer. There was a positive association between OIP5‐AS1 expression and OIP5 expression in bladder cancer tissues. Moreover, downregulation of OIP5‐AS1 expression reduced messenger RNA and protein levels of OIP5 in bladder cancer cell lines. In conclusion, OIP5‐AS1 is a useful biomarker for predicting clinical progression and poor prognosis and promotes cell proliferation through modulating OIP5 expression.
A C‐type CpG ODN accelerates wound healing via regulating fibroblasts and immune response
Authors: Li Lina , Xu Zhenyu , Zuo Jian , Ding Jin
Published: November 2018

Abolished or delayed wound healing is a serious problem in clinical surgery, therefore, the new therapy for wound healing is needed. Synthetic oligodeoxynucleotides containing one or more CpG motifs (CpG ODN) has been reported to activate the immune system and improves skin wound healing. The aim of the present study was to evaluate the role of a new C‐type CpG ODN in wound healing. We found that the CpG ODN promoted cell proliferation and collagen I production in human skin fibroblasts cells. Besides, we also investigated the effect of CpG ODN on the activation of immune cells. The macrophages and plasmacytoid dendritic cells (pDCs) were incubated with CpG ODN. CpG ODN activated macrophage and pDCs via regulating TLR9/MyD88/NF‐κB pathway and TLR9/MyD88/IRF7 pathway, respectively. To further evaluate the effect of CpG ODN on wound healing in vivo a wound healing model was established in mice. The results showed that CpG ODN treatment accelerated wound healing in mice. CpG ODN increased cytokines secretion in wound skin and elevated the ratio of CD4
+ and CD8
+ T cells in the spleen. Our results showed that CpG ODN accelerated wound healing, which was partly due to the regulation of fibroblasts and immune response. The findings suggested that the CpG ODN might be a proper medicament for the treatment of wound healing.
miR‐377‐5p inhibits lung cancer cell proliferation, invasion, and cell cycle progression by targeting AKT1 signaling
Authors: Wu Han , Liu Hai Yan , Liu Wen Jie , Shi Yong Li , Bao Dawei
Published: November 2018

Lung carcinoma is the most common type of malignant tumors globally, and its molecular mechanisms remained unclear. With the aim to investigate the effects of microRNA (miR)‐377‐5p on the cell development, invasion, metastasis, and cycle of lung carcinoma, this study was performed. We evaluated miR‐377‐5p expression levels in lung cancer tissues and cell models. Cell viability, proliferation, migration, invasion abilities, and cell cycle distribution were measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, crystal violet, transwell, and flow cytometry assay. Furthermore, expression levels of protein kinase B α subunit (AKT1) and proteins related to cell cycle and epithelial‐mesenchymal transition (EMT) were assessed using Western blot analysis and quantitative real‐time polymerase chain reaction. These results suggested that miR‐377‐5p was downregulated in vivo and in cell models, and miR‐377‐5p overexpression inhibited cell viability, proliferation, migration, invasion, and induced cell‐cycle arrest. In addition, as a target of miR‐377‐5p, AKT1 alleviated the decreases of cell viability, proliferation, migration, invasion, the S‐phase cells, the expression of cyclin D1, fibronectin, and vimentin, as well as the increases of the G0/G1‐phase cells, the expression of Foxo1, p27
kip1, p21
Cip1 and E‐cadherin when miR‐377‐5p overexpressed. In conclusion, miR‐377‐5p inhibited cell development and regulated cell cycle distribution and EMT by targeting AKT1, which provided a theoretical basis for further study of lung carcinoma therapeutics.
Epigenetic and metabolic alterations in human amniotic fluid stem cells induced to cardiomyogenic differentiation by DNA methyltransferases and p53 inhibitors
Authors: Gasiūnienė Monika , Zubova Anastasija , Utkus Algirdas , Navakauskienė Rūta
Published: November 2018

Human amniotic fluid‐derived mesenchymal stem cells (AF‐MSCs) may be a valuable source for cell therapy and regenerative medicine. In this study, the potential of DNA methyltransferases (DNMT) inhibitors Decitabine, Zebularine, RG108 alone or combined with Zebularine and p53 inhibitor Pifithrin‐α to induce cardiomyogenic differentiation of AF‐MSCs was investigated. Differentiation into cardiomyocyte‐like cells initiation was indicated with all agents by changes in the cell phenotype, upregulation of the relative expression of the main cardiac genes (NKX2‐5,
TNNT2,
MYH6, and
DES) as well as of cardiac ion channels genes (sodium, calcium, and potassium) as determined by reverse‐transcription quantitative polymerase chain reaction and the increase in Connexin43 levels as detected from Western blot and immunofluorescence data. Cellular energetics and mitochondrial function in induced cells were assessed using Seahorse analyzer and revealed the initiation of AF‐MSCs metabolic transformation into cardiomyocyte‐like cells. All used inducers were nontoxic to AF‐MSCs, arrested cell cycle at the G0/G1 phase, and upregulated p53 and p21 expression. The relative expression of miR‐34a and miR‐145 that are related to cell cycle regulation was also observed. Furthermore, the evaluated levels of chromatin remodeling proteins enhancer of zeste homolog 2, suppressor of zeste 12 protein homolog, DNMT1, histone deacetylase 1 (HDAC1), HDAC2, and heterochromatin protein 1α, as well as the rate of activating histone modifications, exhibited rearrangements of chromatin after the induction of cardiomyogenic differentiation. In conclusion, we demonstrated that all explored DNMT and p53 inhibitors initiated cardiomyogenesis‐related alterations in AF‐MSCs through rather similar mechanisms but to a different extent providing useful insights for the future research and potential applications of AF‐MSCs.
Carvacrol suppresses inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes
Authors: Li Yu , Xu Jian‐zhong , Gu Chen‐xi , Liu Guan‐lei , Tian Ke
Published: November 2018

Background

Fibroblast‐like synoviocytes (FLSs) play an essential role in the chronic inflammatory process of rheumatoid arthritis (RA). Carvacrol is a natural monoterpenic phenol that retains significant anti‐inflammatory activity. However, the effect of carvacrol on inflammatory response in RA‐FLSs has not yet been reported. The present study aimed to investigate the role of carvacrol in lipopolysaccharides (LPS)‐induced inflammatory response in human RA‐FLSs.

Methods

Cell viability and proliferation were measured by MTT and Cell Counting Kit‐8 assays, respectively. The migration was detected by transwell assay. The production of inflammatory cytokines and matrix metalloproteinases (MMPs) were analyzed by enzyme‐linked immunosorbent assay. The expressions of toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), NF‐κB, p38, p‐p38, ERK1/2, p‐ERK1/2, c‐Jun N‐terminal kinase (JNK), and p‐JNK were detected by Western blot analysis.

Results

Carvacrol‐inhibited LPS‐induced cell proliferation and migration of RA‐FLSs. The production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)− 6, and IL‐8, was reduced by carvacrol in LPS‐induced RA‐FLSs. Meanwhile, the induction of MMPs, including MMP‐1, MMP‐3, and MMP‐13, caused by LPS stimulation was inhibited by carvacrol in RA‐FLSs. Furthermore, carvacrol prevented LPS‐induced activation of the TLR4/MyD88/NF‐κB, p38, and ERK1/2 pathways in RA‐FLSs.

Conclusions

Carvacrol‐mitigated LPS‐induced cell proliferation, migration, and inflammation in RA‐FLSs. The TLR4/MyD88/NF‐κB, p38 and ERK1/2 pathways might be involved in the protective effect of carvacrol.
Transient receptor potential melastatin 2–antisense RNA is overexpresed in osteosarcoma and regulates cell proliferation and apoptosis
Authors: Geng Jie , Lu Ming , Li Wuyin
Published: November 2018

Accumulating evidence suggested that transient receptor potential melastatin 2–antisense RNA (TRPM2‐AS) played crucial roles in the progression of human cancers. However, the role of TRPM2‐AS was still unknown in osteosarcoma. The aim of this study was to explore the clinical significance of TRPM2‐AS in osteosarcoma patients, and determine the role of TRPM2‐AS on osteosarcoma cell proliferation and apoptosis. In our results, we identified a novel oncogenic long noncoding RNA TRPM2‐AS, which was overexpressed in osteosarcoma tissues and cells, and correlated with advanced Enneking stage, large tumor size and high histological grade in osteosarcoma cases. Survival analysis indicated that osteosarcoma patients with high TRPM2‐AS expression had an obviously shorter overall survival time than those with low TRPM2‐AS expression. Loss‐of‐function studies suggested that suppression of TRPM2‐AS expression inhibited osteosarcoma cell proliferation and induced cell apoptosis through upregulating cleaved caspase‐3 and cleaved caspase‐9 expression. In conclusion, TRPM2‐AS acts as an oncogenic long noncoding RNA and predicts poor prognosis in osteosarcoma.
A panel of noncoding RNAs in non–small‐cell lung cancer
Authors: Bagheri Abouzar , Khorshid Hamid Reza Khorram , Tavallaie Mahmood , Mowla Seyed Javad , Sherafatian Masih , Rashidi Mohsen , Zargari Mehryar , Boroujeni Mahdi Eskandarian , Hosseini Sayed Mostafa
Published: November 2018

Non–small‐lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC could pave the way for effective therapies. Analysis of molecular genetic biomarkers in biological fluids has been proposed as a useful tool for cancer diagnosis. Here, we aimed to develop a panel of noncoding RNAs (ncRNAs) in sputum for NSCLC early detection. Expression of 11 ncRNAs were analyzed by real–time polymerase chain reaction in sputum samples of 30 NSCLC patients and 30 sex‐ and age‐matched cancer‐free controls. Stability of endogenous microRNAs (miRNAs) in sputum was evaluated after 3 and 6 days at 4°C, 6 months, and 1 year at −80°C. Nine ncRNAs showed significant differences of their expression in sputum between NSCLC patients and controls. A logistic regression model with the best prediction was built based on miR‐145, miR‐126, and miR‐7. The composite of the three miRNAs produced 90% sensitivity and specificity in distinguishing NSCLC patients from the controls. Results indicate that miRNAs could be useful biomarkers based on their stability under various storage conditions and maintain differential changes between cancer and control groups. Moreover, measurement of miRNAs in sputum could be a noninvasive approach for detection of lung cancer.
MicroRNA‐194 overexpression protects against hypoxia/reperfusion‐induced HK‐2 cell injury through direct targeting Rheb
Authors: Shen Yan , Zhao Yan , Wang Lijun , Zhang Wenjing , Liu Chao , Yin Aiping
Published: November 2018

Renal ischemia‐reperfusion injury, a major cause of renal failure, always leads to acute kidney injury and kidney fibrosis. MicroRNAs (miRs) have been reported to be associated with renal ischemia‐reperfusion injury. miR‐194 was downregulated following renal ischemia‐reperfusion injury; however, the function and mechanism of miR‐194 in renal ischemia‐reperfusion injury have not yet been fully understood. In the present study, we constructed renal ischemia‐reperfusion injury model in vitro through treatment of human kidney proximal tubular epithelial cells HK‐2 by hypoxia/reperfusion (H/R). We observed that miR‐194 was decreased in H/R‐induced HK‐2 cells. miR‐194 mimic increased H/R‐induced HK‐2 cell survival, whereas miR‐194 inhibitor further strengthened H/R‐ inhibited HK‐2 cell survival. Also, we observed that miR‐194 overexpression suppressed oxidative stress markers, including malondialdehyde, glutathione, and secretion of pro‐inflammatory cytokines, including IL‐6, IL‐1β, and TNF‐α; however, miR‐194 inhibitor showed the reverse effects. Results from dual‐luciferase analysis confirmed that Ras homology enriched in brain (Rheb) was a direct target of miR‐194. Finally, we corroborated that miR‐194 affected cell growth, oxidative stress, and inflammation through targeting Rheb in H/R‐induced HK‐2 cells. In conclusion, our results suggested that miR‐194 protect against H/R‐induced injury in HK‐2 cells through direct targeting Rheb.
Retracted: MicroRNA‐373 promotes the development of endometrial cancer by targeting LATS2 and activating the Wnt/β‐Catenin pathway
Authors: Li Yan , Sun Dongxia , Gao Jie , Shi Zhimin , Chi Pengyu , Meng Yuanyuan , Zou Changjun , Wang Yanhua
Published: November 2018

In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA‐373 (miR‐373) in different human cancers draw our attention. In the present research, upregulation of miR‐373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR‐373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/β‐Catenin pathways were also investigated, which were promoted by overexpression of miR‐373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR‐373. LATS2 was verified as a direct target gene of miR‐373 through luciferase reporter assay. Especially, the facilitation of miR‐373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR‐373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/β‐Catenin pathway.
Selenoprotein S protects against high glucose‐induced vascular endothelial apoptosis through the PKCβII/JNK/Bcl‐2 pathway
Authors: Yu Shanshan , Liu Xiaoying , Men Lili , Yao Junjie , Xing Qian , Du Jianling
Published: November 2018

Vascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress‐induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)‐induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up‐ or downregulated in HUVECs using the pcDNA3.1‐SelS recombinant plasmid and SelS‐specific small interfering RNAs, and the effects of high/low SelS expression on HG‐induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG‐induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CβII (PKCβII), c‐JUN N‐terminal kinase (JNK), and B‐cell lymphoma/leukemia‐2 (Bcl‐2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG‐induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCβII, JNK, and Bcl‐2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG‐induced apoptosis, and this was achieved through the inhibition of PKCβII/JNK/Bcl‐2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.
Identification of key biomarkers in diabetic nephropathy via bioinformatic analysis
Authors: Zeng Mengru , Liu Jialu , Yang Wenxia , Zhang Shumin , Liu Fuyou , Dong Zheng , Peng Youming , Sun Lin , Xiao Li
Published: November 2018

Diabetic nephropathy (DN) is a major cause of end‐stage renal disease. Although intense efforts have been made to elucidate the pathogenesis, the molecular mechanisms of DN remain to be clarified. To identify the candidate genes in the progression of DN, microarray datasets GSE30122, GSE30528, and GSE47183 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein‐protein interaction network was constructed and the module analysis was performed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. A total of 61 DEGs were identified. The enriched functions and pathways of the DEGs included glomerulus development, extracellular exosome, collagen binding, and the PI3K‐Akt signaling pathway. Fifteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in acute inflammatory response, inflammatory response, and blood vessel development. Correlation analysis between unexplored hub genes and clinical features of DN suggested that COL6A3, MS4A6A,PLCE1, TNNC1, TNNI1, TNN2, and VSIG4 may involve in the progression of DN. In conclusion, DEGs and hub genes identified in this study may deepen our understanding of molecular mechanisms underlying the progression of DN, and provide candidate targets for diagnosis and treatment of DN.
Serum markers in the differential diagnosis of Waldenstrom macroglobulinemia and other IgM monoclonal gammopathies
Authors: Zou Hong , Yang Rong , Liao Zhong‐xian , Qin Tian‐di , Chen Ping , Zhang Bei‐ying , Cao Ying‐ping , Huang Hui‐fang
Published: November 2018

Background

IgM monoclonal gammopathy can be present in a broad spectrum of diseases. We evaluated the value of serum markers in the differential diagnosis of Waldenstrom macroglobulinemia (WM) and other types of IgM monoclonal gammopathies.

Methods

We included patients who were first admitted to hospital and identified as having IgM monoclonal gammopathy by serum immunofixation electrophoresis (sIFE). We evaluated basic clinical features, sIFE, diagnosis, and serum markers. Furthermore, we applied the receiver operating characteristic (ROC) curve to analyze the differential diagnosis value of serum markers for WM. Finally, we used logistic regression and ROC curve to analyze the differential diagnosis value of multimarker combinations to identify WM.

Results

IgM monoclonal gammopathy was most frequently found in patients with Waldenstrom macroglobulinemia, followed by monoclonal gammopathy of undetermined significance (MGUS), B‐cell non‐Hodgkin Lymphoma (B‐NHL), and multiple myeloma (MM). Serum markers showed significant differences among the four diseases. The diagnostic markers LDH, IgM, IgG, IgA, and serum light chain К had higher diagnostic efficiency. Among these markers, serum IgM provided the highest diagnostic efficiency. Additionally, the combined use of all five serum markers provided the most effective diagnosis.

Conclusions

The five serum markers, LDH, IgM, IgG, IgA, and К, each yielded a specific efficacy in differential diagnosis of WM. The single marker with the highest diagnostic efficiency was the serum IgM level. However, a combination of multiple serum markers was better than the use of a single marker in diagnosing WM. The combined use of all five serum markers provided the most effective diagnosis, with an AUC of .952 and sensitivity and specificity of 87.8% and 86.9%, respectively.
Reasons for nonadherence and response to treatment in an adherence intervention trial for relapsing–remitting multiple sclerosis patients
Authors: Schoor Rachel , Bruce Amanda , Bruce Jared , Goggin Kathy , Schanfarber Bethany , Bradley‐Ewing Andrea , Thelen Joanie , Glusman Morgan , Lynch Sharon G. , Strober Lauren , Catley Delwyn
Published: November 2018

Objectives

To explore whether patients in an adherence trial who appeared not to take disease modifying therapy (DMT) for avoidance reasons could be reliably identified, by observational coding, for their main reason of not taking DMT. To determine whether reason groups could be distinguished by clinical and self‐report psychological characteristics and intervention outcomes.

Method

Participants were multiple sclerosis patients (N = 78, 88.5% female, mean age 45.64) demotivated to take DMT. Audio recordings of the sessions were coded for the main reason of not taking DMT. Reason groups were compared based on patient characteristics and intervention outcomes.

Results

Avoidance and three other reasons for not taking DMT (side effects, cost, and mild course) were reliably identified (κ = 0.88). Patient characteristics failed to distinguish participants in the Avoidance group, which also had poorer outcomes (X2 [2, n = 73] = 6.35, p = 0.036).

Conclusions

Patients not taking DMT for avoidance reasons may need novel methods to identify them and encourage (re‐)initiation.
Downregulation of microRNA‐592 protects mice from hypoplastic heart and congenital heart disease by inhibition of the Notch signaling pathway through upregulating KCTD10
Authors: Pang Xue‐Feng , Lin Xue , Du Jian‐Jun , Zeng Ding‐Yin
Published: November 2018

Evidence has demonstrated that the microRNA (miR) may play a significant role in the development of congenital heart disease (CHD). Here, we explore the mechanism of microRNA‐592 (miR‐592) in heart development and CHD with the involvement of KCTD10 and Notch signaling pathway in a CHD mouse model. Cardiac tissues were extracted from CHD and normal mice. Immunohistochemistry staining was performed to detect positive expression rate of KCTD10. A series of inhibitor, activators, and siRNAs was introduced to verified regulatory functions for miR‐592 governing KCTD10 in CHD. Furthermore, the effect of miR‐592 on cell proliferation and apoptosis was also investigated. Downregulated positive rate of KCTD10 was observed in CHD mice. Downregulation of miR‐592 would upregulate expression of KCTD10 and inhibit the activation of Notch signaling pathway, thus promote cell proliferation. This study demonstrates that downregulation of miR‐592 prevents CHD and hypoplastic heart by inhibition of the Notch signaling pathway via negatively binding to KCTD10.
Retracted: MicroRNA‐99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Li Yong‐Jie , Wang Yue , Wang Yi‐Ying
Published: November 2018

Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR‐99b‐5p (miR‐99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray‐based analysis was used to screen out differentially expressed miRNAs. Expression of miR‐99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR‐99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR‐99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR‐99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR‐99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR‐99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.
Identification of hsa‐mir‐34a, hsa‐mir‐124, and hsa‐mir‐204 as signatures for cataract
Authors: Wei Ying‐Li , Sun Hao
Published: November 2018

Cataract, one of the common age‐related diseases that remains the leading cause of blindness worldwide. There have been studies pertaining to microRNA (miRNA) effects on cataract pathogenesis. However, the results were different from each other due to the influence of sequencing platform, sample selection, filter conditions, and so on. This study aims to explore the key miRNAs underlying the pathogenesis of cataract and find prevention and treatment methods. First, six representative cataract miRNA datasets are selected and the key miRNAs are determined. The target genes of these key miRNAs are predicted using the TargetScan software, and then, the functional enrichment and transcription factor binding analysis of these target genes are completed, respectively. Three signature miRNAs associated with cataract are finally identified. Among them, hsa‐mir‐34a seems to be significantly upregulated, while hsa‐mir‐124 and hsa‐mir‐204 are significantly downregulated. The target genes of the signature miRNAs are mainly enriched in hsa04015:Rap1 signaling pathway, hsa04142:lysosome, and hsa04360:axon guidance, indicating that these pathways may be the crucial metabolic pathways. To summarize, three key miRNAs related to cataract pathogenesis are identified, and the corresponding target genes and transcription factors are also analyzed. Moreover, the potential functions of the target genes are revealed. The results of this study may contribute to the targeted therapy of cataract through miRNAs.
CircRNA ZNF609 functions as a competitive endogenous RNA to regulate FOXP4 expression by sponging miR‐138‐5p in renal carcinoma
Authors: Xiong Yunhe , Zhang Jiabin , Song Chao
Published: November 2018

Circular RNA (circRNA) play important roles in the pathological processes of many diseases. By analyzing the results of the GSE100186 chip, we found that the expression of circRNA ZNF609 (circ‐ZNF609) was significantly increased in renal cell carcinoma. Recently, there are studies showing that circ‐ZNF609 can regulate cell proliferation and invasion ability of various cells. In this study, we investigated whether circ‐ZNF609 may affect cell invasion and proliferation in renal carcinoma. Quantitative reverse transcription polymerase chain reaction was performed to detect the expression of circ‐ZNF609 in renal carcinoma cell lines and renal epithelial cells. The direct interaction between microRNA‐138‐5p (miR‐138‐5p) and forkhead box P4 (FOXP4) or circ‐ZNF609 was confirmed by luciferase reporter assay and RNA immunoprecipitation assay. We use Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and Matrigel assays to assess the effect of miR‐138‐5p or circ‐ZNF609 on cell proliferation or invasion ability. And we found that circ‐ZNF609 is significantly increased in renal carcinoma cell lines. In addition, the high expression of circ‐ZNF609 promotes cell proliferation and invasion ability. In short, our current study reveals the role of the circ‐ZNF609/miR‐138‐5p/FOXP4 regulatory network in renal carcinoma and provides a new perspective for the pathogenesis of renal carcinoma.
A novel infram deletion in MSH6 gene in glioma: Conversation on MSH6 mutations in brain tumors
Authors: Deris Zayeri Zeinab , Tahmasebi Birgani Maryam , Mohammadi Asl Javad , Kashipazha Davood , Hajjari Mohammadreza
Published: November 2018

Objective and background

Histological and molecular information and biopsy help in the diagnosis of the type and grade of tumors and increase the value of estimation of the biological behavior of tumors. In this study, we focused on a consanguineous Iranian Family with high prevalence of brain tumors in their pedigree and reviewed the literature on MSH6 mutations in brain tumors and the treatment responses focused on Gliomas.

Method

We chose a family with a high prevalence of brain tumor in their pedigree. We studied the proband's neuroimaging and brain proton magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), biopsy result, and whole‐genome sequencing.

Result

The neuroimaging and brain proton MRS reported a lesion in the right frontoparietal. The MRI revealed a large enhancible heterogenous mass in the right temporo‐fronto‐parieto‐occipital lobes with involvement of corpus callosum which was suggestive of glioma. The patient revealed a homozygous pattern for a novel 9 base‐pare deletion at the 912–914 codon on exon 4 of the MSH6 gene.

Discussion

We discuss several studies on MSH6 mutations in brain tumors and we discuss treatment responses in MSH6 mutations and the studies conducted to sensitize chemotherapy and radiotherapy resistance brain tumors to face this subject efficiently.

Conclusion

Patients should be evaluated for MMR mutation before chemo and radiotherapy, and it is valuable to follow‐up these mutations during the treatment too. In temozolomide (TMZ)‐resitance cases, it is suggested to use complementary strategies such as using HDACis and a combination of a STAT3 Inhibitor and an mTOR inhibitor, BER inhibition mechanism, and PARP‐1 inhibitor.
The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis
Authors: Shirazi Mohammad Khabbaz , Azarnezhad Asaad , Abazari Mohammad Foad , Poorebrahim Mansour , Ghoraeian Pegah , Sanadgol Nima , Bokharaie Hanieh , Heydari Sahar , Abbasi Amin , Kabiri Sahra , Aleagha Maryam Nouri , Enderami Seyed Ehsan , Dashtaki Amir Savar , Askari Hassan
Published: November 2018

The interplay between H2S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide‐a donor of H
2S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+
L‐NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N‐acetyl‐b‐glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω‐nitro‐l‐arginine methyl ester (
L‐NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H
2S in the kidney. Moreover, the study suggests that NO, in an isoform‐dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.
PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells
Authors: Lu Yu Cheng , Wang Pu , Wang Jie , Ma Ronald , Lee Shao Chin
Published: November 2018

We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and centrosome translocation of rho‐associated coiled‐coil containing protein kinase 1 (ROCK1)/14‐3‐3σ complex in HCT116 cells. In the functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using HCT116 cells. We found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered the centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14‐3‐3σ. Individual knockdown of PCNA, NPM, or 14‐3‐3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment‐increased expression of ROCK1, whereas knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin, and palmitic acid also increased the expressions of c‐Jun N‐terminal kinase‐1 (JNK1) and signal transducer and activator of transcription 3 (Stat3), individual knockdown of which upregulated the treatment‐increased expression of 14‐3‐3σ and promoted the centrosome amplification. In contrast, overexpression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14‐3‐3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment‐increased expression of Stat3. Knockdown of PCNA, JNK1, or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1‐Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex, and NPM serves as an independent signal for the centrosome amplification.
Toward a Dignity Architecture: The Critical Challenges of Stigmatized‐Identity Cues for Consumer Psychology
Authors: Lamberton Cait
Published: November 2018

As Chaney, Sanchez, and Maimon (2019—this issue) detail, the prevalence of anti‐stigmatization cues may encourage us to believe that a more inclusive marketplace is on the horizon. This commentary argues that, unfortunately, three barriers have limited the effectiveness of these cues, and that each constitutes a call to serious inquiry for a wide range of consumer researchers. First, marketers have done little to reach out to the most severely stigmatized groups, limiting the degree to which inclusive marketing can effect real societal change. Second, researchers have not systematically articulated reasons that anti‐stigmatization cues may fall flat or even backfire, leaving practitioners little guidance in designing effective cues. Finally, studying stigmatization presents methodological challenges, and may feel like a minefield to researchers not well‐versed in complex issues of sexuality, race and ethnicity. If we are willing to address such barriers, however, I argue that we can build a framework for a “dignity architecture.” Like choice architecture, this framework highlights the nonneutrality of marketing actions in experience design, ultimately offering guidance for affirming consumer worth.
A note on a Brooks' type theorem for DP‐coloring
Authors: Kim Seog‐Jin , Ozeki Kenta
Published: November 2018

Dvořák and Postle introduced DP‐coloring of simple graphs as a generalization of list‐coloring. They proved a Brooks' type theorem for DP‐coloring; and Bernshteyn, Kostochka, and Pron extended it to DP‐coloring of multigraphs. However, detailed structure, when a multigraph does not admit DP‐coloring, was not specified. In this note, we make this point clear and give the complete structure. This is also motivated by the relation to signed coloring of signed graphs.
On dihedral flows in embedded graphs
Authors: Litjens Bart
Published: November 2018

Let be a multigraph with for each vertex a cyclic order of the edges incident with it. For , let be the dihedral group of order . Define . Goodall et al in 2016 asked whether admits a nowhere‐identity ‐flow if and only if it admits a nowhere‐identity ‐flow with (a “nowhere‐identity dihedral ‐flow”). We give counterexamples to this statement and provide general obstructions. Furthermore, the complexity of deciding the existence of nowhere‐identity ‐flows is discussed. Lastly, graphs in which the equivalence of the existence of flows as above is true are described. We focus particularly on cubic graphs.
Eco‐friendly Polyethylene Glycol‐400 as a Rapid and Efficient Recyclable Reaction Medium for the Synthesis of Anticancer Isatin‐linked Chalcones and Their 3‐Hydroxy Precursor
Authors: Gupta Alpana K. , Bharadwaj Mausumi , Mehrotra Ravi
Published: November 2018

Isatin chalcones and their 3‐hydroxy precursors are shown to possess potential anticancer activity and are also versatile substrates and key intermediates for the synthesis of a large variety of bioactive spiro‐oxindoles. An environmental friendly tandem synthesis, using PEG 400 as green solvent cum phase transfer catalyst, for a series of 3‐hydroxy‐2‐oxindoles and 3‐methylene‐2‐oxindoles has been developed. Reported one‐pot sustainable synthetic strategy was compared with the conventional method and was found to be superior to existing two‐step syntheses in terms of simplicity, product yield, and reaction time and have a large substrate scope.
Kinetics of antigen‐specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients
Authors: Zhao Ling‐Zhai , Hong Wen‐Xin , Wang Jian , Yu Lei , Hu Feng‐Yu , Qiu Shuang , Yin Chi‐Biao , Tang Xiao‐Ping , Zhang Lin‐Qi , Jin Xia , Zhang Fu‐Chun
Published: November 2018

Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection.
Hydrologic responses to projected climate change in ecologically diverse watersheds of the Gulf Coast, United States
Authors: Neupane Ram P. , Ficklin Darren L. , Knouft Jason H. , Ehsani Nima , Cibin Raj
Published: November 2018

The Gulf Coast watersheds in the United States contain some of the highest levels of biodiversity of all freshwater systems in North America. Developing environmental management policies to protect and preserve these ecosystems makes the study of the impacts of projected climate change on the future hydrologic cycle crucial. We used the Soil and Water Assessment Tool (SWAT) to estimate the potential hydrologic changes for the mid‐21st century (2050s) and the late 21st century (2080s) in the Mobile River, Apalachicola River, and Suwannee River watersheds in the Gulf Coast region of the United States. These estimates are based on downscaled future climate projections from 20 global circulation models (GCMs) under two representative concentration pathways (RCPs 4.5 and 8.5). SWAT models were calibrated and validated using the multi‐algorithm, genetically adaptive multi‐objective (AMALGAM) technique in a high‐performance computing (HPC) cluster. For the Gulf Coast watersheds, the climate is projected to be warmer and wetter. Projected changes in climatic variables are likely to bring large changes in both annual and seasonal hydrologic processes within these watersheds. We found substantial decreases in mean annual streamflow under RCP8.5 during the 2080s, with up to a 13.0% decrease projected for the Suwannee River watershed compared to the present day. Summer streamflow is projected to be substantially lower during the 2080s, with up to a 25.1% decrease projected for the Suwannee River watershed, during a time of high demand of water resources for agricultural, industrial, and ecosystem services. These hydrologic projections are expected to help in making better‐informed decisions for future water resources and ecosystem management in the Gulf Coast region.
Comparative Study of Pattern‐Based Versus Size Ratio Ultrasound Strain Elastographic Techniques on Breast Masses
Authors: Leong Lester Chee Hao , Moey Tammy Hui Lin , Tan Puay Hoon , Fook‐Chong Stephanie , Sim Llewellyn Shao‐jen
Published: November 2018

Objectives

The aim of this study was to compare the diagnostic performance of strain elastographic techniques involving pattern‐based elastography versus size ratio elastography on breast masses.

Methods

Female patients presenting to the radiology department for ultrasound (US)‐guided biopsies, fine‐needle aspirations, or localizations of breast masses were invited to undergo US elastographic assessments of the lesions before the breast procedures. The masses were evaluated for color score and color map size ratio elastographic assessments with one US machine and size ratio and grayscale strain pattern elastographic assessments with another machine. With the histopathologic diagnosis as the reference standard, the sensitivity, specificity, and area under the receiver operating characteristic curve were compared among the 4 groups.

Results

A total of 154 breast masses from 139 women were assessed. The sensitivity and specificity were 0.615 (95% confidence interval, 0.470–0.747) and 0.824 (0.736–0.892), respectively for the color score, 0.962 (0.868–0.995) and 0.765 (0.670–0.843) for the size ratio, 0.904 (0.790–0.968) and 0.745 (0.649–0.826) for the color map size ratio, and 0.635 (0.490–0.764) and 0.422 (0.324–0.523) for the grayscale strain pattern. The areas under the receiver operating characteristic curve were 0.729 for the color score, 0.874 for the size ratio (P = .001 with the color score as a reference), 0.836 for the color map size ratio (P = .002), and 0.556 for the grayscale strain pattern (P < .001).

Conclusions

Size ratio elastography had higher sensitivity and better diagnostic accuracy compared to color score elastography. This superiority was demonstrated on two different US systems, and size ratio elastography should thus be considered over color score elastography in the adjunctive US assessment of breast lesions.
Vocal motor control and central auditory impairments in unilateral vocal fold paralysis
Authors: Naunheim Molly L. , Yung Katherine C. , Schneider Sarah L. , Henderson‐Sabes Jennifer , Kothare Hardik , Mizuiri Danielle , Klein David J. , Houde John F. , Nagarajan Srikantan S. , Cheung Steven W.
Published: November 2018

Objectives

To evaluate differences in vocal motor control and central auditory processing between treated unilateral vocal fold paralysis (UVFP) and healthy control cohorts.

Study Design

Cross‐sectional.

Methods

Ten UVFP study patients treated by type I thyroplasty with stable voices were compared to 12 control subjects for vocal motor control using a pitch perturbation response task and central auditory processing performance using a battery of complex sound intelligibility assays that included adverse temporal and noise conditions. Standard clinical evaluations of voice production and peripheral audiometric sensitivity were performed.

Results

Vocal motor control was impaired in treated UVFP. The UVFP cohort exhibited a 32.5% reduction in the instantaneous, subconscious compensatory response to pitch feedback perturbation in the interval between 150 ms and 550 ms following onset (P < 0.0001, linear mixed effects model). This impairment cannot simply be ascribed to vocal motor capacity insufficiency in the UVFP cohort because both cohorts demonstrated comparable functional capacity to perform the vocal motor task. The UVFP cohort also showed greater propensity for central auditory processing impairment (P < 0.05), notably for temporal compression and added noise challenges.

Conclusion

Combined central vocal motor control and auditory processing impairments in treated UVFP highlight reciprocal interdependency of sensory and motor systems. This pilot study suggests that peripheral motor impairment of the larynx can degrade central auditory processing, which in turn may contribute to vocal motor control impairment. A more complete restoration communicative function in UVFP will require deeper understanding of sensory, motor, and sensorimotor aspects of the human communication loop.

Level of Evidence

3b

Laryngoscope, 129:2112–2117, 2019