bluuebunny/crossref_metadata_2025 huggingface dataset:
Disposable Microfluidic Sensor Based on Nanocellulose for Glucose Detection
Authors: Uddin Khan Mohammad Ahsan , Jokinen Ville , Jahangiri Farzin , Franssila Sami , Rojas Orlando J. , Tuukkanen Sampo
Published: November 2018

Point‐of‐care devices that are inexpensive, disposable, and environmentally friendly are becoming increasingly predominant in the field of biosensing and biodiagnostics. Here, microfluidics is a suitable option to endow portability and minimal reagent and material consumption. Nanocellulose is introduced to manufacture microfluidic channels and as a storage and immobilization compartment of glucose oxidase. Improved enzymatic activity retention is demonstrated in a simple and disposable point‐of‐care diagnostic unit that is able to detect glucose from fluid matrices at 0.1 × 10−3m concentration and in less than 10 min. It is concluded that the patterning and fluidic technologies that are possible with nanocellulose enable easily scalable multianalyte designs.
Does global drug innovation correspond to burden of disease? The neglected diseases in developed and developing countries
Authors: Barrenho Eliana , Miraldo Marisa , Smith Peter C.
Published: November 2018

Although it is commonly argued that there is a mismatch between drug innovation and disease burden, there is little evidence on the magnitude and direction of such disparities. In this paper, we measure inequality in innovation, by comparing research and development activity with population health and gross domestic product data across 493 therapeutic indications to globally measure: (a) drug innovation, (b) disease burden, and (c) market size.

We use concentration curves and indices to assess inequality at two levels: (a) broad disease groups and (b) disease subcategories for both 1990 and 2010.

For some top burden disease subcategories (i.e., cardiovascular and circulatory diseases, neoplasms, and musculoskeletal disorders), innovation is disproportionately concentrated in diseases with high disease burden and large market size, whereas for others (i.e., mental and behavioral disorders, neonatal disorders, and neglected tropical diseases) innovation is disproportionately concentrated in low burden diseases.

These inequalities persisted over time, suggesting inertia in pharmaceutical research and development in tackling the global health challenges.

Our results confirm quantitatively assertions about the mismatch between disease burden and pharmaceutical innovation in both developed and developing countries and highlight the disease areas for which morbidity and mortality remain unaddressed.
The Odor Value Concept in the Formal Analysis of Olfactory Art
Authors: Kraft Philip
Published: November 2018

In the past 15 years, there has been a tremendous increase in the emergence of olfactory artworks despite the traditional skepticism with respect to scents as subjects of art. This essay submits that this skepticism lacks aesthetic justification; art is what is accepted as such, and olfactory art is in fact already well accepted as an art form by the general public. However, there exists no methodological tool for the formal analysis of olfactory artworks. The essay suggests such a method, based on odor values; this is elaborated using the fragrance‘Dune’ (Dior, 1991), and is compared with a purely visual approach to the same subject. This new concept allows for the derivation of simple compositional sketches and is then exemplified by the formal analysis of three more recent olfactory artworks:Elodie Pong/Roman Kaiser, ‘White‘ (2016),Martynka Wawrzyniak/Yann Vasnier, ‘Tears (T6)’ (2012), andChristophe Laudamiel, ‘heat’ (2003).
Effectiveness of a dissemination strategy on the uptake of an online menu planning program: A controlled trial
Authors: Grady Alice , Wolfenden Luke , Rissel Chris , Green Sue , Reilly Kathryn , Yoong Sze Lin
Published: November 2018

Issue addressed

Online systems offer opportunities to provide effective, ongoing support to childcare services to implement dietary guidelines. The study aimed to assess the effectiveness of a dissemination strategy on childcare service: (i) adoption; and (ii) use of an online menu planning program designed to increase compliance with dietary guidelines.

Methods

A nonrandomised controlled trial was conducted with long day care services across Australia. All services received an email invitation to access an online evidence‐based menu planning program. Services in the intervention also received training, telephone contact and provision of a portable computer tablet to encourage program adoption and use. Outcomes were assessed at the 6‐month follow‐up using analytics data recorded by the online program. Outcomes included the proportion of services having accessed the program (adoption) and the proportion of services with a current menu entered in the program (use as intended).

Results

Twenty‐seven interventions and 19 control services took part. At the 6‐month follow‐up, 100% vs 58% of services had adopted the online menu planning program (OR: 14.67, 95% CI: 2.43‐infinity; P < 0.01) and 41% vs 5% of services had a current menu entered in the program (OR: 9.99, 95% CI: 1.01‐534.57; P < 0.01) in the intervention and control arms respectively.

Conclusions

This study highlights the need for strategies to support adoption and use of an online menu planning program in childcare services if the potential benefits of such a program are to be achieved. Future research should explore the effectiveness of differing strategies to increase adoption and use of online programs at scale.

So what?

Strategies to support childcare service uptake and use of online programs are required in order for the potential public health benefits of such technologies to be realised.
Remarkable response to abiraterone acetate in castration‐resistant prostate cancer patient with aggressive liver metastasis
Authors: Katsui Masahiro , Ohigashi Takashi , Kosaka Takeo , Bessho Hideharu , Arakawa Takashi
Published: November 2018

Introduction

The number of treatment options for metastatic castration‐resistant prostate cancer has increased in recent years. Abiraterone, which selectively inhibits CYP17 in the androgen synthesis pathway, is widely used. Liver metastasis is one of the worst prognostic factors in metastatic castration‐resistant prostate cancer. Only a few case reports have shown abiraterone successfully treated the liver metastasis of metastatic castration‐resistant prostate cancer.

Case presentation

A 62‐year‐old man with prostate‐specific antigen of 16.69 ng/mL was diagnosed with Gleason 8 (3 + 5) poorly differentiated prostate adenocarcinoma. Androgen deprivation therapy and sequential anti‐androgen replacement were performed; however, the disease advanced to castration‐resistant prostate cancer with liver metastasis. Prior to docetaxel, abiraterone achieved marked improvements in liver metastasis and prostate‐specific antigen.

Conclusion

Metastatic castration‐resistant prostate cancer patients with visceral metastasis were excluded from COU‐AA‐302, which is phase III trial on abiraterone prior to docetaxel. Although docetaxel is the recommended treatment for the visceral metastasis of castration‐resistant prostate cancer according to the European Association of Urology guidelines, abiraterone also has potential as a treatment option.
MicroRNA‐98 attenuates cardiac ischemia‐reperfusion injury through inhibiting DAPK1 expression
Authors: Zhai Chang‐Lin , Tang Guan‐Min , Qian Gang , Hu Hui‐Lin , Wang Shi‐Jun , Yin Dong , Zhang Song
Published: November 2018

Cardiovascular ischemic disease is a large class of diseases that are harmful to human health. The significant role of microRNAs (miRNAs) in terms of controlling cardiac injury has been reported in latest studies. MiR‐98 is very important in regulating the apoptosis, the differentiation, the growth as well as the metastasis of cells. Nevertheless, the effect of miR‐98 in the cardiac ischemia reperfusion (I/R) injury has rarely been investigated. In the current research, we found that the miR‐98 expression was down‐regulated in the cardiomyocytes subjected to hypoxia/reoxygenation (H/R) and in the myocardium of the I/R rats. In addition, over‐expression of miR‐98 could significantly reduce the myocardial oxidative stress and ischemic injury as well as cell apoptosis. In agreement, similar findings were demonstrated in H9c2 cells subjected to H/R injury. Bioinformatic analysis using MiRanda and TargetScan and luciferase activity assay confirmed death‐associated protein kinase 1 (DAPK1) as a direct target of miR‐98. These findings suggest that miR‐98 may be exploited as a novel molecular marker or therapeutic target for myocardial I/R injury. © 2018 IUBMB Life, 71(1):166–176, 2019
Whole‐mount in situ hybridization of mouse brain to precisely locate mRNAs via fluorescence tomography
Authors: Guo Wenyan , Liu Xiuli , Hu Qinglei , Huang Fei , Li Ning , Zhang Qi , Li Yuxin , Xiong Feng , Luo Qingming , Zeng Shaoqun
Published: November 2018

Nucleic acids of intact biological tissues are rich in biological information. Whole‐mount in situ hybridization is a powerful technique to mine the wealth of data contained in DNAs or RNAs, especially mRNAs. However, there are no simple, rapid approaches to precisely locate mRNAs in whole‐mount tissues such as intact brains. By combining the penetration procedures of iDISCO with the signal amplification approach termed hybridization chain reaction, we herein developed a method for whole‐brain in situ hybridization at cellular resolution. Based on fluorescence tomography instead of tissue clearing, this method provides a simple, rapid way to precisely locate mRNAs in the whole brain with cytoarchitectonic landmarks. As a proof of principle, we investigated the exact distribution of Cre mRNA in a Thy1‐Cre mouse brain. We found high levels of Cre mRNA in most regions of the subcortical nuclei and the brain stem but comparatively low levels in major areas of the cerebral cortex. This method may have broad applications in studies of RNA function and its relations with diseases.
On the analysis of microrheological responses of self‐assembling RADA16‐I peptide hydrogel
Authors: Seyedkarimi Mansooreh‐Sadat , Mirzadeh Hamid , Bagheri‐Khoulenjani Shadab
Published: November 2018

This work aims to obtain a hydrogel based on self‐assembling RADA16‐I with proper rheological properties for hemostasis application. Response surface methodology (RSM) was performed to predict the gelation and stiffness of the hydrogel in different concentrations of peptide and NaCl in water and blood serum milieus. Particle tracking microrheology technique was used to evaluate Brownian motion of polystyrene particles in the peptide solutions to obtain their trajectories and measure the viscoelastic properties (G′′, G″, and tanδ). Formation of gel was influenced by the concentrations of peptide and salt and their interactions. Optimum response for maximizing elastic modulus was obtained in the presence of blood serum in comparison with water. Negative effect of excess amount of NaCl was predicted by RSM model and confirmed by animal study. Circular dichroism (CD) analysis showed formation of β‐sheet secondary structure in water. On the other hand, in the presence of blood serum, tertiary structure was formed. Dimensional characterization of peptide fibers was performed by means of AFM. Peptide self‐assembly in blood serum (pH around 7) which contains different ions, led to enhancing bonds between fibers, caused increasing the fiber diameter and length by 20 and 10 times, respectively. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 330–338, 2019.
Surfactant‐assisted‐water‐exposed versus surfactant‐aqueous‐solution‐exposed electrospinning of novel super hydrophilic polycaprolactone based fibers: Analysis of drug release behavior
Authors: Zargarian Seyed Shahrooz , Haddadi‐Asl Vahid , Kafrashian Zahra , Azarnia Mojdeh , Mirhosseini Mohammad Masoud , Seyedjafari Ehsan
Published: November 2018

Surface hydrophilicity and scaffold integrity determine the drug release behavior of drug loaded electrospun fibrous mats. When mixture miscibility is acceptable, blend electrospinning of hydrophobic with hydrophilic polymers can improve scaffold hydrophilicity while the hydrophobic polymer maintains the mechanical strength of scaffold. Polycaprolactone (PCL) and Pluronic P123 (P123) blend electrospinning has been investigated. In routine blend electrospinning, surface enrichment of Pluronic sets a limit for P123 weight ratio in which exceeding from that limit causes the excess P123 to be accumulated within the electrospun fiber core. To overcome this setback, a method named surfactant assisted water exposed (SAWE) electrospinning was introduced which was proven to be effective for increasing the surface enrichment of Pluronic. In order to test the validity of this method, the electrospinning of solution containing PCL which is exposed to aqueous solution of P123 was investigated. This new method was named surfactant aqueous solution exposed (SASE) electrospinning. Myelin formation at the contact interface of aqueous solution and chloroform solution was studied and it was found that this layer can effectively barricade the migration of Pluronic chains between immiscible phases. For SASE, fiber surface coverage by P123 was uneven and loose. Electrospun scaffolds from SAWE and SASE were loaded with drug to investigate the effect of the exposure time during electrospinning on in vitro drug release. By increasing the exposure time, the abnormal two‐stage phased release profile of SAWE became normal with moderate initial burst. Longer exposure time increased the initial burst of the drug loaded SASE fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 597–609, 2019.
Polymeric ionically conductive composite matrices and electrical stimulation strategies for nerve regeneration: In vitro characterization
Authors: Manoukian Ohan S. , Stratton Scott , Arul Michael R. , Moskow Joshua , Sardashti Naseem , Yu Xiaojun , Rudraiah Swetha , Kumbar Sangamesh G.
Published: November 2018

Stem cell strategies and the use of electrical stimulation (ES) represent promising new frontiers for peripheral nerve regeneration. Composite matrices were fabricated by coating electrospun polycaprolactone/cellulose acetate micro–nanofibers with chitosan and ionically conductive (IC) polymers including, sulfonated polyaniline, and lignin sulfonate. These composite matrices were characterized for surface morphology, coating uniformity, ionic conductivity, and mechanical strength to explore as scaffold materials for nerve regeneration in conjunction with ES. Composite matrices measured conductivity in the range of 0.0049–0.0068 mS/m due to the uniform coating of sulfonated polymers on the micro–nanofibers. Thin films (2D) and composite fiber matrices (3D) of IC polymers seeded with human mesenchymal stem cells (hMSCs) were electrically stimulated at 0.5 V, 20 Hz for 1 h daily for 14 days to study the changes in cell viability, morphology, and expression of the neuronal‐like phenotype. In vitro ES lead to changes in hMSCs' fibroblast morphology into elongated neurite‐like structures with cell bodies for ES‐treated and positive control growth factor‐treated groups. Immunofluorescent staining revealed the presence of neuronal markers including β3‐tubulin, microtubule‐associated protein 2, and nestin in response to ES. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1792–1805, 2019.
The determination of the potential anticancer effects of Coriandrum sativum in PC‐3 and LNCaP prostate cancer cell lines
Authors: Elmas Levent , Secme Mücahit , Mammadov Ramazan , Fahrioglu Umut , Dodurga Yavuz
Published: November 2018

Coriander (Coriandrum sativum L.) is such an herb from the Apiaceae family, used both for its medicinal and nutritional properties for many centuries. In this study, the effects of C. sativum extract on gene expression, viability, colony formation, migration, and invasion of PC‐3 and LNCaP prostate cancer cell lines have been investigated. The half maximal inhibitory concentration (IC50) dose in PC‐3 and LNCaP cells was detected to be 2 and 5 mg/mL at the 24th hour, respectively. C. sativum extracts have been observed to cause a significant decrease in the expression of Akt and Bcl‐2 in the PC‐3 cells and just Akt in LNCaP cells while increasing in the expression of p53, caspase‐9, caspase‐10, PTEN, DR5, TRADD, PUMA, and NOXA. DR4 expression was increased in LNCaP cell line but not PC‐3, and APAF and BID had increased expression in PC‐3 but not the LNCaP cells. Our observations have shown that C. sativum extract decreased colony formation while inhibiting cell invasion and migration. Cell migration was hindered in PC‐3 but not the LNCaP cells. In conclusion, this data present a valuable addition to the very limited data available out there on the potential use of C. sativum in prostate cancer treatment.
The effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index
Authors: Rezavand Negin , Tabarok Saba , Rahimi Ziba , Vaisi‐Raygani Asad , Mohammadi Ehsan , Rahimi Zohreh
Published: November 2018

We investigated the influence of vitamin D receptor (VDR) polymorphisms and vitamin D level on the blood pressure and the risk of preeclampsia. In a case‐control study, 200 pregnant women, including 100 individuals with preeclampsia along with 100 healthy pregnant women, were studied for VDR FokI, TaqI, and BmsI polymorphisms and serum 25 (OH)‐D level using polymerase chain reaction‐restriction fragment length polymorphism method and commercial kit, respectively. The mean level of 25 (OH)‐D in preeclamptic patients was significantly lower (16.6 ± 4.2 ng/mL, P < 0.001) compared with controls (19.6 ± 3.8 ng/mL). Among all women, a significantly higher systolic blood pressure and before‐pregnancy body mass index and also lower gestational age were observed in the presence of 25 (OH)‐D level < 20 ng/mL compared with the 20 to 30 ng/mL. A significantly higher frequency of VDR FokI C allele in preeclamptic patients (83%) than controls (74%) was associated with a 1.72‐fold increased risk of preeclampsia. In all the studied individuals, the systolic and diastolic blood pressures were significantly higher in the presence of the FokI CC genotype compared with the TC and TT+TC genotypes. Neither VDR Taq1 nor VDR BmsI was associated with the risk of preeclampsia. The haplotype FokI C, TaqI C and BmsI A (CCA) compared with haplotype CTG increased the risk of preeclampsia by 1.4‐fold (P = 0.33). Our study suggests an association between VDR FokI polymorphism and an insufficient serum level of 25 (OH)‐D with the risk of preeclampsia and also the influence of insufficient 25 (OH)‐D level and VDR FokI polymorphism on maternal factors, including blood pressure.
Decellularized Wharton's jelly extracellular matrix as a promising scaffold for promoting hepatic differentiation of human induced pluripotent stem cells
Authors: Kehtari Mousa , Beiki Bahareh , Zeynali Bahman , Hosseini Fatemeh Sadat , Soleimanifar Fatemeh , Kaabi Mohammad , Soleimani Masoud , Enderami Seyed Ehsan , Kabiri Mahboubeh , Mahboudi Hossein
Published: November 2018

Liver tissue engineering as a therapeutic option for restoring of damaged liver function has a special focus on using native decellularized liver matrix, but there are limitations such as the shortage of liver donor. Therefore, an appropriate alternative scaffold is needed to circumvent the donor shortage. This study was designed to evaluate hepatic differentiation of human induced pluripotent stem cells (hiPSCs) in decellularized Wharton's jelly (WJ) matrix as an alternative for native liver matrix. WJ matrices were treated with a series of detergents for decellularization. Then hiPSCs were seeded into decellularized WJ scaffold (DWJS) for hepatic differentiation by a defined induction protocol. The DNA quantitative assay and histological evaluation showed that cellular and nuclear materials were efficiently removed and the composition of extracellular matrix was maintained. In DWJS, hiPSCs‐derived hepatocyte‐like cells (hiPSCs‐Heps) efficiently entered into the differentiation phase (G1) and gradually took a polygonal shape, a typical shape of hepatocytes. The expression of hepatic‐associated genes (albumin, TAT, Cytokeratin19, and Cyp7A1), albumin and urea secretion in hiPSCs‐Heps cultured into DWJS was significantly higher than those cultured in the culture plates (2D). Altogether, our results suggest that DWJS could provide a proper microenvironment that efficiently promotes hepatic differentiation of hiPSCs.
Cyadox regulates the transcription of different genes by activation of the PI3K signaling pathway in porcine primary hepatocytes
Authors: Guo Ju , Cui Luqing , Lu Qirong , Zhang Yinfeng , Liu Qianying , Wang Xu , Wang Yulian , Liu Zhenli , Yuan Zonghui , Dai Menghong
Published: November 2018

Cyadox, a new derivative of quinoxalines, has been ascertained as an antibiotic with significant growth promoting, low poison, quick absorption, swift elimination, brief residual period, and noncumulative effect. Seven differential expressed genes, including Insulin‐like Growth Factor‐1 (
IGF‐1),
Epidermal Growth Factor (
EGF),
Poly ADP‐ribose polymerase (
PARP),
the Defender Against Apoptotic Death 1 (
DAD1),
Complement Component 3 (
C3),
Transketolase (
TK) and a
New gene, were induced by cyadox in swine liver tissues by messenger RNA differential display reverse transcription polymerase chain reaction (DDRT‐PCR) in our laboratory. However, the signal mechanism that cyadox altered these genes expression is not completely elucidated. The signaling pathways involved in the expressions of seven genes induced by cyadox were determined in porcine primary hepatocytes by RT‐qPCR and the application of various signal pathway inhibitors. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay revealed that cyadox could stimulate proliferation of porcine primary hepatocytes in a time‐dependent manner. In porcine primary cultured hepatocytes, phosphoinositide 3‐kinase (PI3K) and transforming growth factor‐β (TGF‐β) signal pathways were the main signal pathways involved in the expressions of seven genes induced by cyadox. Taken together, these results demonstrate for the first time that seven cyadox‐related genes expressions in porcine primary hepatocytes treated with cyadox are mediated mainly through the PI3K signaling pathway, potentially leading to enhanced cell growth and cell immunity.
EGF might be the early response gene of cyadox, and a primary regulator of the other gene expressions such as
IGF‐1 and
DAD1, playing an important role in cell proliferation promoted by cyadox.
Ameliorative effects of autophagy inducer, simvastatin on alcohol‐induced liver disease in a rat model
Authors: Atef Marwa Mohamed , Hafez Yasser Mostafa , Alshenawy Hanan Alsaeed , Emam Marwa Nagy
Published: November 2018

Alcoholic liver disease (ALD) encompasses a variety of liver injuries with various underlying mechanisms but still no effective treatment. So we aimed to monitor the influence of simvastatin on alcohol‐induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect. Thirty male albino rats were randomly divided into five equal groups. Group 1 (control): received a standard diet; group 2: received simvastatin (10 mg kg−1 day
−1) once a day orally for 8 weeks; group 3: received 20% ethanol (7.9 g kg
−1 day
−1) daily orally for 8 weeks; group 4: received 20% ethanol along with same simvastatin dose daily for 8 weeks; group 5: received 20% ethanol orally for 8 weeks then received the same simvastatin dose for the next 8 weeks. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were measured. Liver tissue malondialdehyde, reduced glutathione levels, and superoxide dismutase activity were estimated. B‐cell lymphoma 2 and C/EBP homologous protein levels were evaluated by enzyme linked immunosorbent assay (ELISA). Light chain 3‐II and peroxisome proliferation‐activated receptor gamma messenger RNA expression was assessed by real‐time polymerase chain reaction. Immunohistochemical staining was performed using anti‐rat tumor necrosis factor‐alpha antibody. Our results revealed that simvastatin treatment was able to ameliorate alcohol‐induced liver damage; the improved biochemical data were confirmed by histopathological evaluation. Simvastatin being an autophagy inducer was able to prevent and reverse alcohol‐induced liver changes via induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress‐induced apoptosis. Therefore, our findings suggest that treatment with simvastatin may be a useful approach in the management strategy of ALD.
Adenosine protects pancreatic beta cells against apoptosis induced by endoplasmic reticulum stress
Authors: Shahrestanaki Mohammad Keyvanloo , Arasi Fatemeh Panahi , Aghaei Mahmoud
Published: November 2018

Chronic exposure to high glucose induces endoplasmic reticulum (ER) stress in pancreatic beta cells (PBCs). The previous evidence showed that adenosine modulate PBCs viability and insulin secretion. The aim of this study was to evaluate possible involvement of adenosine in protection of MIN6 β‐cells from Tunicamycin (Tu)‐induced ER stress.

MIN6 cells were cotreated with Tu and different concentrations of adenosine. Cell viability, proliferation, and apoptosis were evaluated using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT), 5‐bromo‐2′‐deoxyuridine (Brdu), and colony formation assays. Caspase‐12 activity was assayed using the fluorometric method. Thioflavin T (ThT) staining was used for the evaluation of protein aggregation. Insulin secretion was evaluated using specific an ELISA kit. Ca2+ mobilization assayed using Fura2/AM probe. BIP, CHOP, XBP‐1, and XBP‐1s expression in both messenger RNA (mRNA) and protein levels were evaluated using the reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blot analysis, respectively. Bcl‐2, p‐eIF2α/eIF2α, and GADD34 levels also determined with Western blot analysis.

Adenosine protected MIN6 cells against Tu‐induced ER stress in a dose‐dependent manner and increased their proliferation. Decreased caspase‐12 activity and upregulated Bcl‐2 protein may explain antiapoptotic effects of adenosine. ThT staining indicated an attenuated aggregation of misfolded proteins. Adenosine effectively increased insulin secretion in Tu‐treated cells. BIP, CHOP, XBP1, and sXBP1 expression were decreased significantly in cotreated cells, indicating alleviation of ER stress. However, adenosine potentiated the expression of GADD34 and decreased p‐eIF2α/eIF2α ratio. Adenosine increased cytosolic Ca
2+ levels, which may promote adenosine triphosphate (ATP) synthesis in mitochondria, helping ER to preserve protein hemostasis.

Taken together, adenosine upregulated Bcl‐2 and GADD34 to protect PBCs against Tu‐induced apoptosis and increase Insulin secretion.
Rab6A GTPase contributes to phenotypic modulation in pulmonary artery smooth muscle cells under hypoxia
Authors: Wang Fang , Xu Xingxiang , Tang Weian , Min Lingfeng , Yang Junjun
Published: November 2018

Previous studies have demonstrated that hypoxia can induce phenotypic modulation of pulmonary smooth muscle cells; however, the mechanisms remain unclear. The present study aimed to investigate the effect of the GTPase Rab6A‐mediated phenotypic modulation and other activities of rat pulmonary artery smooth muscle cells (RPASMCs). We revealed that Rab6A was induced by hypoxia (1% O2) and was involved in a hypoxia‐induced phenotypic switch and endoplasmic reticulum stress (ERS) in RPASMCs. After 48 hours of hypoxia, the expression of the phenotype marker protein smooth muscle actin was downregulated and vimentin (VIM) expression was upregulated. Rab6A was upregulated after 48 hours of hypoxia, and the level of glucose‐regulated protein, 78 kDa (GRP78) after 12 hours of hypoxic stimulation was also increased. After transfection with a Rab6A short interfering RNA under hypoxic conditions, the expression levels of GRP78 and VIM in RPASMCs were downregulated. Overall, hypoxia‐induced RPASMCs to undergo ERS followed by phenotypic transformation. Rab6A is involved in this hypoxia‐induced phenotypic modulation and ERS in RPASMCs.
Is neighborhood poverty harmful to every child? Neighborhood poverty, family poverty, and behavioral problems among young children
Authors: Kim Yeonwoo , Lee Sharon , Jung Hyejin , Jaime Jose , Cubbin Catherine
Published: November 2018

This longitudinal study investigates the association between neighborhood poverty and behavioral problems among young children. This study also examines whether social environments mediate the relationship between neighborhood poverty and behavioral problems. We used data from the third and fourth waves of the Fragile Families and Child Wellbeing study to assess behavioral problems separately for children who experienced no family poverty, moved out of family poverty, moved into family poverty, and experienced long‐term family poverty. Regression models assessed the effect of neighborhood poverty on behavioral problem outcomes among children aged 5 years, after controlling for sociodemographic characteristics and earlier behavioral problems. Results showed an association between neighborhood poverty and lower social cohesion and safety, which lead to greater externalizing problems among children with long‐term family poverty living in high‐poverty neighborhoods compared with those in low‐poverty neighborhoods. Policies and community resources need to be allocated to improve neighborhood social environments, particularly for poor children in high‐poverty neighborhoods.
Effects of microRNA‐217 on proliferation, apoptosis, and autophagy of hepatocytes in rat models of CCL4‐induced liver injury by targeting NAT2
Authors: Yang Cheng‐Liang , Zheng Xiao‐Li , Ye Ke , Sun Ya‐Nan , Lu Yu‐Fei , Ge Hong , Liu Hui
Published: November 2018

Liver injury is an important cause of serious liver disease. This study aims to explore the effects of miR‐217 targeting NAT2 on hepatocyte proliferation, apoptosis, and autophagy following carbon tetrachloride (CCL4)‐induced liver injury. Rat models of CCL4‐induced liver injury were established. Healthy Wistar rats were randomized into the normal, blank, negative control (NC), microRNA‐217 (miR‐217) mimic, miR‐217 inhibitor, small interfering RNA (siRNA)‐N‐acetyltransferase 2 (NAT2), and miR‐217 inhibitor + siRNA‐NAT2 groups. NAT2 activity was evaluated with reversed‐phase high‐performance liquid chromatographic method. Immunohistochemistry was used to detect NAT2 protein positive rate. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine expressions of miR‐217, NAT2, Bcl‐2, Bax, p35, LC3‐II, Becline‐1, and the ratio of caspase‐3/cleaved caspase‐3. Autophagy, proliferation, and cell cycle distribution were determined by electron microscope, CCK‐8, and flow cytometry. NAT2 protein positive rate and miR‐217, NAT2, Bcl‐2, and p35 expressions were higher and Bax, LC3‐II, and Becline‐1 expressions and the ratio of caspase‐3/cleaved caspase‐3 lower in the normal group than the other six groups. Compared with the blank and NC groups, in the miR‐217 mimic and siRNA‐NAT2 groups, Bax, LC3‐II, and Becline‐1 expressions and the ratio of caspase‐3/cleaved caspase‐3, and hepatocyte apoptosis and autophagy increased, while NAT2, Bcl‐2, and p35 expressions and hepatocyte proliferation decreased; opposite results were observed in the miR‐217 inhibitor group. Collectively, miR‐217 targeting NAT2 inhibits proliferation and promotes apoptosis and autophagy of hepatocytes in CCL4‐induced liver injury.
Integrative proteomics and immunochemistry analysis of the factors in the necrosis and repair in acetaminophen‐induced acute liver injury in mice
Authors: Feng Qin , Zhao Ningwei , Xia Wenkai , Liang ChengJie , Dai Guoxin , Yang Jian , Sun Jingxia , Liu Lanying , Luo Lan , Yang Jie
Published: November 2018

Acetaminophen (APAP) overdose‐induced acute liver injury (AILI) is a significant clinical problem worldwide, the hepatotoxicity mechanisms are well elucidated, but the factors involved in the necrosis and repair still remain to be investigated. APAP was injected intraperitoneally in male Institute of Cancer Research (ICR) mice. Quantitative proteome analysis of liver tissues was performed by 2‐nitrobenzenesulfenyl tagging, two‐dimensional‐nano high‐performance liquid chromatography separation, and matrix‐assisted laser desorption/ionization–time of flight mass spectrometry analysis. Diffrenetial proteins were verified by the immunochemistry method. 36 and 44 differentially expressed proteins were identified, respectively, at 24 hr after APAP (200 or 300 mg·kg
−1) administration. The decrease in the mitochondrial protective proteins Prdx6, Prdx3, and Aldh2 accounted for the accumulation of excessive reactive oxygen species (ROS) and aldehydes, impairing mitochondria structure and function. The Gzmf combined with Bax and Apaf‐1 jointly contributed to the necrosis. The blockage of Stat3 activation led to the overexpression of unphosphorylated Stat3 and the overproduction of Bax. The overexpression of unphosphorylated Stat3 represented necrosis; the alternation from Stat3 to p‐Stat3 in necrotic regions represented hepatocytes from death to renewal. The high expressions of P4hα1, Ncam, α‐SMA, and Cygb were involved in the liver repair, they were not only the markers of activated HSC but also represented an intermediate stage of hepatocytes from damage or necrosis to renewal. Our data provided a comprehensive report on the profile and dynamic changes of the liver proteins in AILI; the involvement of Gzmf and the role of Stat3 in necrosis were revealed; and the role of hepatocyte in liver self‐repair was well clarified.
Ectopic nerve growth factor prevents proliferation in glioma cells by senescence induction
Authors: Meco Daniela , Di Francesco Angela Maria , Melotti Linda , Ruggiero Antonio , Riccardi Riccardo
Published: November 2018

Objective

The neurotrophin nerve growth factor (NGF) affects survival, regulation and differentiation of both central and peripheral nervous system neurons. NGF exerts its effects primarily through tropomyosin receptor kinase A (TrkA), inducing a cascade of tyrosine kinase‐initiated responses. In spite of its importance, the general behavior of NGF looks contradictory: its effects can be both stimulatory and inhibitory. The present study aims to explore the molecular mechanisms induced by NGF in glioma cancer cells.

Methods

The effects of NGF were investigated in high grade glioma and low grade pediatric glioma (PLGG) cell lines through comparative studies. In particular, we investigated TrkA‐mediated cellular pathways, molecular signaling, proliferation, cell cycle and cellular senescence.

Results

We found that exposure of PLGG cells to NGF produced stable growth arrest with the features of a senescence phenotype but without the expression of anti‐poly(ADP‐ribose) polymerase cleavage, a marker of apoptosis. Moreover, NGF treatment promoted the phosphorylation of extracellular signal‐regulated kinase1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) signaling. In addition, K252a, a TrkA inhibitor, significantly reduced the phosphorylation of the aforementioned signaling pathways, suggesting that NGF‐activated ERK1/2 and AKT signaling take place downstream of TrkA‐neurotrophin interaction.

Conclusions

These findings provide the first evidence that NGF can induce senescence of PLGG cells in a receptor‐mediated fashion, thus supporting the hypothesis that in the clinical setting NGF might be beneficial to pediatric glioma patients.
Estrogen deprivation aggravates intracellular calcium dyshomeostasis in the heart of obese‐insulin resistant rats
Authors: Palee Siripong , Minta Wanitchaya , Mantor Duangkamol , Sutham Wissuta , Kerdphoo Sasiwan , Pratchayasakul Wasana , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: November 2018

The incidence of cardiovascular disease and metabolic syndrome increases after the onset of menopause, giving evidence for the vital role of estrogen. Intracellular calcium [Ca2+]i regulation plays an important role in the maintenance of left ventricular (LV) contractile function. Although either estrogen deprivation or obesity has been shown to strongly affect the metabolic status and LV function, the effects of estrogen deprivation on the cardiometabolic status and cardiac [Ca
2+]i regulation in the obese‐insulin resistant condition have never been investigated. Our hypothesis was that estrogen deprivation aggravates LV dysfunction through the increased impairment of [Ca
2+]i homeostasis in obese‐insulin resistant rats. Female rats were fed on either a high‐fat (HFD, 59.28% fat) or normal (ND, 19.77% fat) diet for 13 weeks. Then, rats were divided into sham (HFS and NDS) operated or ovariectomized (HFO and NDO) groups. Six weeks after surgery, metabolic status, LV function and incidence of [Ca
2+]i transients were determined. NDO, HFS, and HFO rats had evidence of obese‐insulin resistance indicated by increased body weight with hyperinsulinemia and euglycemia. Although NDO, HFS, and HFO rats had markedly reduced %LV fractional shortening, E/A ratio and decreased [Ca
2+]i transient amplitude and decay rate, HFO rats had the most severe impairments. These findings indicate that estrogen deprivation had a strong impact on abnormal LV function through [Ca
2+]i regulation. In addition, evidence was found that in obese‐insulin resistant rats, estrogen deprivation severely aggravates LV dysfunction via increased impairment of [Ca
2+]i homeostasis.
Long‐term evaluation of corneal sub‐basal nerve recovery after photorefractive keratectomy and influence of pars plana vitrectomy
Authors: Tosi Gian Marco , Martone Gianluca , Bacci Tommaso , Tarantello Antonio , Baiocchi Stefano , Marigliani Davide , Cevenini Gabriele , Menicacci Flavia , Virgili Gianni , Massaro‐Giordano Giacomina
Published: November 2018

The corneal sub‐basal nerve (SBN) plexus is destroyed during photorefractive keratectomy (PRK) and its recovery is still a matter of debate. In vivo confocal microscopy (IVCM) was used to evaluate SBN plexus in 23 patients at a distance of 10–25 years (mean 15.6 years) from myopic PRK. Because 8 out of the 23 PRK patients underwent pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment, IVCM was also performed on those patients 6 months after PPV. Thirteen patients matched for age and myopia served as controls (non‐PRK). SBN plexus was markedly reduced after PRK compared with non‐PRK eyes and showed a slow, continuous but incomplete recovery up to the end of our follow‐up (range 10–25 years). PRK and non‐PRK eyes showed a marked reduction in SBN density 6 months after PPV, thus demonstrating a detrimental effect exerted by PPV on SBN plexus.
Mitochondrial quality control in cardiac cells: Mechanisms and role in cardiac cell injury and disease
Authors: Tahrir Farzaneh G. , Langford Dianne , Amini Shohreh , Mohseni Ahooyi Taha , Khalili Kamel
Published: November 2018

Mitochondria play an important role in maintaining cardiac homeostasis by supplying the major energy required for cardiac excitation–contraction coupling as well as controlling the key intracellular survival and death pathways. Healthy mitochondria generate ATP molecules through an aerobic process known as oxidative phosphorylation (OXPHOS). Mitochondrial injury during myocardial infarction (MI) impairs OXPHOS and results in the excessive production of reactive oxygen species (ROS), bioenergetic insufficiency, and contributes to the development of cardiovascular diseases. Therefore, mitochondrial biogenesis along with proper mitochondrial quality control machinery, which removes unhealthy mitochondria is pivotal for mitochondrial homeostasis and cardiac health. Upon damage to the mitochondrial network, mitochondrial quality control components are recruited to segregate the unhealthy mitochondria and target aberrant mitochondrial proteins for degradation and elimination. Impairment of mitochondrial quality control and accumulation of abnormal mitochondria have been reported in the pathogenesis of various cardiac disorders and heart failure. Here, we provide an overview of the recent studies describing various mechanistic pathways underlying mitochondrial homeostasis with the main focus on cardiac cells. In addition, this review demonstrates the potential effects of mitochondrial quality control dysregulation in the development of cardiovascular disease.
Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia‐reperfusion injury through inhibition of miR‐146a‐5p expression
Authors: Shu Liliang , Zhang Wanzhe , Huang Gongcheng , Huang Chen , Zhu Xiaohua , Su Gang , Xu Jing
Published: November 2018

The aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia‐reperfusion (I/R) injury. Hypoxia/reoxygenation (H/R) model in neonatal rat cardiomyocytes, and I/R model in rats, were established following troxerutin preconditioning. The quantitative real‐time polymerase chain reaction analysis was performed to examine the messenger RNA miR‐146a‐5p expression in cardiomyocytes and myocardial tissues. Hemodynamic parameters and serum creatine kinase, lactate dehydrogenase, tumor necrosis factor‐α, and interleukin‐10 were evaluated. Infarct size was examined by 2,3,5‐triphenyltetrazolium chloride staining. Besides, myocardial apoptosis was detected by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the protein levels of caspase‐3, Bax, and Bcl‐2. The results showed that, troxerutin decreased rat cardiomyocyte apoptosis during H/R injury. Furthermore, the antiapoptotic effect of troxerutin against I/R injury was mediated by miR‐146a‐5p downregulation. In vivo experiments suggested that troxerutin alleviated myocardial I/R injury in rats via inhibition of miR‐146a‐5p. In conclusion, troxerutin exerted cardioprotective effects during I/R injury by downregulating miR‐146a‐5p.
A comparison of three strategies for biopanning of phage‐scFv library against diphtheria toxin
Authors: Lakzaei Mostafa , Rasaee Mohhamad Javad , Fazaeli Ali Akbar , Aminian Mahdi
Published: November 2018

The biopanning process is a critical step in phage display for isolating peptides or proteins with specific binding properties. Conventional panning methods are sometimes not so effective and may result in nonspecific or low‐yield positive results. In this study, three different strategies including soluble antibody‐capturing, pH‐stepwise elution, and conventional panning were used for enrichment of specific clones against diphtheria toxoid. The reactivity of the selected clones was evaluated using an indirect enzyme‐linked immunosorbent assay. The positive clones were screened using Vero cell viability assay. The neutralizing clones were expressed in HB2151 strain of Escherichia coli and soluble single‐chain fragment variable (scFv) fragments were purified by nickel‐nitrilotriacetic acid affinity chromatography. Finally, the ability of scFv fragments for neutralizing diphtheria toxin (DT) were evaluated again using Vero cell viability assay. After four rounds of panning, the soluble antibody‐capturing method yielded 15 positive phage‐scFv clones against diphtheria toxoid. Conventional panning and pH‐stepwise elution model resulted from nine and five positive phage‐scFv clones, respectively. Among all positive clones, three clones were able to neutralize DT in Vero cell viability assay. Two of these clones belonged to a soluble antibody‐capturing method and one of them came from conventional panning. Three neutralizing clones were used for soluble expression and purification of scFvs fragments. It was found that these soluble scFv fragments possessed neutralizing activity ranging from 0.15 to 0.6 µg against two‐fold cytotoxic dose 99% of DT. In conclusion, the results of our study indicate that soluble antibody‐capturing method is an efficient method for isolation of specific scFv fragments.
Aβ stimulates microglial activation through antizyme‐dependent downregulation of ornithine decarboxylase
Authors: Cheng Yu‐Wen , Chang Chun‐Cheng , Chang Ti‐Sheng , Li Hsin‐Hua , Hung Hui‐Chih , Liu Guang‐Yaw , Lin Chih‐Li
Published: November 2018

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Its pathology is associated with the deposition of amyloid β (Aβ), an abnormal extracellular peptide. Moreover, its pathological progression is closely accompanied by neuroinflammation. Specifically, Aβ‐associated microglial overactivation may have the central role in AD pathogenesis. Interestingly, arginine metabolism may contribute to the equilibrium between M1 and M2 microglia. However, little is known about the involvement of arginine metabolism in Aβ‐induced microglial neuroinflammation and neurotoxicity. Moreover, the underlying mechanism by which Aβ induces the transition of microglia to the M1 phenotype remains unclear. In this study, we investigated the role of Aβ in mediating microglial activation and polarization both in vitro and in vivo. Our results demonstrated that under the Aβ treatment, ornithine decarboxylase (ODC), a rate‐limiting enzyme in the regulation of arginine catabolism, regulates microglial activation by altering the antizyme (AZ) + 1 ribosomal frameshift. Furthermore, the restoration of ODC protein expression levels has profound effects on inhibition of Aβ‐induced M1 markers and thus attenuates microglial‐mediated cytotoxicity. Altogether, our findings suggested that Aβ may contribute to M1‐like activation by disrupting the balance between ODC and AZ in microglia.
Prognostic value of a gene signature in clear cell renal cell carcinoma
Authors: Chen Liang , Luo Yongwen , Wang Gang , Qian Kaiyu , Qian Guofeng , Wu Chin‐Lee , Dan Han C. , Wang Xinghuan , Xiao Yu
Published: November 2018

Renal cancer is a common urogenital system malignance. Novel biomarkers could provide more and more critical information on tumor features and patients’ prognosis. Here, we performed an integrated analysis on the discovery set and established a three‐gene signature to predict the prognosis for clear cell renal cell carcinoma (ccRCC). By constructing a LASSO Cox regression model, a 3‐messenger RNA (3‐mRNA) signature was identified. Based on the 3‐mRNA signature, we divided patients into high‐ and low‐risk groups, and validated this by using three other data sets. In the discovery set, this signature could successfully distinguish between the high‐ and low‐risk patients (hazard ratio (HR), 2.152; 95% confidence interval (CI),1.509–3.069; p < 0.0001). Analysis of internal and two external validation sets yielded consistent results (internal: HR, 2.824; 95% CI, 1.601–4.98;
p < 0.001; GSE29609: HR, 3.002; 95% CI, 1.113–8.094;
p = 0.031; E‐MTAB‐3267: HR, 2.357; 95% CI, 1.243–4.468;
p = 0.006). Time‐dependent receiver operating characteristic (ROC) analysis indicated that the area under the ROC curve at 5 years was 0.66 both in the discovery and internal validation set, while the two external validation sets also suggested good performance of the 3‐mRNA signature. Besides that, a nomogram was built and the calibration plots and decision curve analysis indicated the good performance and clinical utility of the nomogram. In conclusion, this 3‐mRNA classifier proved to be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients.