bluuebunny/crossref_metadata_2025 huggingface dataset:
Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor
Authors: Samadi Pouria , Afshar Saeid , Amini Razieh , Najafi Rezvan , Mahdavinezhad Ali , Sedighi Pashaki Abdolazim , Gholami Mohammad Hadi , Saidijam Massoud
Published: December 2018

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.
MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential
Authors: Mardani Rajab , Jafari Najaf Abadi Mohammad Hassan , Motieian Mahsa , Taghizadeh‐Boroujeni Sima , Bayat Amir , Farsinezhad Alireza , Gheibi Hayat Seyed Mohammad , Motieian Mahtab , Pourghadamyari Hossein
Published: December 2018

Leukemia is known as a progressive malignant disease, which destroys the blood‐forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR‐15, miR‐16, let‐7, and miR‐127) or oncogene (i.e., miR‐155, miR‐17‐92, miR‐21, miR‐125b, miR‐93, miR‐143‐p3, miR‐196b, and miR‐223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.
Protective effects of either C‐peptide or l‐arginine on pancreatic β‐cell function, proliferation, and oxidative stress in streptozotocin‐induced diabetic rats
Authors: Ragy Merhan Mamdouh , Ahmed Sabreen Mahmoud
Published: December 2018

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C‐peptide or l‐arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1—control nondiabetic, 2—diabetic (no treatment), 3—diabetic + C‐peptide, and 4—diabetic + 
l‐arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B‐cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C‐peptide or
l‐arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C‐peptide treatment of the diabetic rats completely corrected these errors, while
l‐arginine partially antagonized the above diabetic complications. So the administration of C‐peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.
Intracellular delivery of nucleic acid by cell‐permeable hPP10 peptide
Authors: Ding Yi , Zhao Xueli , Geng Jingping , Guo Xiangli , Ma Jielan , Wang Hu , Liu Changbai
Published: December 2018

Although gene therapy offers hope against incurable diseases, nonreplicating transduction vectors remain lacking. We have previously characterized a cell‐penetrating peptide hPP10 for the delivery of various cargoes; however, whether hPP10 can mediate nucleic acid delivery is still unknown. Here, examining via different ways, we demonstrate that hPP10 stably complexes with plasmid DNA (pDNA) and safely mediates nucleic acid transfection. hPP10 can mediate GFP‐, dsRed‐, and luciferase‐expressing plasmids into cells with nearly the same efficiency as commercial transfection reagents Turbofectin or Lipofect. Furthermore, hPP10 can mediate Cre fusion protein delivery and pDNA transfection simultaneously in the Cre/loxp system in vitro. In addition, hPP10 fused with an RNA‐binding domain can mediate delivery of small interfering RNA into cells to silence the reporter gene expression. Collectively, our results suggest that hPP10 is an option for nucleic acid delivery with efficiencies similar to that of commercial reagents.
Inhibition of microRNA‐129‐5p expression ameliorates ultraviolet ray‐induced corneal epithelial cell injury via upregulation of EGFR
Authors: Yang Ying , Gong Bo , Wu Zheng‐Zheng , Shuai Ping , Li Dong‐Feng , Liu Ling‐Lin , Yu Man
Published: December 2018

Existing evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA‐129‐5p (miR‐129‐5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray‐induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR‐129‐5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR‐positive expression rate. The dual‐luciferase reporter gene assay was used to test whether EGFR could directly target miR‐129‐5p. To further investigate the specific mechanism of miR‐129‐5p and EGFR in CEC injury, CECs were cultured and transfected with miR‐129‐5p mimic, miR‐129‐5p inhibitor, siRNA‐EGFR, and miR‐129‐5p inhibitor + siRNA‐EGFR. miR‐129‐5p has been proven to directly target EGFR. Inhibition of miR‐129‐5p is able to increase the antioxidant capacity, EGFR‐positive rate and the expressions of EGFR, B‐cell lymphoma‐2, zonula occluden‐1, occludin, and keratinocyte growth factor‐2, but decrease the expression of vascular endothelial growth factor, BCL2‐associated X protein, interleukin (IL)‐1β, and IL‐4. Inhibition of miR‐129‐5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR‐129‐5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR‐129‐5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.
RUNX1‐dependent mechanisms in biological control and dysregulation in cancer
Authors: Hong Deli , Fritz Andrew J. , Gordon Jonathan A. , Tye Coralee E. , Boyd Joseph R. , Tracy Kirsten M. , Frietze Seth E. , Carr Frances E. , Nickerson Jeffrey A. , Van Wijnen Andre J. , Imbalzano Anthony N. , Zaidi Sayyed K. , Lian Jane B. , Stein Janet L. , Stein Gary S.
Published: December 2018

The RUNX1 transcription factor has recently been shown to be obligatory for normal development. RUNX1 controls the expression of genes essential for proper development in many cell lineages and tissues including blood, bone, cartilage, hair follicles, and mammary glands. Compromised RUNX1 regulation is associated with many cancers. In this review, we highlight evidence for RUNX1 control in both invertebrate and mammalian development and recent novel findings of perturbed RUNX1 control in breast cancer that has implications for other solid tumors. As RUNX1 is essential for definitive hematopoiesis, RUNX1 mutations in hematopoietic lineage cells have been implicated in the etiology of several leukemias. Studies of solid tumors have revealed a context‐dependent function for RUNX1 either as an oncogene or a tumor suppressor. These RUNX1 functions have been reported for breast, prostate, lung, and skin cancers that are related to cancer subtypes and different stages of tumor development. Growing evidence suggests that RUNX1 suppresses aggressiveness in most breast cancer subtypes particularly in the early stage of tumorigenesis. Several studies have identified RUNX1 suppression of the breast cancer epithelial‐to‐mesenchymal transition. Most recently, RUNX1 repression of cancer stem cells and tumorsphere formation was reported for breast cancer. It is anticipated that these new discoveries of the context‐dependent diversity of RUNX1 functions will lead to innovative therapeutic strategies for the intervention of cancer and other abnormalities of normal tissues.
Effect of Gpx3 gene silencing by siRNA on apoptosis and autophagy in chicken cardiomyocytes
Authors: Gong Yafan , Yang Jie , Cai Jingzeng , Liu Qi , Zhang Jun min , Zhang Ziwei
Published: December 2018

Glutathione peroxidase 3 (Gpx3), as an important selenoprotein, is the most crucial antioxidant defense in cardiomyocytes. However, the role of Gpx3 in Se‐deficient cardiomyocyte damage still less reported. Here, we developed Gpx3 silence cardiomyocytes culture model (small interfering RNA; siRNA) for research the crosstalk between autophagy and apoptosis. Quantitative real‐time PCR and western blot analysis are performed to detect the expression of apoptosis and autophagy‐related genes. MDC stain, flow cytometry, AO/EB stain, and electron microscope were performed to observe the changes of cell morphology. Our results reveal that Gpx3 suppression can significant increases in ROS (p < 0.05) levels, which further induced apoptosis through upregulated the expression of Caspase‐3 in cardiomyocytes. Meanwhile, we also found that the whole process is accompanied by the occurrence of autophagy, which are promoted by inhibiting the mTOR, and increasing the expression of ATG‐7, ATG‐10, and ATG‐12. Altogether, we conclude that the apoptotic and autophagic response machineries share antagonistic function in Gpx3 knockdown cardiomyocytes.
Antidiabetic potential of saffron and its active constituents
Authors: Yaribeygi Habib , Zare Vahid , Butler Alexandra E. , Barreto George E. , Sahebkar Amirhossein
Published: December 2018

The prevalence of diabetes mellitus is growing rapidly worldwide. This metabolic disorder affects many physiological pathways and is a key underlying cause of a multitude of debilitating complications. There is, therefore, a critical need for effective diabetes management. Although many synthetic therapeutic glucose‐lowering agents have been developed to control glucose homeostasis, they may have unfavorable side effects or limited efficacy. Herbal‐based hypoglycemic agents present an adjunct treatment option to mitigate insulin resistance, improve glycemic control and reduce the required dose of standard antidiabetic medications. Saffron (Crocus sativus L.), whilst widely used as a food additive, is a natural product with insulin‐sensitizing and hypoglycemic effects. Saffron contains several bioactive β carotenes, which exert their pharmacological effects in various tissues without any obvious side effects. In this study, we discuss how saffron and its major components exert their hypoglycemic effects by induction of insulin sensitivity, improving insulin signaling and preventing β‐cell failure, all mechanisms combining to achieve better glycemic control.
Oncolytic adenovirus: A tool for cancer therapy in combination with other therapeutic approaches
Authors: Goradel Nasser Hashemi , Mohajel Nasir , Malekshahi Ziba Veisi , Jahangiri Samira , Najafi Masoud , Farhood Bagher , Mortezaee Keywan , Negahdari Babak , Arashkia Arash
Published: December 2018

Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue‐ or tumor‐specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach.
Upregulated microRNAs in membranous glomerulonephropathy are associated with significant downregulation of IL6 and MYC mRNAs
Authors: Barbagallo Cristina , Passanisi Roberta , Mirabella Federica , Cirnigliaro Matilde , Costanzo Arianna , Lauretta Giovanni , Barbagallo Davide , Bianchi Cristina , Pagni Fabio , Castorina Sergio , Granata Antonio , Di Pietro Cinzia , Ragusa Marco , Malatino Lorenzo S. , Purrello Michele
Published: December 2018

Membranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b‐9 (complement membrane‐attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low‐Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real‐Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let‐7a‐5p, let‐7b‐5p, let‐7c‐5p, let‐7d‐5p, miR‐107, miR‐129‐3p, miR‐423‐5p, miR‐516‐3p, miR‐532‐3p, and miR‐1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let‐7a‐5p or let‐7c‐5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.
Evaluation of efficacy on RANKL induced osteoclast from RAW264.7 cells
Authors: Song Chengchao , Yang Xiaobin , Lei Yongsheng , Zhang Zhen , Smith Wanli , Yan Jinglong , Kong Lingbo
Published: December 2018

Established RAW264.7 cell lines for osteoclastic differentiation has been widely engaged in bone homeostasis research, however, the efficacy of RANKL independently stimulating has rarely been defined, because protocols were usually developed and modified by various laboratories. Otherwise, problematic issues are also lie in the cell's seeding density, RANKL stimulating time point, and distinguishing osteoclastogenesis ability of RANKL‐treated RAW264.7 cells. Therefore, in the current study, we examined the efficacy of various concentrations of RANKL‐treated RAW264.7 for its osteoclastic differentiation with or without pretreated other costimulators such as: LPS and/or M‐CSF. The oteoclastogenesis ability of RANKL‐treated RAW264.7 cells was demonstrated by bone resorption pit, F‐actin, and osteoclastogenesis specific marker studies. Besides that, through tartrate‐resistant acid phosphatase (TRAP) staining, we clarified to start the treatment with 30 ng/ml RANKL at 12 hr after seeded RAW264.7 with the density of 6.25 × 10
3 cells/cm
2 manifested an significantly increased number of multinucleated osteoclastic cells. Overall, our results establishing an optimal method for RANKL independently inducing RAW 264.7 cell osteoclastic differentiation, which could efficiently generate osteoclasts in vitro for significant advances in our understanding of bone biology.
Evaluation of ovarian cancer risk in granulosa cells treated with steroid‐depleted endometriosis serum: Role of NF‐κB/RelA and AKT
Authors: Asghari Samira , Valizadeh Dizajeykan Amir , Ahmadi Majid , Barzegari Abolfazl , Rikhtegar Reza , Dolati Sanam , Danaii Shahla , Abdollahi‐Fard Sedigheh , Nouri Mohammad , Mahdipour Mahdi , Yousefi Mehdi
Published: December 2018

Background

Despite at the beginning known as a benign disease, endometriosis is defined as a risk factor for developing ovarian carcinoma. The effect of endometriosis on ovarian malignancy is known but its role in granulosa cell tumor is still unclear.

Methods and Materials

In this study, serum samples were collected from patients with endometriosis and divided into whole and steroid‐depleted groups. Desertification was performed according to the charcoal–dextran protocol and sera were added to the culture media of granulosa cells retrieved from tubal or male factor infertile women. Quantitative real‐time polymerase chain reaction and flow cytometry were performed to determine the expression level of inflammatory and apoptotic genes and apoptosis level of granulosa cells. The total concentration of lipid was measured using gas chromatography method in the granulosa cells.

Results

Results revealed that the expression of AKT and NF‐κB/RelA gene was significantly higher in the granulosa cells treated with steroid‐depleted serum obtained from patients with distrificated endometriosis (DE) compared with the control group (9.39‐ and 7.9‐folds, respectively; p < 0.0001). In the DE group, the declined pattern of expression was observed for the genes related to apoptosis. The synthesis of saturated fatty acids was significantly decreased; however, unsaturated fatty acids showed increased levels in the DE group.

Conclusion

The effect of steroids on endometriosis is contradictory. The level of cortisol and sex hormones could be affected by endometriosis, causing alterations of the disease progression. Reduced level of steroid hormones in patients with endometriosis may be considered as a critical risk factor for granulosa cell tumor.
Recent advances in TMEM16A: Structure, function, and disease
Authors: Ji Qiushuang , Guo Shuai , Wang Xuzhao , Pang Chunli , Zhan Yong , Chen Yafei , An Hailong
Published: December 2018

TMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium‐activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single‐particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca2+ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A.
Alpinate Oxyphyllae extracts enhance the longevity and homing of mesenchymal stem cells and augment their protection against senescence in H9c2 cells
Authors: Chang Yung‐Ming , Asokan Shibu Marthandam , Tsai Chuan‐Te , Tsai Chin‐Chuan , Lin Shu‐Luan , Chang Chia‐Cheng , Viswanadha Vijaya Padma , Chen Ray‐Jade , Chang Julia Huei‐Mei , Huang Chih‐Yang
Published: December 2018

Adipose‐derived mesenchymal stem cells (ADMSCs) are easily accessible and are attractive mesenchymal stem cells for use in regenerative medicine; however their application is frequently restricted due to various challenges present in the environment they are administered. Therefore ADMSCs are preferably preconditioned with various stimulating factors to overcome the barriers developed in any pathological conditions. Here we used ADMSCs from rat adipose based on the abundance of positive markers and preconditioned the cells with extracts from Alpinate Oxyphyllae Fructus (AOF), a traditional Chinese herb used for antiaging, associated various health benefits. The preconditioned stem cells were tested for their potential to drive H9c2 from doxorubicin (Dox)‐induced aging. The AOF‐treated stem cells enriched stemness in ADMSCs with respect to their stem cells' positive marker, and enhanced their longevity mechanism and elevated the stem cell homing‐associated C‐X‐C chemokine receptor type 7 (CXCR7). The AOF preconditioned stem cells, when cocultured with H9c2 cells, showed effective protection to Dox‐induced senescence and stem cell homing to damaged H9c2 cells. The presence of AOF provided greater protective effects in the Dox environment. In addition, AOF‐pretreated ADMSCs showed enhanced migration than those treated with AOF in Dox environment. Therefore, our results show that administration of AOF preconditioned stem cells is potentially an effective strategy in the management of aging‐associated cardiac disorders.
Cajaninstilbene acid inhibits osteoporosis through suppressing osteoclast formation and RANKL‐induced signaling pathways
Authors: Sun Youqiang , Liu Yuhao , He Wei , Wang Chao , Tickner Jennifer , Kuek Vincent , Zhou Chi , Wang Haibin , Zou Xuting , Hong Zhinan , Yang Fan , Shao Min , Chen Leilei , Xu Jiake
Published: December 2018

Osteoporosis is a form of osteolytic disease caused by an imbalance in bone homeostasis, with reductions in osteoblast bone formation, and augmented osteoclast formation and resorption resulting in reduced bone mass. Cajaninstilbene acid (CSA) is a natural compound derived from pigeon pea leaves. CSA possesses beneficial properties as an anti‐inflammatory, antibacterial, antihepatitis, and anticancer agent; however, its potential to modulate bone homeostasis and osteoporosis has not been studied. We observed that CSA has the ability to suppress RANKL‐mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose‐dependent manner. Mechanistically, it was revealed that CSA attenuates RANKL‐activated NF‐κB and nuclear factor of activated T‐cell pathways and inhibited phosphorylation of key signaling mediators c‐Fos, V‐ATPase‐d2, and ERK. Moreover, in osteoclasts, CSA blocked RANKL‐induced ROS activity as well as calcium oscillations. We further evaluated the therapeutic effect of CSA in a preclinical mouse model and showed that in vivo treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA.
Characterization of an in vitro model to study the possible role of polyomavirus BK in prostate cancer
Authors: Villani Sonia , Gagliano Nicoletta , Procacci Patrizia , Sartori Patrizia , Comar Manola , Provenzano Maurizio , Favi Evaldo , Ferraresso Mariano , Ferrante Pasquale , Delbue Serena
Published: December 2018

Prostate cancer (PCa) is the most common male neoplasms in the Western world. Various risk factors may lead to carcinogenesis, including infectious agents such as polyomavirus BK (BKPyV), which infects the human renourinary tract, establishes latency, and encodes oncoproteins. Previous studies suggested that BKPyV plays a role in PCa pathogenesis. However, the unspecific tropism of BKPyV and the lack of in vitro models of BKPyV‐infected prostate cells cast doubt on this hypothesis. The aim of the present study was to determine whether BKPyV could (a) infect normal and/or tumoral epithelial prostate cells and (b) affect their phenotype. Normal epithelial prostate RWPE‐1 cells and PCa PC‐3 cells were infected with BKPyV for 21 days. Cell proliferation, cytokine production, adhesion, invasion ability, and epithelial‐to‐mesenchymal transition (EMT) markers were analyzed. Our results show that (a) RWPE‐1 and PC‐3 cells are both infectable with BKPyV, but the outcome of the infection varies, (b) cell proliferation and TNF‐α production were increased in BKPyV‐infected RWPE‐1, but not in PC‐3 cells, (c) adhesion to matrigel and invasion abilities were elevated in BKPyV‐infected RWPE‐1 cells, and (d) loss of E‐cadherin and expression of vimentin occurred in both uninfected and infected RWPE‐1 cells. In conclusion, BKPyV may change some features of the normal prostate cells but is not needed for maintaining the transformed phenotype in the PCa cells The fact that RWPE‐1 cells exhibit some phenotype modifications related to EMT represents a limit of this in vitro model.
HDAC10 upregulation contributes to interleukin 1β‐mediated inflammatory activation of synovium‐derived mesenchymal stem cells in temporomandibular joint
Authors: Liao Wenting , Sun Jiadong , Liu Wenjing , Li Wenyu , Jia Jiaxin , Ou Farong , Su Kai , Zheng Youhua , Zhang Zhiguang , Sun Yangpeng
Published: December 2018

Histone deacetylases (HDACs) are important in chronic inflammation, and inflammatory responses affect synovium‐derived mesenchymal stem cell (SMSC) function in temporomandibular joint repair. However, the effect of HDACs on SMSC inflammatory activation remains unclear. In this study, temporomandibular joint fibroblast‐like synoviocytes obtained from osteoarthritis patients met the minimal mesenchymal stem cell criteria. Interleukin 1β (IL‐1β) upregulated IL‐6 and IL‐8 expression in SMSCs through nuclear factor‐κB (NF‐κB) pathway activation. IL‐6 and IL‐8 upregulation were blocked by broad‐acting HDAC inhibitors SAHA and LBH589. MC1568 alleviated IL‐1β activation of SMSCs, whereas CI994 and FK228 produced a minimal or opposite effect in vitro. We also found HDAC10 was highly associated with localized IL‐1β expression in vivo and in vitro. HDAC10 knockdown alleviated IL‐1β‐mediated SMSC activation and blocked NF‐κB pathway activation. Conversely, HDAC10 overexpression promoted IL‐6 and IL‐8 expression and IL‐1β‐mediated NF‐κB pathway activation. In conclusion, HDAC10 upregulation contributed to IL‐1β‐mediated inflammatory activation of SMSCs, indicating that HDAC10 may be a novel therapeutic target.
Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis
Authors: Madhi Raed , Rahman Milladur , Taha Dler , Mörgelin* Matthias , Thorlacius Henrik
Published: December 2018

Recent evidence suggests that neutrophil extracellular traps (NETs) play an important role in the development of acute pancreatitis (AP). Herein, we examined the role of peptidylarginine deiminase (PAD), which has been shown to regulate NET formation, in severe AP. AP was induced by retrograde of taurocholate infusion into pancreatic duct in C57BL/6 mice. PAD was pharmacologically inhibited using Cl‐amidine, a pan‐PAD inhibitor. Pancreata were collected, and histones, citrullinated histone 3, chemokines, myeloperoxidase, and NETs were quantified. Chemokines, matrix metalloproteinase‐9 (MMP‐9), interleukin‐6 (IL‐6), and DNA‐histone complexes were determined in plasma samples. Infusion of taurocholate induced formation of NETs in pancreatic tissues of mice. Pretreatment with Cl‐amidine markedly reduced the NET formation in the inflamed pancreas. Moreover, inhibition of PAD decreased the levels of blood amylase as well as edema, acinar cell necrosis, hemorrhage, and neutrophil infiltration in the pancreas of animals with AP. Administration of Cl‐amidine attenuated the myeloperoxidase levels in the pancreas and lung of mice exposed to taurocholate. In addition, Cl‐amidine decreased pancreatic levels of CXC chemokines, plasma levels of IL‐6, and MMP‐9 in mice with severe AP. This study shows that Cl‐amidine is a potent inhibitor of NET formation in severe AP. Also, our results suggest that PAD regulates pathological inflammation and tissue damage in the inflamed pancreas. Thus, targeting PAD might be a useful strategy to treat patients with severe AP.
Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways
Authors: Moradi‐Marjaneh Reyhaneh , Hassanian Seyed Mahdi , Mehramiz Mehraneh , Rezayi Majid , Ferns Gordon A. , Khazaei Majid , Avan Amir
Published: December 2018

Reactive oxygen species (ROS) are produced by mitochondria during metabolism. In physiological states, the production of ROS and their elimination by antioxidants are kept in balance. However, in pathological states, elevated levels of ROS interact with susceptible cellular target compounds including lipids, proteins, and DNA and deregulate oncogenic signaling pathways that are involved in colorectal cancer (CRC) carcinogenesis. Although antioxidant compounds have been successfully used in the treatment of CRC as prevention approaches, they have also been shown in some cases to promote disease progression. In this review, we focus on the role of ROS in gastrointestinal homeostasis, CRC progression, diagnosis, and therapy with particular emphasis on ROS‐stimulated pathways.
Serum‐reduced media impacts on cell viability and protein expression in human lung epithelial cells
Authors: Rashid Mahamud‐ur , Coombs Kevin M.
Published: December 2018

Serum starvation is a widely used condition in molecular biology experiments. Opti‐MEM is a serum‐reduced media used during transfection of genetic molecules into mammalian cells. However, the impact of such media on cell viability and protein synthesis is unknown. A549 human lung epithelial cell viability and morphology were adversely affected by growing in Opti‐MEM. The cellular protein levels of chloride intracellular channel protein 1, proteasome subunit alpha Type 2, and heat shock 70 kDa protein 5 were dysregulated in A549 cells after growing in serum‐reduced media. Small interfering RNA transfection was done in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum, and knockdown efficacy was determined compared with Opti‐MEM. Similar amounts of knockdown of the target proteins were achieved in DMEM, and cell viability was higher compared with Opti‐MEM after transfection. Careful consideration of the impact of Opti‐MEM media during the culture or transfection is important for experimental design and results interpretation.
Tears and ocular surface disorders: Usefulness of biomarkers
Authors: Di Zazzo Antonio , Micera Alessandra , De Piano Maria , Cortes Magdalena , Bonini Stefano
Published: December 2018

Introduction

Corroborating data suggest that the analysis of tear fluid might represent an additional tool in the ophthalmological practice.

Areas Covered

The purpose of this review was to sum up the tear protein profiles in healthy and diseased ocular surface and to highlight biomarker usefulness in the early diagnosis as well as at follow‐up. This analysis encompasses a deep examination of the protein profile expression under physiological and pathological conditions. Tear protein profile analysis will allow in the near future discriminating between different grades of inflammation, from acute trauma toward immune‐, endocrine‐, and nervous‐related disorders of the ocular surface.

Concluding Remarks

The review provides an overview of old and recent findings about inflammatory mediators identified at the ocular surface, under physiological and pathological conditions. To date, the analysis of tear fluid represents a new additional approach for diagnosis and management of ocular surface diseases. Understanding the pathophysiological mechanism could also offer significant advantages to develop strategies addressed to better clarify some complex ocular surface disorders. To sum up, the possibility to provide selective biomarkers as a future target of specific diseases should be considered for supporting diagnosis and management of ocular surface diseases.
A novel antifouling ultrafiltration membranes prepared from percarboxylic acid functionalized SiO2 bound Fe3O4 nanoparticle (SCMNP‐COOOH)/polyethersulfone nanocomposite for BSA separation and dye removal
Authors: Vatanpour Vahid , Shahsavarifar Samaneh , Khorshidi Sohrab , Masteri‐Farahani Majid
Published: December 2018

BACKGROUND

Silica coated magnetite nanoparticles (SCMNPs) were synthesized via a co‐precipitating method and functionalized with carboxylic acid and percarboxylic acid groups for the preparation of microporous polyethersulfone (PES) nanocomposite membranes and used in bovine serum albumin (BSA) and dye separation. There is no published report about the use of this nanoparticle in the preparation of mixed matrix membranes.

RESULTS

Different concentrations of these nanoparticles were used. The 0.5 wt% SCMNPs‐COOOH NPs–PES membrane had the lowest irreversible fouling resistance (Rir) value (8.33%) and the highest FRR value (91.7%), suggesting that the prepared mixed matrix membrane is easily recovered by water washing. The introduction of percarboxylic acid groups has a positive impact on rejection of the three dyes (Rhodamine B, Direct Black 38, Reactive Green 19), and all membranes presented rejections of more than 90% due to improved electrostatic repulsion between the dye and the membrane surface by incorporation of the nanoparticles.

CONCLUSION

The membranes modified by SCMNPs‐COOOH had significantly higher permeability and BSA solution flux compared with the bare PES membrane. The nanocomposite membranes had enhanced hydrophilicity because of water affinity enhancement of the membrane surface due to the presence of hydrophilic nanoparticles. It is concluded that SCMNPs‐COOOH nanoparticles could be an ideal additive to modify PES membrane for water filtration applications. © 2018 Society of Chemical Industry
Design and Synthesis of Some New Benzimidazole Containing Pyrazoles and Pyrazolyl Thiazoles as Potential Antimicrobial Agents
Authors: Bakthavatchala Reddy Nemallapudi , Zyryanov Grigory V. , Mallikarjuna Reddy Guda , Balakrishna Avula , Padmaja Adivireddy , Padmavathi Venkatapuram , Suresh Reddy Cirandur , Garcia Jarem Raul , Sravya Gundala
Published: December 2018

A new class of bis heterocycles‐benzimidazolyl pyrazoles were prepared from the Michael acceptor (E)‐3‐(1H‐benzimidazol‐2‐yl)‐1‐aryl‐prop‐2‐en‐1‐one. The thiamide group was exploited to develop thiazole ring on treatment with p‐fluorophenacyl bromide to get tris heterocycles. All the lead compounds were tested for antimicrobial activity. The compound 7d having nitro substituent on the aromatic ring showed greater antimicrobial activity particularly against Pseudomonas aeruginosa and Penicillium chrysogenum.
Impact of a borderless sample transport network for scaling up viral load monitoring: results of a geospatial optimization model for Zambia
Authors: Nichols Brooke E , Girdwood Sarah J , Crompton Thomas , Stewart‐Isherwood Lynsey , Berrie Leigh , Chimhamhiwa Dorman , Moyo Crispin , Kuehnle John , Stevens Wendy , Rosen Sydney ,   EQUIP Health
Published: December 2018

Introduction

The World Health Organization recommends viral load (VL) monitoring at six and twelve months and then annually after initiating antiretroviral treatment for HIV. In many African countries, expansion of VL testing has been slow due to a lack of efficient blood sample transportation networks (STN). To assist Zambia in scaling up testing capacity, we modelled an optimal STN to minimize the cost of a national VL STN.

Methods

The model optimizes a STN in Zambia for the anticipated 1.5 million VL tests that will be needed in 2020, taking into account geography, district political boundaries, and road, laboratory and facility infrastructure. We evaluated all‐inclusive STN costs of two alternative scenarios: (1) optimized status quo: each district provides its own weekly or daily sample transport; and (2) optimized borderless STN: ignores district boundaries, provides weekly or daily sample transport, and reaches all Scenario 1 facilities.

Results

Under both scenarios, VL testing coverage would increase to from 10% in 2016 to 91% in 2020. The mean transport cost per VL in Scenario 2 was $2.11 per test (SD $0.28), 52% less than the mean cost/test in Scenario 1, $4.37 (SD $0.69), comprising 10% and 19% of the cost of a VL respectively.

Conclusions

An efficient STN that optimizes sample transport on the basis of geography and test volume, rather than political boundaries, can cut the cost of sample transport by more than half, providing a cost savings opportunity for countries that face significant resource constraints.
The chemokine receptor CXCR2 contributes to murine adipocyte development
Authors: Dyer Douglas P , Nebot Joan Boix , Kelly Christopher J , Medina-Ruiz Laura , Schuette Fabian , Graham Gerard J
Published: December 2018

Chemokines are members of a large family of chemotactic cytokines that signal through their receptors to mediate leukocyte recruitment during inflammation and homeostasis. The chemokine receptor CXCR2 has largely been associated with neutrophil recruitment. However, there is emerging evidence of roles for chemokines and their receptors in processes other than leukocyte migration. We have previously demonstrated that CXCR2 knockout (KO) mice have thinner skin compared to wild-type mice. Herein we demonstrate that this is due to a thinner subcutaneous adipose layer, as a result of fewer and smaller individual adipocytes. We observe a similar phenotype in other fat depots and present data that suggests this may be due to reduced expression of adipogenesis related genes associated with adipocyte specific CXCR2 signaling. Interestingly, this phenotype is evident in female, but not male, CXCR2 KO mice. These findings expand our understanding of nonleukocyte related chemokine receptor functions and help to explain some previously observed adipose-related phenotypes in CXCR2 KO mice.
Exploring aggregation‐induced emission through tuning of ligand structure for picomolar detection of pyrene
Authors: Ghosh Milan , Ta Sabyasachi , Lohar Sisir , Das Sudipta , Brandão Paula , Felix Vitor , Das Debasis
Published: December 2018

Tuning of ligand structures through controlled variation of ring number in fused‐ring aromatic moiety appended to antipyrine allows detection of 7.8 × 10−12 M pyrene via aggregation‐induced emission (AIE) associated with 101‐fold fluorescence enhancement. In one case, antipyrine unit is replaced by pyridine to derive bis‐methylanthracenyl picolyl amine. The structures of four molecules have been confirmed by single crystal X‐ray diffraction analysis. Among them, pyrene‐antipyrine conjugate (L) undergoes pyrene triggered inhibition of photo‐induced electron transfer (PET) leading to water‐assisted AIE.
VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg‐positive chronic hepatitis B patients treated with pegylated interferon
Authors: Shan Ben , Wang Jun Yan , Wang Xia , Fu Juan Juan , Li Li , Pan Xiu Cheng , Li Jian Jun , Tang Xian Tuan
Published: December 2018

Aim

To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg‐IFN) in hepatitis B early antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients.

Methods

One hundred and nineteen HBeAg‐positive CHB patients who received Peg‐IFN monotherapy for 48 weeks and then were followed‐up for another 48 weeks were prospectively enrolled; baseline 25‐hydroxy vitamin D (25‐(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped.

Results

Forty‐five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow‐up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294‐0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243‐0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215‐0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203‐0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103‐0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077‐0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634‐0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/
ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024‐3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057‐12.029; P = 0.040).

Conclusions

Genetic variation of VDR rs7975232/
ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg‐positive CHB patients with Peg‐IFN monotherapy.
Allograft reconstruction of the humerus: Complications and revision surgery
Authors: Ogink Paul T. , Teunissen Frederik R. , Massier Julie R. , Raskin Kevin A. , Schwab Joseph H. , Lozano‐Calderon Santiago A.
Published: December 2018

Background and Objectives

Allograft reconstruction of the humerus after resection is preferred by many because of bone stock restoration and biologic attachment of ligaments and muscles to the allograft, theoretically obtaining superior stability and functionality. Our aim was to assess the prevalence of complications and the incidence and etiology for revision surgery in humeral allograft reconstructions.

Methods

We included patients 18 years and older who underwent wide resection and allograft reconstruction of the humerus for primary and metastatic lesions at our institution between 1990 and 2013. Our primary outcome measures were complications and revision surgery. We used competing risk regression to assess allograft survival.

Results

Of the 84 patients we included, 47 patients (51%) underwent allograft reconstructions of the proximal humerus, 30 (36%) intercalary, and seven (8%) of the distal humerus. Fifty‐one patients (61%) had at least one complication after surgery. Eighteen patients (21%) underwent revision surgery. The 5‐year allograft survival was 71%.

Conclusion

Although allograft reconstructions of the humerus are a valuable option in the orthopedic oncologist's armamentarium, surgeons should mind the accompanying complication rates. Allograft fractures seem to be the main issue for proximal and distal allografts, often leading to revision surgery. Intercalary allografts are mostly troubled by nonunions.
Vertical head impulse and caloric are complementary but react opposite to Meniere's disease hydrops
Authors: Fukushima Munehisa , Oya Ryohei , Nozaki Kengo , Eguchi Hirotaka , Akahani Shiro , Inohara Hidenori , Takeda Noriaki
Published: December 2018

Objectives/Hypothesis

Meniere's disease (MD) patients can show normal head impulses despite poor caloric test results. This study aimed to investigate the discrepancy in the vestibulo‐ocular reflex (VOR) in MD patients and whether endolymphatic hydrops (EH) influence the VOR.

Study Design

Prospective, cross‐sectional observational study.

Methods

Ninety MD patients were enrolled. Neuro‐otological testing, including a video head impulse test (vHIT) of all semicircular canals (SCs), and gadolinium‐enhanced inner ear magnetic resonance imaging were performed. The vestibular EH volume was quantitatively evaluated by processing magnetic resonance images.

Results

Abnormal vHIT results in MD patients were found most frequently in the posterior (44.4%) SCs, followed by the horizontal (13.3%) and anterior (10%) SCs. Canal paresis (CP) was assessed using the vHIT and the caloric test, and results were not significant when vHIT responses were assessed as CP only using the horizontal SC. The difference in the vestibular EH between the presence and absence of CP was not significant if assessed using the vHIT (P = .5591), but it was statistically different if assessed using the caloric test (P = .0467).

Conclusions

The contradictory reaction of VOR in MD patients may result from the high specificity but low sensitivity of CP in the horizontal vHIT. EH volume in the vestibule affects the caloric response but does not affect the vHIT response.

Level of Evidence

2b

Laryngoscope, 129:1660–1666, 2019